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

Phase 3

Suspended

• Conditions: NSCLC
• Interventions: Drug: Poziotinib; Drug: Docetaxel

• Registration Number: NCT05378763
• Lead Sponsor: Spectrum Pharmaceuticals, Inc

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.

Study Timeline

• Study First Submitted: 2022-05-09
• Study Start: 2022-05-12
• Study First Submitted QC: 2022-05-12
• Study First Posted: 2022-05-18
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-22
• Last Update Posted: 2025-05-23
• Primary Completion: 2027-12-25
• Study Completion: 2028-12-25

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 268

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Poziotinib 8 mg	Poziotinib	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.
Docetaxel 75 mg/m^2	Docetaxel	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Up to approximately 5 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to approximately 5 years	OS is defined as the time (in months) from the start of study treatment to the date of death due to any cause.
Objective Response Rate (ORR)	Up to approximately 5 years	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.
Disease Control Rate (DCR)	Up to approximately 5 years	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.

Trial Locations

Locations (1)

Bond Clinic, P.A.; 🇺🇸 Winter Haven, Florida, United States