Study of Poziotinib in Participants With HER2-Positive Metastatic Breast Cancer

ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) among participants in the Evaluable Population assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR was based on investigator assessed BOR. Per RECIST v1.1 for target lesions, CR was disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis \<10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (PD) (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm).

Time frame: Up to 24 months

Population: Evaluable Population included all enrolled participants who completed at least 1 cycle of poziotinib treatment and had at least 1 post-baseline tumor response evaluation using RECIST, v 1.1.

DCR was the percentage of participants whose best response was CR, PR or stable disease (SD) among participants in the Evaluable Population assessed per RECIST v1.1. DCR was based on investigator-assessed BOR. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target TLs and all target LNs with short axis \<10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm). SD was SOD change neither sufficient for PR nor sufficient for PD.

Time frame: Up to 24 months

Population: Evaluable Population included all enrolled participants who completed at least 1 cycle of poziotinib treatment and had at least 1 post-baseline tumor response evaluation using RECIST, v 1.1.

DoR was evaluated only for participants whose BOR was CR or PR and was defined as the time (in months) from the date that response evaluation criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that PD or death was documented. DoR of participants without documented PD or death was censored at the time of last tumor assessment. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis \<10mm. PR was defined as ≥30% decrease in sum of diameters (SOD) from Baseline, and not PD. PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm).

Time frame: Up to 24 months

Population: Evaluable Population included all participants who had received at least one cycle of poziotinib and had at least one evaluable post-baseline tumor response evaluation using response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST, v1.1). Overall number of participants analyzed is the number of participants with best overall response of CR or PR.

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were AEs that occurred or worsened from the first dose of study treatment until 35 (± 5) days after the last dose of study treatment.

Time frame: From the first dose of study drug administration until 35 (± 5) days after the last dose of study drug administration (Up to approximately 25 months)

Population: Safety Population included all participants who received at least 1 dose of poziotinib.

Time frame: For Cohort 1: Pre-dose and 1 and 2 hours post-dose on Day 1 of Cycles 1, 2, and 3, and pre-dose on Day 14 of Cycle 1 For Cohort 2: Day 1 of Cycle 1 pre-dose and 30 minutes, 1,1.5,2,3, 4, 6, and 24 hours post-dose of Day 1 of Cycle 1

Population: Pharmacokinetic analyses specified in the protocol were not performed as the samples were no longer stable at the time of the analysis.

PFS was the duration of time (in months) from first administration of study treatment to date of first documented disease progression or death from any cause. PFS of living participants without documented PD was censored at the time of last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm.

Time frame: Up to 24 Months

Population: Evaluable Population included all enrolled participants who completed at least 1 cycle of poziotinib treatment and had at least 1 post-baseline tumor response evaluation using RECIST, v 1.1.

TTP was defined as the time (in months) from first administration of study drug to tumor progression, which excluded death without tumor progression, by the end of study. TTP of participants who died without documented PD was censored at date of death. TTP of living participants without documented PD was censored at the same time as PFS, which was the last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm.

Time frame: Up to 24 months

Population: Evaluable Population included all enrolled participants who completed at least 1 cycle of poziotinib treatment and had at least 1 post-baseline tumor response evaluation using RECIST, v 1.1.