Trial Outcomes & Findings for A Study Of The Safety And Tolerability Of HKI-272 Administered Orally To Japanese Subjects With Advanced Solid Tumors (NCT NCT00397046)

Last Updated: 2018-09-14

Results Overview

DLT was defined as any drug-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, except the grade 3 nausea, vomiting, diarrhea, or rash, unless the subject was receiving appropriate medical therapy. Additional DLTs included the following: grade 2 or 3 diarrhea lasting 2 or more days for which the subject was receiving medical therapy or that was associated with fever or dehydration.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

21 participants

Primary outcome timeframe

First dose date through 21 days

Results posted on

2018-09-14

Participant Flow

Participant milestones

Participant milestones
Measure	Neratinib 80 mg Neratinib 80 mg qd	Neratinib 160 mg Neratinib 160 mg qd	Neratinib 240 mg Neratinib 240 mg qd	Neratinib 320 mg Neratinib 320 mg qd
Overall Study STARTED	3	3	10	5
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	3	3	10	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Neratinib 80 mg Neratinib 80 mg qd	Neratinib 160 mg Neratinib 160 mg qd	Neratinib 240 mg Neratinib 240 mg qd	Neratinib 320 mg Neratinib 320 mg qd
Overall Study Disease Progression	3	3	10	5

Baseline Characteristics

A Study Of The Safety And Tolerability Of HKI-272 Administered Orally To Japanese Subjects With Advanced Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Neratinib 80 mg n=3 Participants Neratinib 80 mg qd	Neratinib 160 mg n=3 Participants Neratinib 160 mg qd	Neratinib 240 mg n=10 Participants Neratinib 240 mg qd	Neratinib 320 mg n=5 Participants Neratinib 320 mg qd	Total n=21 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	14 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	7 Participants n=21 Participants
Age, Continuous	53.67 years STANDARD_DEVIATION 9.50 • n=5 Participants	48.33 years STANDARD_DEVIATION 5.13 • n=7 Participants	62.50 years STANDARD_DEVIATION 10.19 • n=5 Participants	59.40 years STANDARD_DEVIATION 7.64 • n=4 Participants	58.48 years STANDARD_DEVIATION 9.86 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Race/Ethnicity, Customized Japanese	3 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants	5 Participants n=4 Participants	21 Participants n=21 Participants

PRIMARY outcome

Timeframe: First dose date through 21 days

Population: All subjects who received at least one dose.

Outcome measures

Outcome measures
Measure	Neratinib 80 mg n=3 Participants Neratinib 80 mg qd	Neratinib 160 mg n=3 Participants Neratinib 160 mg qd	Neratinib 240 mg n=10 Participants Neratinib 240 mg qd	Neratinib 320 mg n=5 Participants Neratinib 320 mg qd
Dose Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: First dose date through 21 days

Population: All subjects who received at least one dose.

MTD is defined as the prior dose level of the dose level which has \>=2 of 3 to 6 subjects that experience a neratinib-related DLT during 21 days from first dose date. A DLT is defined as any HKI-272-related nonhematologic grade 3 or any grade 4 AE according to the Common Terminology Criteria for Adverse Events version 3.0 except: Grade 3 nausea, vomiting, diarrhea, or rash unless subject was receiving appropriate medical therapy.

Outcome measures

Outcome measures
Measure	Neratinib 80 mg n=21 Participants Neratinib 80 mg qd	Neratinib 160 mg Neratinib 160 mg qd	Neratinib 240 mg Neratinib 240 mg qd	Neratinib 320 mg Neratinib 320 mg qd
Maximum Tolerated Dose (MTD)	240 mg	—	—	—

SECONDARY outcome

Timeframe: From first dose date to disease progression or last tumor assessment, up to 9.2 months

Population: Subjects who received at least 14 days of continual dose administration of drug and who had undergone at least 1 follow-up tumor assessment were considered evaluable for efficacy

ORR is defined as the proportion of subjects who had either a complete response (CR) or partial response (PR), according to a modified Response Evaluation Criteria in Solid Tumors (RECIST). The modified RECIST is defined as CR: Disappearance of all target lesions, PR: At least a 30% decrease in the sum of the Longest Diameters (LDs) of target lesions, taking as reference the baseline sum LDs. Response required confirmation.

Outcome measures

Outcome measures
Measure	Neratinib 80 mg n=3 Participants Neratinib 80 mg qd	Neratinib 160 mg n=3 Participants Neratinib 160 mg qd	Neratinib 240 mg n=10 Participants Neratinib 240 mg qd	Neratinib 320 mg n=5 Participants Neratinib 320 mg qd
Objective Response Rate (ORR)	0 percentage of participants Exact Confidence Interval not computed for ORR=0%	0 percentage of participants Exact Confidence Interval not computed for ORR=0%	10.0 percentage of participants Interval 0.3 to 44.5	20.0 percentage of participants Interval 0.5 to 71.6

SECONDARY outcome

Timeframe: From first dose date to progression/death or last assessment, up to 9.2 months.

Population: Subjects who received at least 14 days of continual dose administration of drug and who had undergone at least 1 follow-up tumor assessment were considered evaluable for efficacy

Subjects with confirmed Complete Response (CR) or confirmed Partial Response (PR), or Stable Disease (SD) \>= 24 weeks, according to a modified Response Evaluation Criteria in Solid Tumors (RECIST). SD is defined as SD in target lesions and a non-progressive disease (PD) in nontarget lesions; A PR is defined as either a PR in target lesions and a non-PD in nontarget lesions, or a CR in target lesions and an incomplete response or SD in nontarget lesions; and a CR is defined as a CR in target lesions and a CR in nontarget lesions.

Outcome measures

Outcome measures
Measure	Neratinib 80 mg n=3 Participants Neratinib 80 mg qd	Neratinib 160 mg n=3 Participants Neratinib 160 mg qd	Neratinib 240 mg n=10 Participants Neratinib 240 mg qd	Neratinib 320 mg n=5 Participants Neratinib 320 mg qd
Clinical Benefit Rate	0 percentage of participants Exact Confidence Interval not computed for ORR=0%	0 percentage of participants Exact Confidence Interval not computed for ORR=0%	30.0 percentage of participants Interval 6.7 to 65.2	40.0 percentage of participants Interval 5.3 to 85.3

Adverse Events

Neratinib 80 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Neratinib 160 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Neratinib 240 mg

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Neratinib 320 mg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Neratinib 80 mg n=3 participants at risk Neratinib 80 mg qd	Neratinib 160 mg n=3 participants at risk Neratinib 160 mg qd	Neratinib 240 mg n=10 participants at risk Neratinib 240 mg qd	Neratinib 320 mg n=5 participants at risk Neratinib 320 mg qd
Gastrointestinal disorders Dysphagia	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	10.0% 1/10 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/5 • From first dose to 28 days after last dose, up to 9.2 months.
Gastrointestinal disorders Nausea	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/10 • From first dose to 28 days after last dose, up to 9.2 months.	20.0% 1/5 • From first dose to 28 days after last dose, up to 9.2 months.
Gastrointestinal disorders Varices oesophageal	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	10.0% 1/10 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/5 • From first dose to 28 days after last dose, up to 9.2 months.
General disorders Fatigue	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	20.0% 2/10 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/5 • From first dose to 28 days after last dose, up to 9.2 months.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	10.0% 1/10 • From first dose to 28 days after last dose, up to 9.2 months.	20.0% 1/5 • From first dose to 28 days after last dose, up to 9.2 months.
Renal and urinary disorders Hydronephrosis	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/10 • From first dose to 28 days after last dose, up to 9.2 months.	20.0% 1/5 • From first dose to 28 days after last dose, up to 9.2 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/3 • From first dose to 28 days after last dose, up to 9.2 months.	10.0% 1/10 • From first dose to 28 days after last dose, up to 9.2 months.	0.00% 0/5 • From first dose to 28 days after last dose, up to 9.2 months.

Other adverse events

Additional Information

Senior Director, Clinical Operations

Puma Biotechnology, Inc.

Phone: +1 (424) 248-6500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60