Study of Poziotinib in Japanese Patients With NSCLC

NCT04402008 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: SPI-POZ-104
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 1/2, open-label, multicenter study to determine dose, tolerability, safety and efficacy of poziotinib in Japanese patients non-small cell lung cancer (NSCLC).

Conditions

NSCLC

Keywords

EGFR; HER2; Exon 20 insertion mutation

Outcome Measures

Primary Outcomes (2)

• Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT was any of the following treatment-related adverse events occurring during Cycle 1, Non-Hematological Toxicity: Grade 3 or higher toxicity except for alopecia; Grade 3 or higher nausea, vomiting, and diarrhea despite medical intervention. Hematological Toxicity: Grade 4 or higher neutropenia for ≥7 days; Febrile neutropenia with a single temperature of \>38.3°C or a sustained temperature of ≥38°C; Neutropenic infection: Grade 3 or higher infection accompanying Grade 4 neutropenia; Grade 4 thrombocytopenia or any grade thrombocytopenia requiring platelet transfusion.

  Cycle 1 (Day 1-28)

• Phase 2: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with best response i.e confirmed complete response (CR) and partial response (PR) as assessed by the investigator using local radiology evaluation according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.

  Up to 461 days

Secondary Outcomes (5)

• Phase 2: Disease Control Rate (DCR)

  Up to 461 days

• Phase 2: Duration of Response (DoR)

  Up to 461 days

• Phase 2: Progression Free Survival (PFS)

  Up to 461 days

• Phase 1: Plasma Concentration of Poziotinib and M1, M2 Metabolites

  Cycle 1, Day 1 and Day 13

• Phase 1 and 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAE)

  Up to 40 days after the last dose of the study drug (Up to 461 days)

Other Outcomes (1)

• Phase 2: Exploratory - Overall Survival

  2 years

Study Arms (3)

Phase 1: Once Daily Dosing

EXPERIMENTAL

Dose finding at 8 mg, 12 mg, or 16 mg of poziotinib once daily in 28-day treatment cycles.

Drug: Poziotinib Once Daily Dosing

Phase 1: Twice Daily Dosing

EXPERIMENTAL

Dose finding at 4 mg, 6 mg, or 8 mg of poziotinib twice daily in 28-day treatment cycles.

Drug: Poziotinib Twice Daily Dosing

Phase 2: Once Daily Dosing or Twice Daily Dosing

EXPERIMENTAL

Once Daily or Twice Daily Dosing as determined in Phase 1 in 28-day treatment cycles. Cohort 1: EGFR exon 20 insertion mutations Cohort 2: HER2 exon 20 insertion mutations

Drug: Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1

Interventions

Poziotinib Once Daily Dosing DRUG

The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

Phase 1: Once Daily Dosing

Poziotinib Twice Daily Dosing DRUG

The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

Phase 1: Twice Daily Dosing

Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1 DRUG

The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

Phase 2: Once Daily Dosing or Twice Daily Dosing

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
• Previously treated patient with histologically or cytologically confirmed (archival tissue accepted) locally advanced or metastatic non-small cell lung cancer (NSCLC) and is not a candidate for definitive therapy
• Phase 1: No test for mutational status is required
• Phase 2: Documented EGFR or HER2 exon 20 insertion mutations (including duplication mutations) in NSCLC patients
• Prior treatment status:
• Phase 1: Patient with refractory NSCLC to available standard therapies
• Phase 2: Progression after at least one systemic therapy for locally advanced or metastatic disease
• Patient has measurable NSCLC disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Metastatic lesions in bone, central nervous system (CNS), or in brain cannot be used for target lesions.
• Patient has recovered from prior systemic therapy for metastatic disease to Grade ≤1 for non-hematologic toxicities (except for Grade ≤2 peripheral neuropathy) and has adequate hematologic, hepatic, and renal function at Baseline

You may not qualify if:

• Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks prior to Cycle 1, Day 1; local radiation therapy for bone pain may be allowed
• Patient has used strong inhibitors/inducers of CYP3A4 and CYP2D6 within 1 month prior to Cycle 1, Day 1
• Patient has had another primary malignancy within 3 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ
• Patient is pregnant or breastfeeding
• Phase 2 : Patient has had previous treatment with poziotinib. The currently approved tyrosine kinase inhibitors (TKIs) that are not considered to be exon 20 insertion-selective are permissible

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead

Study Sites (3)

National Cancer Center East

Kashiwa, Chiba, 277-8577, Japan

Location

Osaka City General Hospital

Miyakojima-ku, Osaka, 534-0021, Japan

Location

Shizuoka Cancer Center

Sunto District, Shizuoka, 411-8777, Japan

Location

MeSH Terms

Interventions

Clinical Trials, Phase I as Topic

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Limitations and Caveats

The study was prematurely terminated for business reasons and not related to safety.

Results Point of Contact

• Title: Howard Franklin, MD
• Organization: Assertio Holdings

Hfranklin@assertiotx.com

224 419 7106

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 will have two randomized, parallel dose groups comparing daily dosing and twice daily dosing at 3 dose levels. Phase 2 will be a single dose group evaluating the safety and efficacy of the dose determined in Phase 1 in 2 Cohorts. Cohort 1: EGFR exon 20 insertion mutations and Cohort 2: HER2 exon 20 insertion mutations.

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: May 26, 2020
• Study Start: June 23, 2020
• Primary Completion: February 15, 2023
• Study Completion: February 15, 2023
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3)