Trial Outcomes & Findings for Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (NCT NCT04287868)

Last Updated: 2025-04-13

Results Overview

BOR is defined as a complete response or partial response assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

51 participants

Primary outcome timeframe

Every 2 months, up to approximately 10 months

Results posted on

2025-04-13

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies Cohort 1, Arm 1, Treatment Assignment Code (TAC) 1: Participants with HPV associated malignancies will receive human papillomavirus (HPV) vaccine every (q) 4 weeks x6, then q3 months (MO) x2 + NHS-IL12 q 4 weeks (wks) + M7824 q 2 wks. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.	Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy Cohort 2, Arm 2, Treatment Assignment Code (TAC) 1: Participants with cervical cancer with prior pelvic radiation and boost brachytherapy will receive human papillomavirus (HPV) vaccine + NHS-IL12 + M7824 (MSB0011359C) at reduced doses. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.
Overall Study STARTED	48	3
Overall Study COMPLETED	47	3
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies Cohort 1, Arm 1, Treatment Assignment Code (TAC) 1: Participants with HPV associated malignancies will receive human papillomavirus (HPV) vaccine every (q) 4 weeks x6, then q3 months (MO) x2 + NHS-IL12 q 4 weeks (wks) + M7824 q 2 wks. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.	Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy Cohort 2, Arm 2, Treatment Assignment Code (TAC) 1: Participants with cervical cancer with prior pelvic radiation and boost brachytherapy will receive human papillomavirus (HPV) vaccine + NHS-IL12 + M7824 (MSB0011359C) at reduced doses. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.
Overall Study Screening fail	1	0

Baseline Characteristics

Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies n=48 Participants Cohort 1, Arm 1, Treatment Assignment Code (TAC) 1: Participants with HPV associated malignancies will receive human papillomavirus (HPV) vaccine every (q) 4 weeks x6, then q3 months (MO) x2 + NHS-IL12 q 4 weeks (wks) + M7824 q 2 wks. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.	Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy n=3 Participants Cohort 2, Arm 2, Treatment Assignment Code (TAC) 1: Participants with cervical cancer with prior pelvic radiation and boost brachytherapy will receive human papillomavirus (HPV) vaccine + NHS-IL12 + M7824 (MSB0011359C) at reduced doses. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.	Total n=51 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	37 Participants n=5 Participants	3 Participants n=7 Participants	40 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	57.54 years STANDARD_DEVIATION 10.72 • n=5 Participants	51.17 years STANDARD_DEVIATION 19.55 • n=7 Participants	57.16 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	3 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	0 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	2 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants	2 Participants n=7 Participants	39 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	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	48 participants n=5 Participants	3 participants n=7 Participants	51 participants n=5 Participants

PRIMARY outcome

Timeframe: Every 2 months, up to approximately 10 months

Population: 48 participants were screened for Cohort (C)1, 1 was a screen fail =\> 47 were treated on C1. 3 participants were screened for C2 and were treated on it. 50 participants (47 in C1 and 3 in C2) comprise the complete treated population ("All participants"). As pre-specified by the protocol cohort 2 is not required to be reported independently.

Outcome measures

Outcome measures
Measure	All Participants n=50 Participants Participants with Human Papillomavirus Associated Malignancies (N = 50, 47 from Cohort 1, 3 from Cohort 2)	Participants With Human Papillomavirus 16 (HPV16+) Tumors n=37 Participants Participants with Human Papillomavirus 16 Tumors (HPV16+) from both Cohort 1 and Cohort 2 further stratified by prior immune checkpoint blockade. (N=37; 34 from Cohort 1, 3 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive n=8 Participants Participants with tumor testing positive for HPV16 and no previous exposure to an immune checkpoint blockade agent. (N= 8; 7 from Cohort 1, 1 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant n=29 Participants Participants with tumor testing positive for HPV16 and disease progression following prior treatment with immune checkpoint blockade agent. (N= 29; 27 from Cohort 1, 2 from Cohort 2)
Best Overall Response (BOR) in Checkpoint Naive and Immune Checkpoint Blockade (ICB) Resistant Disease in Participants With Advanced or Metastatic Human Papillomavirus (HPV) Associated Malignancies Complete Response	4 Participants	4 Participants	2 Participants	2 Participants
Best Overall Response (BOR) in Checkpoint Naive and Immune Checkpoint Blockade (ICB) Resistant Disease in Participants With Advanced or Metastatic Human Papillomavirus (HPV) Associated Malignancies Partial Response	7 Participants	7 Participants	3 Participants	4 Participants
Best Overall Response (BOR) in Checkpoint Naive and Immune Checkpoint Blockade (ICB) Resistant Disease in Participants With Advanced or Metastatic Human Papillomavirus (HPV) Associated Malignancies Overall Response rate (CR+PR)	11 Participants	11 Participants	5 Participants	6 Participants

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 34 months and 20 days.

Population: Pre-specified in the protocol for cohort 1 only. 1/48 participants in cohort 1 was a screening fail.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	All Participants n=47 Participants Participants with Human Papillomavirus Associated Malignancies (N = 50, 47 from Cohort 1, 3 from Cohort 2)	Participants With Human Papillomavirus 16 (HPV16+) Tumors Participants with Human Papillomavirus 16 Tumors (HPV16+) from both Cohort 1 and Cohort 2 further stratified by prior immune checkpoint blockade. (N=37; 34 from Cohort 1, 3 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive Participants with tumor testing positive for HPV16 and no previous exposure to an immune checkpoint blockade agent. (N= 8; 7 from Cohort 1, 1 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant Participants with tumor testing positive for HPV16 and disease progression following prior treatment with immune checkpoint blockade agent. (N= 29; 27 from Cohort 1, 2 from Cohort 2)
Number of Participants With Grades 1, 2, 3, 4 and/or 5 Treatment Related Adverse Events Grade 1	45 Participants	—	—	—
Number of Participants With Grades 1, 2, 3, 4 and/or 5 Treatment Related Adverse Events Grade 2	42 Participants	—	—	—
Number of Participants With Grades 1, 2, 3, 4 and/or 5 Treatment Related Adverse Events Grade 3	25 Participants	—	—	—
Number of Participants With Grades 1, 2, 3, 4 and/or 5 Treatment Related Adverse Events Grade 4	1 Participants	—	—	—
Number of Participants With Grades 1, 2, 3, 4 and/or 5 Treatment Related Adverse Events Grade 5	0 Participants	—	—	—

SECONDARY outcome

Timeframe: PFS is defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurs first

PFS is defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurs first. Participants who do not have disease progression or have not died at the end of follow up will be censored at the last known date the participant was progression free. Progression was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progressive disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The time from the date of first treatment to the date of death (any cause)

OS will be evaluated using Kaplan-Meier methods and is defined as the time from the date of first treatment to the date of death (any cause). Participants who are alive at the end of follow up will be censored at the last known date alive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: While participant on study; an average of 3 months

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progressive disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

Outcome measures

Outcome measures
Measure	All Participants n=47 Participants Participants with Human Papillomavirus Associated Malignancies (N = 50, 47 from Cohort 1, 3 from Cohort 2)	Participants With Human Papillomavirus 16 (HPV16+) Tumors n=3 Participants Participants with Human Papillomavirus 16 Tumors (HPV16+) from both Cohort 1 and Cohort 2 further stratified by prior immune checkpoint blockade. (N=37; 34 from Cohort 1, 3 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive Participants with tumor testing positive for HPV16 and no previous exposure to an immune checkpoint blockade agent. (N= 8; 7 from Cohort 1, 1 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant Participants with tumor testing positive for HPV16 and disease progression following prior treatment with immune checkpoint blockade agent. (N= 29; 27 from Cohort 1, 2 from Cohort 2)
Ratio of Participants That Are Hospitalized Because of Adverse Events Attributed to Disease Progression.	0.04 Proportion of participants	0 Proportion of participants	—	—

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 34 months and 20 days.

Population: Pre-specified in the protocol for cohort 2 only.

Outcome measures

Outcome measures
Measure	All Participants n=3 Participants Participants with Human Papillomavirus Associated Malignancies (N = 50, 47 from Cohort 1, 3 from Cohort 2)	Participants With Human Papillomavirus 16 (HPV16+) Tumors Participants with Human Papillomavirus 16 Tumors (HPV16+) from both Cohort 1 and Cohort 2 further stratified by prior immune checkpoint blockade. (N=37; 34 from Cohort 1, 3 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive Participants with tumor testing positive for HPV16 and no previous exposure to an immune checkpoint blockade agent. (N= 8; 7 from Cohort 1, 1 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant Participants with tumor testing positive for HPV16 and disease progression following prior treatment with immune checkpoint blockade agent. (N= 29; 27 from Cohort 1, 2 from Cohort 2)
Number of Treatment Related Grades 1, 2, 3, 4 and/or 5 Adverse Events Grade 1	3 adverse events	—	—	—
Number of Treatment Related Grades 1, 2, 3, 4 and/or 5 Adverse Events Grade 2	3 adverse events	—	—	—
Number of Treatment Related Grades 1, 2, 3, 4 and/or 5 Adverse Events Grade 3	1 adverse events	—	—	—
Number of Treatment Related Grades 1, 2, 3, 4 and/or 5 Adverse Events Grade 4	1 adverse events	—	—	—
Number of Treatment Related Grades 1, 2, 3, 4 and/or 5 Adverse Events Grade 5	0 adverse events	—	—	—

SECONDARY outcome

Timeframe: At disease progression, an average of 10 months

Population: 1/48 participants in cohort 1 was a screening fail.

DOR is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that progressive disease (PD) is objectively documented and is evaluated using the Kaplan-Meier method. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

Outcome measures

Outcome measures
Measure	All Participants n=47 Participants Participants with Human Papillomavirus Associated Malignancies (N = 50, 47 from Cohort 1, 3 from Cohort 2)	Participants With Human Papillomavirus 16 (HPV16+) Tumors n=3 Participants Participants with Human Papillomavirus 16 Tumors (HPV16+) from both Cohort 1 and Cohort 2 further stratified by prior immune checkpoint blockade. (N=37; 34 from Cohort 1, 3 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive Participants with tumor testing positive for HPV16 and no previous exposure to an immune checkpoint blockade agent. (N= 8; 7 from Cohort 1, 1 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant Participants with tumor testing positive for HPV16 and disease progression following prior treatment with immune checkpoint blockade agent. (N= 29; 27 from Cohort 1, 2 from Cohort 2)
Duration of Response (DOR)	10.6 Months Interval 3.7 to Not estimable: not enough events to estimate.	10.2 Months Confidence interval cannot be calculated for one participant.	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 34 months and 20 days.

Population: 1/48 participants in cohort 1 was a screening fail.

Here is the number of participants with serious and/or non-serious adverse events 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.

Outcome measures

Outcome measures
Measure	All Participants n=47 Participants Participants with Human Papillomavirus Associated Malignancies (N = 50, 47 from Cohort 1, 3 from Cohort 2)	Participants With Human Papillomavirus 16 (HPV16+) Tumors n=3 Participants Participants with Human Papillomavirus 16 Tumors (HPV16+) from both Cohort 1 and Cohort 2 further stratified by prior immune checkpoint blockade. (N=37; 34 from Cohort 1, 3 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive Participants with tumor testing positive for HPV16 and no previous exposure to an immune checkpoint blockade agent. (N= 8; 7 from Cohort 1, 1 from Cohort 2)	Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant Participants with tumor testing positive for HPV16 and disease progression following prior treatment with immune checkpoint blockade agent. (N= 29; 27 from Cohort 1, 2 from Cohort 2)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	47 Participants	3 Participants	—	—

Adverse Events

Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies

Serious events: 18 serious events

Other events: 47 other events

Deaths: 28 deaths

Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Charalampos Floudas

National Cancer Institute

Phone: 240-858-3032

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies n=47 participants at risk Cohort 1, Arm 1, Treatment Assignment Code (TAC) 1: Participants with HPV associated malignancies will receive human papillomavirus (HPV) vaccine every (q) 4 weeks x6, then q3 months (MO) x2 + NHS-IL12 q 4 weeks (wks) + M7824 q 2 wks. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.	Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy n=3 participants at risk Cohort 2, Arm 2, Treatment Assignment Code (TAC) 1: Participants with cervical cancer with prior pelvic radiation and boost brachytherapy will receive human papillomavirus (HPV) vaccine + NHS-IL12 + M7824 (MSB0011359C) at reduced doses. PDS0101 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0mL (2.4mg of total peptide and 3 mg of R-DOTAP (Versamune) injection). M7824 will be administered at a flat dose of 1,200 mg intravenous (IV) (over 1 hour) once every 2 weeks. NHS-IL12 will be administered by subcutaneous (SC) injection every 4 weeks.
Gastrointestinal disorders Abdominal pain	4.3% 2/47 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Investigations Alanine aminotransferase increased	2.1% 1/47 • Number of events 4 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Investigations Alkaline phosphatase increased	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Blood and lymphatic system disorders Anemia	4.3% 2/47 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Investigations Aspartate aminotransferase increased	2.1% 1/47 • Number of events 3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Infections and infestations Bacteremia	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Cardiac disorders Cardiac disorders - Other, Immune mediated myocarditis	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Investigations Creatinine increased	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Gastrointestinal disorders Duodenal hemorrhage	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Infections and infestations Enterocolitis infectious	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders Fever	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders Flu like symptoms	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Gastrointestinal disorders Gastric hemorrhage	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Gastrointestinal disorders Gastroparesis	2.1% 1/47 • Number of events 6 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders General disorders and administration site conditions - Other, Hematuria	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders General disorders and administration site conditions - Other, MUCOSAL BLEEDING, VAGINAL HEMORRHAGE;	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders General disorders and administration site conditions - Other, Mucosal bleeding	4.3% 2/47 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders General disorders and administration site conditions - Other, Mucosal bleeding (anal bleeding)	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders General disorders and administration site conditions - Other, Mucosal bleeding, vaginal	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
General disorders General disorders and administration site conditions - Other, Mucosal bleeding-Hematuria	2.1% 1/47 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Renal and urinary disorders Hematuria	4.3% 2/47 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/47 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Metabolism and nutrition disorders Hyponatremia	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Immune system disorders Immune system disorders - Other, Hemophagocytic Lymphohistiocytosis	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Infections and infestations Infections and infestations - Other, COVID	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Infections and infestations Lung infection	4.3% 2/47 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Cardiac disorders Myocardial infarction	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Gastrointestinal disorders Nausea	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.1% 1/47 • Number of events 2 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Infections and infestations Sinusitis	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Nervous system disorders Stroke	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Infections and infestations Urinary tract infection	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Renal and urinary disorders Urinary tract obstruction	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.
Gastrointestinal disorders Vomiting	2.1% 1/47 • Number of events 1 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 34 months and 20 days. 1/48 participants in cohort 1 was a screening fail.