Trial Outcomes & Findings for M7824 in Subjects With HPV Associated Malignancies (NCT NCT03427411)

NCT ID: NCT03427411

Last Updated: 2023-03-28

Results Overview

The percentage of participants that achieved an objective confirmed complete or partial overall tumor response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 57 participants
• Primary outcome timeframe: Every six weeks for up to one year
• Results posted on: 2023-03-28

Participant Flow

Participant milestones

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Overall Study STARTED	30	27
Overall Study COMPLETED	30	26
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Overall Study Screen failure - platelets too low	0	1

Baseline Characteristics

M7824 in Subjects With HPV Associated Malignancies

Baseline characteristics by cohort

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=30 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=27 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Total n=57 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	18 Participants n=7 Participants	43 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Age, Continuous	53.48 years STANDARD_DEVIATION 13.49 • n=5 Participants	58.73 years STANDARD_DEVIATION 11.94 • n=7 Participants	55.96 years STANDARD_DEVIATION 12.94 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	11 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	16 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants	25 Participants n=7 Participants	53 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	26 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	27 participants n=7 Participants	57 participants n=5 Participants
Site of Primary Tumor Anus	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Site of Primary Tumor Cervix	15 Participants n=5 Participants	6 Participants n=7 Participants	21 Participants n=5 Participants
Site of Primary Tumor Head-face or neck - Not Otherwise Specified	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Site of Primary Tumor Head/Neck	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Site of Primary Tumor Hypopharynx	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Site of Primary Tumor Oropharynx	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Site of Primary Tumor Rectum	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Site of Primary Tumor Tongue	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Site of Primary Tumor Tongue, Base of Tongue	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Site of Primary Tumor Tonsil	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Site of Primary Tumor Vagina	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Site of Primary Tumor Vulva	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Site of Primary Tumor Penile	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every six weeks for up to one year

Population: 1/30 participants was not evaluable in the naïve group because the participant was determined to be HPV negative. 1/27 was not evaluable in the refractory group because one participant was a screen failure and was not treated.

The percentage of participants that achieved an objective confirmed complete or partial overall tumor response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=29 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Percentage of Participants That Achieved an Objective Confirmed Complete or Partial Overall Tumor Response	31 percentage of participants Interval 15.3 to 50.8	7.7 percentage of participants Interval 0.9 to 25.1

SECONDARY outcome

Timeframe: Time from the date of first treatment to the date of disease progression or death, up to 12 months

Population: 1/30 participants was not evaluable in the naïve group because they were found to be HPV negative and 1/27 was not evaluable in the refractory group because one participant was a screen failure.

PFS is defined as the time from the date of first treatment to the date of disease progression or death. Progression was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and is defined as at least a 20% increase in the sum of diameters of target lesions, or appearance of one or more new lesions.

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=29 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Progression-free Survival Time (PFS)	3.5 Months Interval 1.5 to 7.4	1.4 Months Interval 0.0 to 9.2

SECONDARY outcome

Timeframe: 6 months

Population: 1/30 participants was not evaluable in the naïve group because they were determined to be HPV negative, and 1/27 was not evaluable in the refractory group because one participant was a screen failure.

The percentage of participants with disease control who achieved a complete response, partial response and stable disease lasting at least 6 months was measured by the response evaluation criteria in solid tumors (RECIST)version 1.1. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) (at least a 20% increase in the sum of diameters of target lesions, or appearance of one or more new lesions).

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=29 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Percentage of Participants With Disease Control Who Achieved a Complete Response, Partial Response and Stable Disease Defined by the Response Evaluation Criteria in Solid Tumors (RECIST)Version 1.1 Lasting at Least 6 Months	62.1 percentage of participants Interval 42.3 to 79.3	19.2 percentage of participants Interval 6.6 to 39.4

SECONDARY outcome

Timeframe: Time from the date of first treatment to the date of death, up to 3 years.

Population: 1/30 participants was not evaluable in the naïve group because the patient was determined to be HPV negative, and 1/27 was not evaluable in the refractory group because one participant was a screen failure and was not treated.

OS is defined as the time from the date of first treatment to the date of death and was measured by Kaplan-Meier analysis.

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=29 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Overall Survival (OS)	19.2 Months Interval 9.7 to The upper limit of the confidence interval cannot be estimated because several participants are still alive.	4.4 Months Interval 2.7 to 13.2

SECONDARY outcome

Timeframe: 28 days after treatment

Population: One participant enrolled in the refractory group was a screen failure and was not treated.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events version 5.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=30 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Number of Participants With Serious Grade ≥3 Adverse Events Considered Related to Study Treatment of M7824	6 Participants	4 Participants

SECONDARY outcome

Timeframe: median of 2 years

Population: Only cohorts 1 and 2 was evaluable for this outcome measure.

Response based on adequate similarity defined as P-value > 0.2 with Fisher's exact test of results in cohorts 1 and 2 was compared with a two-sided Fishers exact test, and response was measured by the response evaluation criteria in solid tumors (RECIST)version 1.1. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease is at least a 20% increase in the sum of diameters of target lesions, or appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=29 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Number of Checkpoint Inhibitor Naive Participants With Response Based on Adequate Similarity (Defined as P-value > 0.2 With Fisher's Exact Test) of Results in Cohorts 1 and 2 Complete Response	2 Participants	—
Number of Checkpoint Inhibitor Naive Participants With Response Based on Adequate Similarity (Defined as P-value > 0.2 With Fisher's Exact Test) of Results in Cohorts 1 and 2 Partial Response	7 Participants	—
Number of Checkpoint Inhibitor Naive Participants With Response Based on Adequate Similarity (Defined as P-value > 0.2 With Fisher's Exact Test) of Results in Cohorts 1 and 2 Progressive Disease	10 Participants	—
Number of Checkpoint Inhibitor Naive Participants With Response Based on Adequate Similarity (Defined as P-value > 0.2 With Fisher's Exact Test) of Results in Cohorts 1 and 2 Stable Disease	9 Participants	—
Number of Checkpoint Inhibitor Naive Participants With Response Based on Adequate Similarity (Defined as P-value > 0.2 With Fisher's Exact Test) of Results in Cohorts 1 and 2 Not Evaluable	1 Participants	—

SECONDARY outcome

Timeframe: Up to 30 days from last treatment

Population: One participant enrolled in the refractory group was a screen failure and was not treated.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Disease progression is at least a 20% increase in the sum of diameters of target lesions, or appearance of one or more new lesions measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=30 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Percentage of Participants That Were Hospitalized Because of Adverse Events Attributed to Disease Progression	37.9 percentage of participants	69.2 percentage of participants

SECONDARY outcome

Timeframe: Time from complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is objectively documented, up to 12 months

Duration of response is defined as the time from complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is objectively documented. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progression is at least a 20% increase in the sum of diameters of target lesions, or appearance of one or more new lesions.

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=9 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=2 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Duration of Response (Complete Response or Partial Response)	NA Months Interval 8.3 to Median and upper end of the confidence interval cannot be estimated because duration of response was censored at the time of data cut off in 6/9 responders since these 6 participants have not had disease recurrence and therefore did not have a duration of response. The other 20 participants on this cohort were not assessed for duration of response as they did not have a response to begin with. Therefore median duration of response and upper end of the confidence interval cannot be calculated.	4.0 Months Interval 2.8 to The upper end of the confidence interval cannot be estimated because of the low number of responding participants (n=2) assessed for duration of response in this cohort. In addition, the other 24 participants on this cohort were not assessed for duration of response as they did not have a response to begin with. Therefore the upper end of the confidence interval cannot be calculated.

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group.

Population: One enrolled participant was a screen failure and was not treated.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=30 Participants Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 Participants Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	30 Participants	26 Participants

Adverse Events

Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks

Serious events: 19 serious events

Other events: 30 other events

Deaths: 18 deaths

Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks

Serious events: 21 serious events

Other events: 26 other events

Deaths: 22 deaths

Serious adverse events

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=30 participants at risk Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 participants at risk Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, brain metastasis	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Abdominal distension	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Abdominal pain	10.0% 3/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Acute kidney injury	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Alanine aminotransferase increased	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Alkaline phosphatase increased	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Blood and lymphatic system disorders Anemia	10.0% 3/30 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 12 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Ascites	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Aspartate aminotransferase increased	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Atrial fibrillation	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Atrial flutter	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Hepatobiliary disorders Bile duct stenosis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Blood bilirubin increased	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Bronchial infection	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Hepatobiliary disorders Cholecystitis	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Confusion	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Death Not Otherwise Specified (NOS)	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Dehydration	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Depressed level of consciousness	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Diarrhea	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Disease progression	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	19.2% 5/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Dizziness	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Esophagitis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Fall	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Fatigue	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Fever	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Fracture	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Fungemia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Hematuria	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Hepatobiliary disorders Hepatobiliary disorders - Other, Hepatic duct stenosis	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Hepatobiliary disorders Hepatobiliary disorders - Other, Nodular Regenerative Hyperplasia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Hepatobiliary disorders Hepatobiliary disorders - Other, left hepatic lobe abscesses	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypercalcemia	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyperglycemia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypokalemia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Hypotension	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Ileus	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Ischemia cerebrovascular	3.3% 1/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Myocarditis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Myositis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Nausea	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Disease progression	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Nervous system disorders - Other, Vocal fold paralysis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Nervous system disorders - Other, balance difficulties	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Pain	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Paresthesia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Hepatobiliary disorders Portal vein thrombosis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Presyncope	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Renal and urinary disorders - Other, Specify	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Sepsis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Sinus tachycardia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Small intestinal obstruction	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Spinal cord compression	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, Left Psoas Mass Resection	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, Nephrostomy tube exchange trauma	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, Resection abdominal (abd) wall mets	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, Resection abd wall mets w/abd wall reconstruction	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, TAVR aortic valve replacement	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, craniotomy for resection of cerebellar tumors	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, specify	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, radiation therapy for cerebellar tumor	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, surgery to stabilize leg bone metastasis	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Thromboembolic event	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Tracheal obstruction	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Urinary tract infection	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Urinary tract obstruction	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Urinary tract pain	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Reproductive system and breast disorders Vaginal hemorrhage	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Voice alteration	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Vomiting	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.

Other adverse events

Measure	Participants Naïve to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=30 participants at risk Participants with anal cancer, non-neuroendocrine cervical cancer, P16 positive (P16+) oropharyngeal cancers, and other rare HPV associated tumors (e.g., squamous cell rectal, vulvar, vaginal, penile cancer, neuroendocrine cervical) naïve to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.	Participants Refractory to Checkpoint Inhibition - M7824 1,200 mg Intravenous Once Every 2 Weeks n=26 participants at risk Participants with human papillomavirus (HPV) associated cancers refractory to checkpoint inhibition treated with M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks until confirmed progressive disease, death, unacceptable toxicity, or study withdrawal.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gastrointestinal disorders - Other, Hyperpigmentation of tongue	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gingival pain	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Hallucinations	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Headache	30.0% 9/30 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Hearing impaired	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Hematuria	16.7% 5/30 • Number of events 8 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Hemorrhoidal hemorrhage	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Herpes simplex reactivation	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Hot flashes	16.7% 5/30 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyperglycemia	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyperkalemia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyperphosphatemia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Hypertension	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Endocrine disorders Hyperthyroidism	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypoalbuminemia	23.3% 7/30 • Number of events 9 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	30.8% 8/26 • Number of events 8 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypocalcemia	13.3% 4/30 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypokalemia	23.3% 7/30 • Number of events 14 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypomagnesemia	10.0% 3/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hyponatremia	10.0% 3/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 12 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Hypophosphatemia	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 11 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Hypotension	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Endocrine disorders Hypothyroidism	23.3% 7/30 • Number of events 8 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations INR increased	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Infections and infestations - Other, Specify	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Infusion related reaction	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Insomnia	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Intestinal stoma site bleeding	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Joint effusion	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Lethargy	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Libido decreased	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Lipase increased	3.3% 1/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Lung infection	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Lymphedema	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Lymphocyte count decreased	36.7% 11/30 • Number of events 22 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	46.2% 12/26 • Number of events 27 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Memory impairment	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Movements involuntary	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Mucosal infection	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Mucositis oral	13.3% 4/30 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Muscle cramp	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, TMJ symptoms, Left jaw	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, partial tendon rupture	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Myalgia	13.3% 4/30 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Myocarditis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Myositis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Nail infection	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Nausea	36.7% 11/30 • Number of events 18 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	30.8% 8/26 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Neck pain	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Brain lesion	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Keratoacanthomas	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Keratoacanthoma	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Nervous system disorders - Other, Specify	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Nervous system disorders - Other, balance difficulties	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Neutrophil count decreased	10.0% 3/30 • Number of events 16 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Non-cardiac chest pain	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Oral hemorrhage	30.0% 9/30 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 9 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Oral pain	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Pain	20.0% 6/30 • Number of events 9 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Pain in extremity	10.0% 3/30 • Number of events 7 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 7 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Palpitations	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Papulopustular rash	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Paresthesia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Reproductive system and breast disorders Pelvic pain	6.7% 2/30 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Pericardial effusion	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Reproductive system and breast disorders Perineal pain	3.3% 1/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Peripheral motor neuropathy	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Platelet count decreased	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 8 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Hepatobiliary disorders Portal vein thrombosis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Presyncope	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Pruritus	26.7% 8/30 • Number of events 14 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	30.8% 8/26 • Number of events 16 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Psychosis	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Rash acneiform	33.3% 10/30 • Number of events 17 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Rash maculo-papular	30.0% 9/30 • Number of events 16 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Rash pustular	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Rectal hemorrhage	20.0% 6/30 • Number of events 11 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Rectal pain	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Renal and urinary disorders - Other, Specify	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Renal and urinary disorders - Other, Hydronephrosis-moderate, L-sided	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Renal and urinary disorders - Other, Urinary hesitancy and sensation of incomplete voiding	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Renal and urinary disorders - Other, Urinary frequency	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, Specify	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Restlessness	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Eye disorders Retinopathy	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Serum amylase increased	3.3% 1/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Sinus tachycardia	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	26.9% 7/26 • Number of events 7 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, seborrheic dermatitis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Skin infection	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Skin papilloma	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Skin ulceration	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Small intestinal obstruction	3.3% 1/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Somnolence	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Sore throat	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Stridor	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Supraventricular tachycardia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, inguinal hernia	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Surgical and medical procedures Surgical and medical procedures - Other, surgical de-bulking condyloma	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Thromboembolic event	13.3% 4/30 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Tinnitus	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Upper respiratory infection	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Urinary frequency	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Urinary retention	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Urinary tract infection	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Urinary tract obstruction	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Urinary urgency	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Urticaria	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Reproductive system and breast disorders Uterine hemorrhage	3.3% 1/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Reproductive system and breast disorders Vaginal hemorrhage	10.0% 3/30 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Eye disorders Vision decreased	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Vomiting	26.7% 8/30 • Number of events 12 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	30.8% 8/26 • Number of events 11 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Weight gain	6.7% 2/30 • Number of events 7 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Weight loss	20.0% 6/30 • Number of events 14 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	26.9% 7/26 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Wheezing	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations White blood cell decreased	10.0% 3/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Wound dehiscence	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Abdominal pain	26.7% 8/30 • Number of events 11 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	26.9% 7/26 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Endocrine disorders Adrenal insufficiency	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Agitation	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Alanine aminotransferase increased	13.3% 4/30 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Alkaline phosphatase increased	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Immune system disorders Allergic reaction	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Alopecia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Anal hemorrhage	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Blood and lymphatic system disorders Anemia	63.3% 19/30 • Number of events 44 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	73.1% 19/26 • Number of events 53 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Anorexia	33.3% 10/30 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	46.2% 12/26 • Number of events 16 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Anosmia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Anxiety	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Arthralgia	3.3% 1/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Ascites	10.0% 3/30 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Aspartate aminotransferase increased	13.3% 4/30 • Number of events 8 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Atrial fibrillation	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Cardiac disorders Atrial flutter	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Back pain	20.0% 6/30 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Bacteremia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Bladder spasm	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Bloating	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Blood bilirubin increased	3.3% 1/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Eye disorders Blurred vision	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Bone pain	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Infections and infestations Bronchial infection	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Bullous dermatitis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations CPK increased	3.3% 1/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Cardiac troponin I increased	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Chills	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Colitis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Colonic obstruction	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Concentration impairment	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Confusion	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Constipation	33.3% 10/30 • Number of events 11 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	23.1% 6/26 • Number of events 7 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Cough	30.0% 9/30 • Number of events 12 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	19.2% 5/26 • Number of events 8 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Creatinine increased	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Renal and urinary disorders Cystitis noninfective	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Death NOS	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Metabolism and nutrition disorders Dehydration	10.0% 3/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	26.9% 7/26 • Number of events 8 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Delirium	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Psychiatric disorders Depression	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Dermatitis radiation	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Diarrhea	30.0% 9/30 • Number of events 16 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Dizziness	13.3% 4/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	19.2% 5/26 • Number of events 6 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Eye disorders Dry eye	3.3% 1/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Dry mouth	6.7% 2/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Dry skin	3.3% 1/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Duodenal obstruction	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Dysgeusia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Dyspepsia	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Dysphagia	10.0% 3/30 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Dyspnea	36.7% 11/30 • Number of events 14 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	42.3% 11/26 • Number of events 14 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, Continuous drainage L ear; hospitalized	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, Intermittent bloody discharge L ear	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, Specify	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, Left ear fullness/congestion-ENT consult ordered	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, fullness/congestion left ear	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Ear and labyrinth disorders Ear pain	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Edema face	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Edema limbs	26.7% 8/30 • Number of events 9 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Investigations Electrocardiogram QT corrected interval prolonged	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Respiratory, thoracic and mediastinal disorders Epistaxis	26.7% 8/30 • Number of events 10 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	15.4% 4/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Skin and subcutaneous tissue disorders Erythroderma	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Esophagitis	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Extrapyramidal disorder	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Eye disorders Eye disorders - Other, peripheral visual fields altered left eye, r/t brain lesion	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Facial muscle weakness	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Nervous system disorders Facial nerve disorder	3.3% 1/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Fall	10.0% 3/30 • Number of events 5 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Fatigue	60.0% 18/30 • Number of events 32 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	42.3% 11/26 • Number of events 14 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Fecal incontinence	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Fever	23.3% 7/30 • Number of events 11 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Eye disorders Flashing lights	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Flatulence	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Flu like symptoms	20.0% 6/30 • Number of events 7 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Vascular disorders Flushing	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Injury, poisoning and procedural complications Fracture	6.7% 2/30 • Number of events 4 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
General disorders Gait disturbance	6.7% 2/30 • Number of events 2 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gastric ulcer	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gastritis	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gastroesophageal reflux disease	3.3% 1/30 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gastrointestinal disorders - Other, Diverticulosis	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.
Gastrointestinal disorders Gastrointestinal disorders - Other, Esophageal erosions	0.00% 0/30 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 42 months and 28 days for the naïve group, and 40 months and 16 days for the refractory group. One participant enrolled in the refractory group was a screen failure and was not treated.

Additional Information

Dr. Julius Strauss

National Cancer Institute

Phone: 240-858-3999

Email: julius.strauss@nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place