Trial Outcomes & Findings for A Study of Docetaxel + ARN-509 in Castration-Resistant Prostate Cancer (NCT NCT03093272)

NCT ID: NCT03093272

Last Updated: 2020-04-09

Results Overview

Progression free survival (PFS) is defined as the time from treatment initiation until the occurrence of one of the following: 1. A participant was considered to have progressed by bone scan if 1. the first bone scan with greater than or equal to (≥) 2 new lesions compared to baseline was observed in less than (\<) 12 weeks from study drug initiation and was confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); 2. the first bone scan with ≥2 new lesions compared to baseline was observed in ≥12 weeks from study drug initiation and the new lesions were verified on the next bone scan ≥6 weeks later (a total of ≥2 new lesions compared to baseline); 2. Progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) by RECIST v. 1.1; or 3. Death from any cause.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: Disease was evaluated radiologically at baseline and every 12 weeks on treatment; PFS follow up was up to 9.4 months
• Results posted on: 2020-04-09

Participant Flow

Participant milestones

Measure	Apalutamide Combined With Docetaxel * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Docetaxel + ARN-509 in Castration-Resistant Prostate Cancer

Baseline characteristics by cohort

Measure	Apalutamide Combined With Docetaxel n=9 Participants * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Age, Customized <60	1 Participants n=5 Participants
Age, Customized 60-69	3 Participants n=5 Participants
Age, Customized 70-79	4 Participants n=5 Participants
Age, Customized 80-89	1 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · White	8 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic	1 Participants n=5 Participants
Region of Enrollment United States	9 Participants n=5 Participants
Prior treatment with abiraterone acetate	9 Participants n=5 Participants
Duration on abiraterone acetate	5.5 months n=5 Participants
Time interval between abiraterone acetate initiation and protocol treatment	6.0 months n=5 Participants
ECOG performance status Performance Status 0	7 Participants n=5 Participants
ECOG performance status Performance Status 1	2 Participants n=5 Participants
Gleason score Gleason Score 6	1 Participants n=5 Participants
Gleason score Gleason Score 7	0 Participants n=5 Participants
Gleason score Gleason Score 8-10	7 Participants n=5 Participants
Gleason score Gleason Score Missing	1 Participants n=5 Participants
PSA level	48.3 ng/mL n=5 Participants
Number of Patients with Disease in Specific Sites Bone	8 Participants n=5 Participants
Number of Patients with Disease in Specific Sites Lymph Nodes	6 Participants n=5 Participants
Number of Patients with Disease in Specific Sites Prostate	1 Participants n=5 Participants
Number of Patients with Disease in Specific Sites Liver	1 Participants n=5 Participants
Number of Patients with Disease in Specific Sites Others	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 12 weeks on treatment; PFS follow up was up to 9.4 months

Population: Three patients did not have the progression defined by protocol (patients 1, 2, and 8). Two patients (patients 2 and 8) did not have follow-up scans, and thus PFS was censored at the date of the registration. One patient (patient 1) progressed via rising PSA, not radiographically.

Progression free survival (PFS) is defined as the time from treatment initiation until the occurrence of one of the following:

1. A participant was considered to have progressed by bone scan if

1. the first bone scan with greater than or equal to (≥) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from study drug initiation and was confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline);

2. the first bone scan with ≥2 new lesions compared to baseline was observed in ≥12 weeks from study drug initiation and the new lesions were verified on the next bone scan ≥6 weeks later (a total of ≥2 new lesions compared to baseline);

2. Progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) by RECIST v. 1.1; or

3. Death from any cause.

Outcome measures

Measure	Apalutamide Combined With Docetaxel n=9 Participants * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 1	5.6 months
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 2	NA months Patient did not have follow up scans to document PFS.
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 3	5.6 months
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 4	8.1 months
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 5	1.8 months
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 6	4.8 months
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 7	5.1 months
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 8	NA months Patient did not have follow up scans to document PFS.
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide Participant 9	9.4 months

SECONDARY outcome

Timeframe: First 3 weeks of treatment

Population: If the first 3 patients were accrued had no DLTs, then an additional 3 patients were accrued to observe for DLTs. If less than 2 patients experienced a DLT, the study opened to full accrual.

Specific adverse events will be recorded during the safety lead-in phase of 6 patients. Any toxicities considered unacceptable during this time will be considered a dose-limiting toxicity and will be summarized among all patients evaluable for a dose-limiting toxicity (DLT).

Outcome measures

Measure	Apalutamide Combined With Docetaxel n=6 Participants * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Number of Participants With Dose-Limiting Toxicities in the Safety Lead-in Group (First 6 Patients) Dose-limiting toxicity identified	0 Participants
Number of Participants With Dose-Limiting Toxicities in the Safety Lead-in Group (First 6 Patients) No dose-limiting toxicity identified	6 Participants

SECONDARY outcome

Timeframe: Cycle 1, 2: During infusion at pre-dose, 15 minutes and 30 minutes post-dose, end of dose, and 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post dose.

Population: Pharmacokinetic samples were not collected or received for 3 patients during C2D1.

The pharmacokinetic (PK) parameters of the first 9 patients enrolled at Dana-Farber Cancer Institute will be determined using noncompartmental methods with WinNonLin version 5.2. Maximum blood concentration (Cmax) will be determined by visual inspection. Due to the premature termination of the study, only 9 patients were evaluated. The PK samples were collected on Days 1 and 2 of the first two treatment cycles.

Outcome measures

Measure	Apalutamide Combined With Docetaxel n=9 Participants * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Maximum Blood Concentration (Cmax) for Docetaxel Pharmacokinetic Analysis Cycle 1	2415 ng/mL Standard Deviation 970
Maximum Blood Concentration (Cmax) for Docetaxel Pharmacokinetic Analysis Cycle 2	1641 ng/mL Standard Deviation 867

SECONDARY outcome

Timeframe: Cycle 1, 2: During infusion at pre-dose, 15 minutes and 30 minutes post-dose, end of dose, and 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post dose.

Population: Pharmacokinetic samples were not collected or received for 3 patients during C2D1.

The area under the blood concentration-time curve (linear trapezoidal rule) will be determined between 0-24 hours (AUC0-24). The PK samples were collected during the first two days of cycles 1 and 2.

Outcome measures

Measure	Apalutamide Combined With Docetaxel n=9 Participants * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Area Under the Curve (AUC) for Docetaxel Pharmacokinetic Analysis Cycle 1	3406 ng•h/mL Standard Deviation 1426
Area Under the Curve (AUC) for Docetaxel Pharmacokinetic Analysis Cycle 2	3095 ng•h/mL Standard Deviation 1407

SECONDARY outcome

Timeframe: PSA was measured on Cycle 1 Day 1 (Baseline) and at 12 weeks on treatment.

The maximum percent PSA change (rise or fall) from baseline to after 12 weeks on study. For patients who discontinue on or before the 12 week assessment or for whom the 12 week assessment is missing, the last observation prior to the week 12 assessment will be utilized. Patients with no post-baseline PSA data will be excluded from the summary.

Outcome measures

Measure	Apalutamide Combined With Docetaxel n=9 Participants * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Serum PSA Change From Baseline to 12 Weeks on Treatment	13.0 percent Interval -36.3 to 28.8

SECONDARY outcome

Timeframe: Measured from end of study treatment to death due to any cause; OS measured as 22.4 months

Overall Survival (OS) is defined as the time from trial treatment start to death due to any cause, or censored at date last known alive.

Outcome measures

Measure	Apalutamide Combined With Docetaxel n=9 Participants * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Overall Survival Participant 1	22.4 months
Overall Survival Participant 2	4.2 months
Overall Survival Participant 3	21.2 months
Overall Survival Participant 4	16.8 months
Overall Survival Participant 5	1.8 months
Overall Survival Participant 6	9.0 months
Overall Survival Participant 7	10.1 months
Overall Survival Participant 8	5.9 months
Overall Survival Participant 9	12.2 months

Adverse Events

Apalutamide Combined With Docetaxel

Serious events: 4 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Measure	Apalutamide Combined With Docetaxel n=9 participants at risk * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
General disorders Infusion related reaction	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Investigations Neutrophil count decreased	22.2% 2/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Pneumonitis	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Respiratory failure	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use

Other adverse events

Measure	Apalutamide Combined With Docetaxel n=9 participants at risk * Apalutamide (ARN-509): 240mg (four 60mg tablets), oral, once daily * Docetaxel: 75mg/m2 in 250cc Normal Saline, IV, every 21 days (3 weeks) * Prednisone: 5mg, oral, twice daily
Endocrine disorders Hyperthyroidism	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Endocrine disorders Hypothyroidism	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Eye disorders Eye disorders - Other, specify - Blepharitis	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Gastrointestinal disorders Diarrhea	22.2% 2/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Gastrointestinal disorders Enterocolitis	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Gastrointestinal disorders Mucositis oral	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Gastrointestinal disorders Nausea	33.3% 3/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Gastrointestinal disorders Vomiting	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
General disorders Fatigue	44.4% 4/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
General disorders Fever	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
General disorders General disorders and administration site conditions - Other, specify - Infusion Related Reaction	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
General disorders General disorders and administration site conditions - Other, specify - Rhinorrhea	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
General disorders Infusion related reaction	33.3% 3/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Infections and infestations Paronychia	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Infections and infestations Urinary tract infection	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Investigations Alkaline phosphatase increased	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Investigations Aspartate aminotransferase increased	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Investigations Neutrophil count decreased	44.4% 4/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Investigations Urine output decreased	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Musculoskeletal and connective tissue disorders Bone pain	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Musculoskeletal and connective tissue disorders Myalgia	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Nervous system disorders Dysgeusia	22.2% 2/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Nervous system disorders Peripheral sensory neuropathy	22.2% 2/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Psychiatric disorders Insomnia	22.2% 2/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Renal and urinary disorders Urinary incontinence	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Cough	33.3% 3/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Pneumonitis	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Postnasal drip	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Respiratory, thoracic and mediastinal disorders Respiratory failure	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Skin and subcutaneous tissue disorders Alopecia	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Skin and subcutaneous tissue disorders Rash acneiform	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Skin and subcutaneous tissue disorders Rash maculo-papular	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify - Nail Changes	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify - Rash	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify - Rash - Unspecified	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify - Tearing	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use
Vascular disorders Hypertension	11.1% 1/9 • Participants were assessed for adverse events on days 1, 8 and 15 for cycle 1, on days 1 and 15 for cycle 2, and every cycle thereafter; Treatment duration was up to 12 cycles in this study (1 cycle=21 days). Maximum grade toxicity by type was first calculated. Serious adverse events were defined as any untoward medical occurrence based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use

Additional Information

Lauren Harshman, MD

Dana-Farber Cancer Institute

Phone: 617-632-2429

Email: laurenc_harshman@dfci.harvard.edu

Results disclosure agreements

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