A Study of Poziotinib in Previously Treated Participants With Locally Advanced or Metastatic NSCLC Harboring HER2 Exon 20 Mutations

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to compare the progression-free survival (PFS) in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) exon 20 mutations when treated with poziotinib versus docetaxel.

Detailed Description
-----------------
This is a Phase 3, active-controlled, multicenter study to compare the efficacy and safety/tolerability of poziotinib versus docetaxel in previously treated participants with locally advanced or metastatic NSCLC harboring HER2 exon 20 mutations. Participants will be randomized in a 2:1 ratio to: Arm A: Poziotinib 8 milligrams (mg), twice daily (BID) or Arm B: Docetaxel 75 milligrams per meter square (mg/m^2) The Screening Period lasts up to 21 days prior to Cycle 1, Day 1 (C1D1). Participants will be treated in 21-day cycles or until disease progression, death, intolerable adverse events (AEs), initiation of non-protocol anti-cancer treatment, or other protocol-specified reasons.

Official Title
-----------------
A Randomized, Phase 3 Study of Poziotinib in Previously Treated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring HER2 Exon 20 Mutations (PINNACLE)

Conditions
-----------------
NSCLC

Intervention / Treatment
-----------------
* Drug: Poziotinib
* Drug: Docetaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must: Be willing and capable of providing signed and dated Informed Consent, adhering to dosing and visit schedules, and meeting the study requirements Have histologically or cytologically confirmed NSCLC Have at least one measurable NSCLC target lesion per RECIST v.1.1 by local assessment Participant has had at least one prior systemic treatment for locally advanced or metastatic NSCLC, including platinum and a checkpoint inhibitor (CPI) therapy, unless the investigator affirms that a CPI was not medically indicated. Have documentation of HER2 exon 20 mutation Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 Have adequate hematologic, hepatic, and renal function at Baseline as per protocol Exclusion Criteria: Participant: Has had previous treatment with poziotinib for treatment of NSCLC Has EGFR or anaplastic lymphoma kinase (ALK) genome tumor alterations Has had previous treatment with docetaxel for locally advanced or metastatic NSCLC. If docetaxel was received in the neo-adjuvant or adjuvant setting, progressive disease must have occurred ≥6 months after the last dose to be eligible Has spinal cord compression or leptomeningeal disease Has a high risk of cardiac disease, as determined by the Investigator Has a history of, or signs of Grade ≥2 pneumonitis on current imaging studies Is unable to take drugs orally Is pregnant or breast-feeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Poziotinib 8 mg<br>Participants will receive poziotinib 8 mg, orally, BID, in 21 day cycles or until disease progression, death, intolerable adverse events (AEs), initiation of non-protocol anti-cancer treatment, or other protocol-specified reasons for participant withdrawal from the study. | Drug: Poziotinib<br>* Poziotinib tablets<br>* Other names: HM781-36;|
| Active Comparator: Docetaxel 75 mg/m^2<br>Participants will receive docetaxel 75 mg/m^2, intravenously (IV) on Day 1 of each 21-day treatment cycle or until disease progression, death, intolerable AEs, initiation of non-protocol anti-cancer treatment, or other protocol-specified reasons for participant withdrawal from the study. | Drug: Docetaxel<br>* Docetaxel IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time (in months) from the start of the study treatment to the date of first documented disease progression by central radiographic evaluation per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1) or death due to any cause, whichever occurs first. | Up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as the time (in months) from the start of study treatment to the date of death due to any cause. | Up to approximately 5 years | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of participants who achieve at least one complete response (CR) or partial response (PR) by the central radiographic evaluation as per the RECIST v.1.1 criteria, before disease progression. Per RECIST v.1.1 for solid tumors, CR is defined as disappearance of all tumor lesions (TLs) and disappearance or reduction of all pathological lymph nodes <10mm (short axis). PR is ≥30% decrease in sum of diameters (SOD) from Baseline. | Up to approximately 5 years | 
| Disease Control Rate (DCR) | DCR is defined as the proportion of participants who achieve at least one CR, PR, stable disease (SD), or non-CR/non-progressive disease (PD), by the central radiographic evaluation per the RECIST v.1.1 criteria, before disease progression. Per RECIST v.1.1 for solid tumors, CR is defined as disappearance of all tumor lesions (TLs) and disappearance or reduction of all pathological lymph nodes <10mm (short axis). PR is ≥30% decrease in sum of diameters (SOD) from Baseline, and non PD is ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm). SD is SOD change neither sufficient for PR nor sufficient for PD. | Up to approximately 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HER2, Epidermal growth factor receptor (EGFR), Exon 20 mutation