Trial Outcomes & Findings for A Study of Poziotinib in Patients With Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Activating Mutations in Advanced Malignancies (NCT NCT04172597)

Last Updated: 2024-03-13

Results Overview

ORR was defined as the percentage of participants with confirmed complete response (CR) and partial response (PR) as assessed by the investigator using local radiology evaluation according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

1 participants

Primary outcome timeframe

Up to 168 days

Results posted on

2024-03-13

Participant Flow

The participant was enrolled at 1 site in the United States.

Participant milestones

Participant milestones
Measure	Cohort 1 Participants with human epidermal growth factor receptor 2 (HER2) positive or HER2-negative breast cancer (BC) with a HER2 activating mutation were to receive poziotinib 8 milligrams (mg), orally, twice daily (BID) starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable adverse events (AEs), or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.	Cohort 2 Participants with colorectal cancer (CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 3 Participants with solid tumors (except non-small cell lung cancer (NSCLC), BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 4 Participants with glioblastoma (GBM) with epidermal growth factor receptor (EGFR) activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 5 Participants with solid tumors (except NSCLC or GBM) with EGFR activating mutations were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.
Overall Study STARTED	0	0	0	0	1
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Participants with human epidermal growth factor receptor 2 (HER2) positive or HER2-negative breast cancer (BC) with a HER2 activating mutation were to receive poziotinib 8 milligrams (mg), orally, twice daily (BID) starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable adverse events (AEs), or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.	Cohort 2 Participants with colorectal cancer (CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 3 Participants with solid tumors (except non-small cell lung cancer (NSCLC), BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 4 Participants with glioblastoma (GBM) with epidermal growth factor receptor (EGFR) activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 5 Participants with solid tumors (except NSCLC or GBM) with EGFR activating mutations were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.
Overall Study Disease Progression	0	0	0	0	1

Baseline Characteristics

The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 Participants with HER2-positive or HER2-negative BC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to the treating physician's instructions.	Cohort 2 Participants with CRC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 3 Participants with solid tumors (except NSCLC, BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 4 Participants with GBM with EGFR activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 5 n=1 Participants Participants with solid tumors (except NSCLC or GBM) with EGFR activating mutations were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Total n=1 Participants Total of all reporting groups
Sex: Female, Male Female	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Sex: Female, Male Male	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Ethnicity (NIH/OMB) Hispanic or Latino	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Ethnicity (NIH/OMB) Not Hispanic or Latino	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Ethnicity (NIH/OMB) Unknown or Not Reported	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Race (NIH/OMB) American Indian or Alaska Native	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Race (NIH/OMB) Asian	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Race (NIH/OMB) Black or African American	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Race (NIH/OMB) White	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Race (NIH/OMB) More than one race	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.
Race (NIH/OMB) Unknown or Not Reported	—	—	—	—	—	0 Participants The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.

PRIMARY outcome

Timeframe: Up to 168 days

Population: The Evaluable Population included all enrolled participants who completed at least 6 weeks of poziotinib treatment, had baseline and at least 1 post-baseline tumor response evaluation using RECIST, v1.1, or progressed prior to any post-baseline image evaluation. As the study was terminated early by the sponsor, there were no participants enrolled in cohorts 1-4.

Outcome measures

Outcome measures
Measure	Cohort 1 Participants with HER2 positive or HER2-negative BC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.	Cohort 2 Participants with CRC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 3 Participants with solid tumors (except NSCLC, BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions	Cohort 4 Participants with GBM with EGFR activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions	Cohort 5 n=1 Participants Participants with solid tumors (except NSCLC or GBM) with EGFR activating mutations were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.
Objective Response Rate (ORR)	—	—	—	—	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 168 days

Population: The Evaluable Population included all enrolled participants who completed at least 6 weeks of poziotinib treatment, had baseline and at least 1 post-baseline tumor response evaluation using RECIST, v1.1 or progressed prior to any post-baseline image evaluation. As the study was terminated early by the sponsor, there were no participants enrolled in cohorts 1-4.

Duration of response was defined as the time from the date that measurement criteria are first met for CR or PR until the first subsequent date that progressive disease or death is documented. CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Disease progression (PD) is defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 168 days

Population: The Evaluable Population included all enrolled participants who completed at least 6 weeks of poziotinib treatment, had baseline and at least 1 post-baseline tumor response evaluation using RECIST, v1.1 or progressed prior to any post-baseline image evaluation. As the study was terminated early by the sponsor, there were no participants enrolled in cohorts 1-4.

DCR is defined as percentage of participants with best response of CR, PR, and stable disease (SD) from the first dose of poziotinib to the end of study. CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter (LD) since the treatment started.

Outcome measures

Outcome measures
Measure	Cohort 1 Participants with HER2 positive or HER2-negative BC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.	Cohort 2 Participants with CRC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.	Cohort 3 Participants with solid tumors (except NSCLC, BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions	Cohort 4 Participants with GBM with EGFR activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions	Cohort 5 n=1 Participants Participants with solid tumors (except NSCLC or GBM) with EGFR activating mutations were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.
Disease Control Rate (DCR)	—	—	—	—	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 30 days after last dose of study drug (Up to 199 days)

Population: The Safety Analysis Population included all enrolled patients who received at least 1 dose of poziotinib. As the study was terminated early by the sponsor, there were no participants enrolled in cohorts 1-4.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.