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

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)

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.

Study Overview

• Status: Suspended
• Conditions: NSCLC
• Intervention / Treatment: Drug: Poziotinib; Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 268
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Winter Haven, Florida, United States, 33880
      • Bond Clinic, P.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participant must:

1. Be willing and capable of providing signed and dated Informed Consent, adhering to dosing and visit schedules, and meeting the study requirements
2. Have histologically or cytologically confirmed NSCLC
3. Have at least one measurable NSCLC target lesion per RECIST v.1.1 by local assessment
4. 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.
5. Have documentation of HER2 exon 20 mutation
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
7. Have adequate hematologic, hepatic, and renal function at Baseline as per protocol

Exclusion Criteria:

Participant:

1. Has had previous treatment with poziotinib for treatment of NSCLC
2. Has EGFR or anaplastic lymphoma kinase (ALK) genome tumor alterations
3. 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
4. Has spinal cord compression or leptomeningeal disease
5. Has a high risk of cardiac disease, as determined by the Investigator
6. Has a history of, or signs of Grade ≥2 pneumonitis on current imaging studies
7. Is unable to take drugs orally
8. Is pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Poziotinib 8 mg; 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; Poziotinib tablets; Other Names: HM781-36
Active Comparator: Docetaxel 75 mg/m^2; 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; Docetaxel IV infusion

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

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Estimated): December 25, 2027
• Study Completion (Estimated): December 25, 2028

Study Registration Dates

• First Submitted: May 9, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: HER2; Epidermal growth factor receptor (EGFR); Exon 20 mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: SPI-POZ-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No