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

Spectrum Pharmaceuticals

Status and phase: Suspended; Phase 3

Conditions: NSCLC

Treatments: Drug: Poziotinib; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05378763

SPI-POZ-301

Details and patient eligibility

About

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.

Full 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.

Enrollment: 268 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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268 participants in 2 patient groups

Poziotinib 8 mg

Experimental group

Description:

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.

Treatment:

Drug: Poziotinib

Docetaxel 75 mg/m^2

Active Comparator group

Description:

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.

Treatment:

Drug: Docetaxel