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)
This study is for an investigational study drug called poziotinib for the treatment for EGFR or HER2 Exon 20 Insertion Mutation-Positive Non-Small Cell Lung Cancer. Poziotinib is a new type of treatment and is considered investigational. "Investigational" means that it has not yet been approved by the U.S. Food and Drug Administration (FDA) because we do not know enough about the benefits or side effects of poziotinib in the treatment for EGFR or HER2 Exon 20 Insertion Mutation-Positive Non-Small Cell Lung Cancer.
-To evaluate the Objective Response Rate (ORR) to poziotinib in patients with non-small cell lung cancer (NSCLC) with EGFR or HER2 (ErBB2) exon 20 insertion mutations.
- To evaluate other efficacy variables of poziotinib in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations, including the following:
-Disease Control Rate (DCR) (complete response + partial response + stable disease).
-Duration of Response (DoR).
-To evaluate the safety and tolerability of poziotinib in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations.
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 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: Participants 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
Tissue and plasma samples for mutation confirmation per protocol
Participant has adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling for retrospective central laboratory confirmation of mutation. If tissue is not available, patient must have biopsy accessible disease and must be willing to undergo a biopsy to provide an appropriate tissue sample prior to receiving treatment in the study.
Adequate organ function at Baseline.
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and a life expectancy of more than 6 months.
Females of childbearing potential must have a negative pregnancy test within 30 days prior to enrollment.
Participant is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 30 days after the last dose of poziotinib.
Cohort 7: EGFT Exon 19 deletion and L858R or HER2 T7981 mutations, EGFR and HER2 Exon 20 insertion mutation
Has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TK) prior to study participation.
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
Has a high risk of cardiac disease, as determined by the Investigator.
A history of other malignancies within the last 5 years, except for non-melanoma skin cancer or carcinoma in situ of the cervix.
Pregnant or breast-feeding.
Confirmed clinically significant or recent acute gastrointestinal disease.
Active Grade ≥2 skin disorder, rash, mucositis, or skin infection that needs medication or therapy or existing Grade ≥2 skin toxicity from previous therapies; Grade ≥2 neuropathy, Grade ≥2 pneumonitis.
unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (eg, Crohn¿s disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
Active liver disease or biliary tract disease (some exceptions apply).
Has an active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the patient to receive protocol treatment.
Participant has unstable, uncontrolled, active bleeding disorders, uses warfarin or other Coumadin-derived anticoagulants, has abnormal International Normalized Ratio (INR), or abnormal prothrombin time test within one month prior to that the study.
Cohort 5 only: Participant is eligible for treatment in an open Cohort (Cohorts 1-4)
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