Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer

MTD reflects the highest dose of capecitabine in combination with neratinib that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.

Time frame: From first dose date to day 21.

Population: All patients in the safety population in part 1 (dose-escalation) of the study.

MTD reflects the highest dose of neratinib plus capeciteabine that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.

Time frame: From first dose date to day 21.

Population: All patients in the safety population in part 1 (dose-escalation) of the study.

Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).

Time frame: From first dose date to day 21

Population: Safety population

The percentage of subjects with Complete Response, Partial Response, or Stable Disease at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Time frame: From first dose date to progression or last tumor assessment, up to three years.

Population: Evaluable Population includes subjects who met all inclusion/exclusion criteria, received at least two weeks of neratinib and capecitabine, and underwent valid tumor assessments at baseline and at least one post-baseline time point stratified by prior Lapatinib exposure.

Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date of recurrence or progressive disease (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

Time frame: From start date of response to first PD/death, up to three years.

Population: Evaluable Population includes subjects who met all inclusion/exclusion criteria, received at least two weeks of neratinib and capecitabine, and underwent valid tumor assessments at baseline and at least one post-baseline time point stratified by prior Lapatinib exposure.

Number of Subjects with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

Time frame: From first dose date to progression or last tumor assessment, up to three years.

Population: Evaluable Population includes subjects who met all inclusion/exclusion criteria, received at least two weeks of neratinib and capecitabine, and underwent valid tumor assessments at baseline and at least one post-baseline time point stratified by prior Lapatinib exposure.