Clinical trial NCT05378763: A Study of Poziotinib in Previously Treated Participants With Locally Advanced or Metastatic NSCLC Harboring HER2 Exon 20 Mutations
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)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: NSCLC
Keywords: Epidermal growth factor receptor (EGFR)
HER2
Exon 20 mutation
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2022-05-18
Enrollment: 268
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to approximately 5 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 5 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Winter Haven
country: United States
facility: Bond Clinic, P.A.
state: Florida
Study officials:
References: