Trial Outcomes & Findings for Phase 2 Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR (NCT NCT01854034)

NCT ID: NCT01854034

Last Updated: 2018-04-10

Results Overview

The number of participants that achieved a response to treatment as assessed by Response Evaluation Criteria is Solid Tumors (RECIST). Response is defined as having achieved either a complete response (CR) or a partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \< 10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 29 participants
• Primary outcome timeframe: From the start of treatment until the time of disease progression, median duration of follow-up of about 3 months
• Results posted on: 2018-04-10

Participant Flow

Participant milestones

Measure	AUY922 Treatment Arm AUY922 administered intravenously once a week at 70mg/m2
Overall Study STARTED	29
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	AUY922 Treatment Arm n=29 Participants AUY922 administered intravenously once a week at 70mg/m2
Age, Continuous	60 years n=29 Participants
Sex: Female, Male Female	18 Participants n=29 Participants
Sex: Female, Male Male	11 Participants n=29 Participants
Region of Enrollment United States	29 participants n=29 Participants
Median Prior Lines of Therapy	1 Therapies n=29 Participants
Number of Participants with prior EGFR TKI	6 Participants n=29 Participants
Baseline ECOG PS 0	9 Participants n=29 Participants
Baseline ECOG PS 1	18 Participants n=29 Participants
Baseline ECOG PS 2	2 Participants n=29 Participants

PRIMARY outcome

Timeframe: From the start of treatment until the time of disease progression, median duration of follow-up of about 3 months

The number of participants that achieved a response to treatment as assessed by Response Evaluation Criteria is Solid Tumors (RECIST). Response is defined as having achieved either a complete response (CR) or a partial response (PR).

• Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to < 10 mm.
• Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	AUY922 Treatment Arm n=29 Participants AUY922 administered intravenously once a week at 70mg/m2
Overall Response Rate	5 Participants

SECONDARY outcome

Timeframe: From the start of treatment until the time or death or disease progression

Overall survival (OS) is measured from the start of treatment until the time of death. Progression free survival is measured from the start of treatment until the time of death or disease progression as assessed by RECIST. Progressive disease is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression.

Outcome measures

Measure	AUY922 Treatment Arm n=29 Participants AUY922 administered intravenously once a week at 70mg/m2
Median Progression Free and Overall Survival Overall Survival	9.9 Months Interval 4.5 to 19.2
Median Progression Free and Overall Survival Progression Free Survival	2.8 Months Interval 1.3 to 5.6

SECONDARY outcome

Timeframe: From the start of treatment until 28 days after the end of treatment

The number of participants with serious adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) that were deemed to be possibly, probably, or definitely related to study treatment as determined by the treating physician.

Outcome measures

Measure	AUY922 Treatment Arm n=29 Participants AUY922 administered intravenously once a week at 70mg/m2
The Number of Participants With Treatment Related Serious Adverse Events	6 Participants

SECONDARY outcome

Timeframe: Baseline, at the time of response

The specific exon 20 epidermal growth factor receptor (EGFR) mutations among participants that achieved either a partial response or complete response as assessed by RECIST. The EGFR mutations were assessed from biopsies taken at baseline and then the baseline mutations were categorized by disease response.

• Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to < 10 mm.
• Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	AUY922 Treatment Arm n=5 Participants AUY922 administered intravenously once a week at 70mg/m2
Exon 20 EGFR Mutations Among Participants That Responded to Treatment Complete Response : D770_P772dup	1 participants
Exon 20 EGFR Mutations Among Participants That Responded to Treatment Partial Response : N771insGF	1 participants
Exon 20 EGFR Mutations Among Participants That Responded to Treatment Partial Response : D770_N771insSVD	1 participants
Exon 20 EGFR Mutations Among Participants That Responded to Treatment Partial Response : P772_H773dupPH	1 participants
Exon 20 EGFR Mutations Among Participants That Responded to Treatment Partial Response : P773dup	1 participants

Adverse Events

AUY922 Treatment Arm

Serious events: 6 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	AUY922 Treatment Arm n=29 participants at risk AUY922 administered intravenously once a week at 70mg/m2
Eye disorders Eye Disorder- Other	3.4% 1/29 • Number of events 1 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Metabolism and nutrition disorders Hypophosphatemia	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Vascular disorders Hypertension	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.

Other adverse events

Measure	AUY922 Treatment Arm n=29 participants at risk AUY922 administered intravenously once a week at 70mg/m2
Gastrointestinal disorders Abdominal pain	13.8% 4/29 • Number of events 6 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Investigations Alanine aminotransferase increased	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Immune system disorders Allergic reaction	13.8% 4/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Blood and lymphatic system disorders Anemia	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Metabolism and nutrition disorders Anorexia	31.0% 9/29 • Number of events 11 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Psychiatric disorders Anxiety	20.7% 6/29 • Number of events 6 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Arthritis	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Investigations Aspartate aminotransferase increased	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Back pain	31.0% 9/29 • Number of events 10 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Eye disorders Blurred vision	17.2% 5/29 • Number of events 5 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Bone pain	24.1% 7/29 • Number of events 10 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Buttock pain	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Eye disorders Cataract	6.9% 2/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Investigations Cholesterol high	17.2% 5/29 • Number of events 5 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Gastrointestinal disorders Constipation	24.1% 7/29 • Number of events 7 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Cough	51.7% 15/29 • Number of events 17 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Metabolism and nutrition disorders Dehydration	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Psychiatric disorders Depression	13.8% 4/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Gastrointestinal disorders Diarrhea	79.3% 23/29 • Number of events 30 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Nervous system disorders Dizziness	10.3% 3/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Gastrointestinal disorders Dry mouth	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Skin and subcutaneous tissue disorders Dry skin	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Nervous system disorders Dysgeusia	6.9% 2/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnea	48.3% 14/29 • Number of events 15 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
General disorders Edema limbs	13.8% 4/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Eye disorders Eye disorders - Other, specify	72.4% 21/29 • Number of events 33 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
General disorders Fatigue	79.3% 23/29 • Number of events 35 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
General disorders Fever	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Eye disorders Flashing lights	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Eye disorders Floaters	13.8% 4/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
General disorders Gait disturbance	13.8% 4/29 • Number of events 6 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Gastrointestinal disorders Gastroesophageal reflux disease	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	13.8% 4/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
General disorders General disorders and administration site conditions - Other, specify	17.2% 5/29 • Number of events 6 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Nervous system disorders Headache	41.4% 12/29 • Number of events 16 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Hoarseness	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Vascular disorders Hypertension	37.9% 11/29 • Number of events 23 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Metabolism and nutrition disorders Hypokalemia	6.9% 2/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Metabolism and nutrition disorders Hypomagnesemia	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Metabolism and nutrition disorders Hypophosphatemia	17.2% 5/29 • Number of events 14 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Endocrine disorders Hypothyroidism	17.2% 5/29 • Number of events 5 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Infections and infestations Infections and infestations - Other, specify	17.2% 5/29 • Number of events 5 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Psychiatric disorders Insomnia	24.1% 7/29 • Number of events 7 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders - Other, specify	13.8% 4/29 • Number of events 5 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Gastrointestinal disorders Nausea	34.5% 10/29 • Number of events 13 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Neck pain	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Nervous system disorders Nervous system disorders - Other, specify	13.8% 4/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Eye disorders Night blindness	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
General disorders Non-cardiac chest pain	20.7% 6/29 • Number of events 6 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
General disorders Pain	37.9% 11/29 • Number of events 16 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Nervous system disorders Peripheral sensory neuropathy	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Postnasal drip	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Skin and subcutaneous tissue disorders Rash maculo-papular	13.8% 4/29 • Number of events 5 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Cardiac disorders Sinus tachycardia	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Surgical and medical procedures Surgical and medical procedures - Other, specify	13.8% 4/29 • Number of events 4 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Vascular disorders Thromboembolic event	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Nervous system disorders Tremor	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Infections and infestations Upper respiratory infection	10.3% 3/29 • Number of events 3 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Infections and infestations Urinary tract infection	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Ear and labyrinth disorders Vertigo	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Gastrointestinal disorders Vomiting	10.3% 3/29 • Number of events 5 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Investigations Weight loss	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Wheezing	6.9% 2/29 • Number of events 2 • From baseline until 28 days after the last dose of the study drug was received (±7 days). Treatment is continued until: > Disease progression. > Intercurrent illness that prevents further administration of treatment, > Unacceptable adverse event(s), > Participant decides to withdraw from the study, or > General or specific changes in the participant's condition render the participant unacceptable for further treatment in the opinion of the treating investigator Serious adverse events are defined as grade 3 or higher adverse events deemed to at least possibly related to the study drug.

Additional Information

Lecia Van Dam Sequist, M.D.

Massachusetts General Hospital

Phone: 617-724-4000

Email: lvsequist@partners.org

Results disclosure agreements

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