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).
Brief Title
Phase 2 Study of Poziotinib in Participants With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation
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 EGFR or 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.
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 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
NSCLC
Eligibility 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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
EGFR
HER2
Exon 20 insertion mutation
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03318939
Org Class
Industry
Org Full Name
Spectrum Pharmaceuticals, Inc
Org Study Id
SPI-POZ-202
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Study of Poziotinib in Patients With Non-Small Cell Lung Cancer (NSCLC), Locally Advanced or Metastatic, With EGFR or HER2 Exon 20 Insertion Mutation (ZENITH20)
Primary Outcomes
Outcome Description
The proportion of subjects who achieve Complete Response (CR) and Partial Response (PR) by the best response from the first dose of poziotinib to the end of study.
Outcome Measure
Objective Response Rate (ORR)
Outcome Time Frame
24 months
Secondary Outcomes
Outcome Description
The proportion of subjects who achieve CR, PR, and Stable Disease (SD) by the best response from the first dose of poziotinib to the end of study.
Outcome Time Frame
24 months
Outcome Measure
Disease Control Rate (DCR)
Outcome Description
Number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented.
Outcome Time Frame
24 months
Outcome Measure
Duration of Response (DoR)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404