Trial Outcomes & Findings for A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04) (NCT NCT02187744)

Last Updated: 2019-01-08

Results Overview

The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

226 participants

Primary outcome timeframe

Cycle 5

Results posted on

2019-01-08

Participant Flow

A single participant was randomized but not treated; this participant was included in the ITT population, but not in the Participant Flow, Per Protocol, or Safety populations.

Participant milestones

Participant milestones
Measure	PF-05280014 Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin area under the concentration versus time curve (AUC) 6 were administered on Day 1 of each cycle.	Trastuzumab-EU Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Study STARTED	113	112
Study COMPLETED	109	106
Study NOT COMPLETED	4	6
Treatment STARTED	113	112
Treatment COMPLETED	109	107
Treatment NOT COMPLETED	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-05280014 Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin area under the concentration versus time curve (AUC) 6 were administered on Day 1 of each cycle.	Trastuzumab-EU Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Study Participant refused further follow-up	1	0
Study Other	2	1
Study Lost to Follow-up	0	2
Study Related adverse event, not serious	0	2
Study Death	1	0
Study Related adverse event, serious non-fatal	0	1
Treatment Death	1	0
Treatment Related adverse event, serious non-fatal	0	1
Treatment Related adverse event, not serious	0	2
Treatment Lost to Follow-up	0	1
Treatment Other	2	0
Treatment Participant refused continued treatment	1	1

Baseline Characteristics

A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-05280014 n=114 Participants Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=112 Participants Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Total n=226 Participants Total of all reporting groups
Age, Continuous	54.0 Years STANDARD_DEVIATION 11.9 • n=5 Participants	51.2 Years STANDARD_DEVIATION 12.7 • n=7 Participants	52.6 Years STANDARD_DEVIATION 12.3 • n=5 Participants
Sex/Gender, Customized Female	114 Participants n=5 Participants	112 Participants n=7 Participants	226 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 5

Population: All participants who were HER2+ and randomized into the study; and who had received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Outcome measures

Outcome measures
Measure	PF-05280014 n=101 Participants Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=89 Participants Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.	92.1 Percentage of participants Interval 85.0 to 96.5	93.3 Percentage of participants Interval 85.9 to 97.5

SECONDARY outcome

Timeframe: Cycles 1 through 6

Population: All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.

Outcome measures

Outcome measures
Measure	PF-05280014 n=101 Participants Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=89 Participants Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. Cycle 1/Day 1 0 hours N= 101, 88	2.313 μg/mL Standard Deviation 17.949	1.318 μg/mL Standard Deviation 12.366
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. Cycle 1/Day 1 1 hour N= 97, 80	160.4 μg/mL Standard Deviation 57.329	164.8 μg/mL Standard Deviation 47.033
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. Cycle 2/Day 21 0 hours N= 99, 88	24.29 μg/mL Standard Deviation 13.796	27.20 μg/mL Standard Deviation 10.650
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. Cycle 4/Day 63 0 hours N= 98, 89	33.43 μg/mL Standard Deviation 14.488	37.33 μg/mL Standard Deviation 15.629
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. Cycle 5/Day 84 0 hours N= 101, 87	35.01 μg/mL Standard Deviation 15.571	40.44 μg/mL Standard Deviation 26.765
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. Cycle 5/Day 84 1 hour N= 90, 80	137.0 μg/mL Standard Deviation 37.748	138.8 μg/mL Standard Deviation 37.417
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. Cycle 6/Day 105 0 hours N= 101, 89	37.77 μg/mL Standard Deviation 17.523	40.10 μg/mL Standard Deviation 16.670

SECONDARY outcome

Timeframe: Cycle 6/End of treatment

Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.

Outcome measures

Outcome measures
Measure	PF-05280014 n=100 Participants Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=86 Participants Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.	47.0 Percentage of participants Interval 36.9 to 57.2	50.0 Percentage of participants Interval 39.0 to 61.0

SECONDARY outcome

Timeframe: Cycle 6/End of treatment

ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.

Outcome measures

Outcome measures
Measure	PF-05280014 n=101 Participants Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=89 Participants Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.	88.1 Percentage of participants Interval 80.2 to 93.7	82.0 Percentage of participants Interval 72.5 to 89.4

SECONDARY outcome

Timeframe: Cycles 1 through 6

Population: All participants who received at least 1 dose of study drug.

The number of participants with positive (titer \>=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.

Outcome measures

Outcome measures
Measure	PF-05280014 n=113 Participants Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=112 Participants Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6. Cycle 1 (n=113,112)	0 Number of participants	1 Number of participants
Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6. Cycle 2 (n=111,112)	0 Number of participants	0 Number of participants
Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6. Cycle 4 (n=108,109)	0 Number of participants	0 Number of participants
Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6. Cycle 6 (n=108,108)	0 Number of participants	0 Number of participants

SECONDARY outcome

Timeframe: Cycles 1 through 6

Population: All participants who received at least 1 dose of study drug.

The number of participants with positive (NAb response \>=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.

Outcome measures

Outcome measures
Measure	PF-05280014 n=113 Participants Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=112 Participants Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6. Cycle 4 (n=108,110)	0 Number of participants	0 Number of participants
Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6. Cycle 1 (n=113,112)	0 Number of participants	0 Number of participants
Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6. Cycle 2 (n=110,112)	0 Number of participants	0 Number of participants
Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6. Cycle 6 (n=108,108)	0 Number of participants	0 Number of participants

Adverse Events

PF-05280014

Serious events: 7 serious events

Other events: 106 other events

Deaths: 0 deaths

Trastuzumab-EU

Serious events: 6 serious events

Other events: 106 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PF-05280014 n=113 participants at risk Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=112 participants at risk Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Blood and lymphatic system disorders Febrile neutropenia	0.88% 1/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	1.8% 2/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Blood and lymphatic system disorders Neutropenia	0.88% 1/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.89% 1/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Blood and lymphatic system disorders Anaemia	0.00% 0/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.89% 1/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Blood and lymphatic system disorders Pancytopenia	0.88% 1/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.00% 0/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Gastrointestinal disorders Proctitis	0.88% 1/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.00% 0/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Infections and infestations Device related sepsis	0.88% 1/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.00% 0/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Infections and infestations Gastrointestinal infection	0.00% 0/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.89% 1/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Infections and infestations Injection site abscess	0.88% 1/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.00% 0/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Infections and infestations Tooth infection	0.00% 0/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.89% 1/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.89% 1/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Investigations Blood creatinine increased	0.88% 1/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.00% 0/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Metabolism and nutrition disorders Dehydration	0.00% 0/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.89% 1/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	0.89% 1/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.

Other adverse events

Additional Information

Pfizer CT.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	PF-05280014 n=113 participants at risk Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.	Trastuzumab-EU n=112 participants at risk Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Blood and lymphatic system disorders Anaemia	49.6% 56/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	45.5% 51/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Blood and lymphatic system disorders Neutropenia	32.7% 37/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	36.6% 41/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Blood and lymphatic system disorders Leukopenia	14.2% 16/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	22.3% 25/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Blood and lymphatic system disorders Thrombocytopenia	14.2% 16/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	17.0% 19/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Blood and lymphatic system disorders Febrile neutropenia	2.7% 3/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	5.4% 6/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Gastrointestinal disorders Nausea	33.6% 38/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	30.4% 34/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Gastrointestinal disorders Diarrhoea	14.2% 16/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	17.0% 19/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Gastrointestinal disorders Vomiting	6.2% 7/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	8.9% 10/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
General disorders Asthenia	31.9% 36/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	20.5% 23/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
General disorders Fatigue	13.3% 15/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	17.0% 19/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
General disorders Pyrexia	5.3% 6/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	4.5% 5/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Investigations Alanine aminotransferase increased	6.2% 7/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	8.9% 10/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Investigations Aspartate aminotransferase increased	2.7% 3/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	6.2% 7/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Metabolism and nutrition disorders Decreased appetite	11.5% 13/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	8.0% 9/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Musculoskeletal and connective tissue disorders Arthralgia	14.2% 16/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	7.1% 8/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Musculoskeletal and connective tissue disorders Bone pain	11.5% 13/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	4.5% 5/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Nervous system disorders Peripheral sensory neuropathy	6.2% 7/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	3.6% 4/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Nervous system disorders Dysgeusia	3.5% 4/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	5.4% 6/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Nervous system disorders Neuropathy peripheral	5.3% 6/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	3.6% 4/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
Skin and subcutaneous tissue disorders Alopecia	63.7% 72/113 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.	61.6% 69/112 • Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose. Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.