NSCLC
Conditions
Keywords
EGFR, HER2, Exon 20 insertion mutation
Brief summary
This is a Phase 2, open-label, multi-center study to evaluate the efficacy and the safety/tolerability of poziotinib in seven participant cohorts for up to 603 previously treated and treatment-naïve NSCLC participant. Cohorts 3 and 4 were added with Amendment 1 and three additional cohorts were added with Amendment 2 (Cohorts 5, 6 and 7).
Detailed description
The Screening period (Day -30 to Day -1) lasts up to approximately 30 days prior to Cycle 1, Day 1. Participant must meet all Inclusion/Exclusion Criteria to participate in the study. Eligible participants will provide written Informed Consent prior to undergoing any study procedures. Each treatment cycle is 28 calendar days in duration. There will be seven participant cohorts and eligible participants will be enrolled into each cohort in parallel based on epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) exon 20 mutation status and prior treatment status: * Cohort 1: Previously treated participant with EGFR exon 20 insertion mutation positive NSCLC (complete) * Cohort 2: Previously treated participant with HER2 exon 20 insertion mutation positive NSCLC (complete) * Cohort 3: Treatment naïve participant with EGFR exon 20 insertion mutation positive NSCLC (complete) * Cohort 4: Treatment naïve participant with HER2 exon 20 insertion mutation positive NSCLC (fully enrolled) * Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed (closed to enrollment) * Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib (closed to enrollment) * Cohort 7: Participants with EGFR or HER2 activating mutations (closed to enrollment) Toxicity will be assessed based on the grade of the adverse events using CTCAE version 4.03. On Day 1 of each 28-day cycle, the participant's absolute neutrophil count (ANC) must be ≥1.5×10\^9/L and platelet count must be ≥100×10\^9/L before administering poziotinib. All participants will be treated until disease progression (except for first progression in Cohort 5), death, intolerable adverse events (AEs), or other protocol-specified reasons for participant withdrawal.
Interventions
DRUGPoziotinib
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Sponsors
Spectrum Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Each treatment cycle is 28 calendar days in duration. There will be seven participant cohorts and eligible participants will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20 mutation status and prior treatment status: * Cohort 1: Previously treated participants with EGFR exon 20 insertion mutant positive NSCLC (closed to enrollment) * Cohort 2: Previously treated participants with HER2 exon 20 insertion mutant positive NSCLC (closed to enrollment) * Cohort 3: Treatment naïve participants with EGFR exon 20 insertion mutant positive NSCLC (fully enrolled) * Cohort 4: Treatment naïve participants with HER2 exon 20 insertion mutant positive NSCLC * Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed * Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib * Cohort 7: Participants with EGFR or HER2 activating mutations
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participant must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements * Participant has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent * Prior treatment status: * Cohorts 1 and 2: Participant has had at least one prior systemic treatment for locally advanced or metastatic NSCLC * Cohorts 3 and 4: Participant is treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with poziotinib as determined by the Investigator. Adjuvant/neo-adjuvant therapies (chemotherapy, radiotherapy, or investigational agents) are permissible as long as they end at least 15 days prior to study entry. * Cohort 5: Participants who meet the criteria for enrollment in Cohorts 1 to 4, but the enrollment in the respective cohort has been closed * Cohort 6: Participant with EGFR mutation-positive NSCLC who progressed while on treatment with first-line osimertinib * Cohort 7: Participant has had at least one prior systemic treatment for locally advanced or metastatic NSCLC * Specific mutations: * Cohort 1 and 3: Documented EGFR exon 20 insertion mutation * Cohort 2 and 4: Documented HER2 exon 20 insertion mutation * Cohort 5: Documented EGFR or HER2 exon 20 insertion mutations * Cohort 6: Documented acquired EGFR mutation (tested after osimertinib progression) * Cohort 7: Documented EGFR or HER2 activating mutations * Participant has adequate organ function at Baseline Key
Exclusion criteria
* Participant has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible (Cohorts 1 and 2). * Participant is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks or 5 half lives, whichever is longer; local radiation therapy for bone pain may be allowed * Participant has had other malignancies within the past 3 years, except for stable non-melanoma skin cancer, fully-treated and stable, early-stage prostate cancer, or carcinoma in situ of the cervix or breast without need of treatment * Participant is pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 3 years | ORR was defined as the percentage of participants whose best overall response (BOR) was confirmed to be complete response (CR) or partial response (PR) from the first dose of poziotinib until the last tumor assessment on study. ORR was assessed by the Independent Radiologic Review Committee according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all non-nodal target lesions. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to 5 years | An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that occur from the first dose of study treatment until 35 (±5) days after the last dose of study treatment. |
| Disease Control Rate (DCR) | Up to 3 years | DCR was defined as percentage of participants with best response of CR, PR, or stable disease (SD) from the first dose of poziotinib to the last tumor assessment on study. CR was defined as the disappearance of all non-nodal target lesion. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present. SD was defined as neither sufficient shrinkage of target lesions to qualify for PR nor sufficient increase to qualify for progressive disease (PD). |
| Duration of Response (DoR) | Up to 3 years | DoR was evaluated only for participants who had CR or PR and was defined as the time 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. CR was defined as the disappearance of all non-nodal target lesion. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present. Disease progression was defined as greater than or equal to (≥) 20% increase in the SOD of target lesions taking as reference the nadir SOD (or the baseline, if the baseline is the nadir value). In addition to the relative increase of 20% in SOD, the SOD must also have demonstrated an absolute increase of ≥ 5 mm. |
Countries
Belgium, Canada, France, Israel, Italy, Netherlands, Spain, United States
Participant flow
Recruitment details
Participants were enrolled at 62 investigative sites from 11 October 2017 to 03 April 2023.
Pre-assignment details
A total of 648 participants were enrolled and dosed with Poziotinib.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 5.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants |
| Race/Ethnicity, Customized Black or African American | 46 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White | 481 Participants |
| Sex: Female, Male Female | 77 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 16 / 115 | 16 / 90 | 14 / 80 | 6 / 33 | 8 / 47 | 11 / 38 | 24 / 125 | 7 / 35 | 14 / 25 | 4 / 26 | 1 / 7 | 0 / 1 | 6 / 17 | 5 / 9 |
| other Total, other adverse events | 115 / 115 | 90 / 90 | 80 / 80 | 33 / 33 | 47 / 47 | 37 / 38 | 124 / 125 | 35 / 35 | 25 / 25 | 26 / 26 | 6 / 7 | 1 / 1 | 17 / 17 | 9 / 9 |
| serious Total, serious adverse events | 50 / 115 | 36 / 90 | 35 / 80 | 12 / 33 | 18 / 47 | 13 / 38 | 38 / 125 | 10 / 35 | 14 / 25 | 12 / 26 | 1 / 7 | 0 / 1 | 9 / 17 | 3 / 9 |
Outcome results
None listed