Study of Poziotinib in Japanese Patients With NSCLC

A Phase 1/2 Dose Finding Study of Poziotinib in Japanese Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

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).

Study Overview

• Status: Terminated
• Conditions: NSCLC
• Intervention / Treatment: Drug: Poziotinib Once Daily Dosing; Drug: Poziotinib Twice Daily Dosing; Drug: Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1

Detailed Description

This is a Phase 1/2, open-label, multicenter study in Japanese patients with locally advanced or metastatic NSCLC. This study will be conducted in two parts. Phase 1 is designed to observe the maximum tolerated dose (MTD) or maximum administered dose (MAD) of poziotinib when administered once daily or twice daily. Phase 2 will evaluate the safety and efficacy of the dose determined in Phase 1. Study participation includes a 30 day screening period, up to 24 months of treatment, and long-term follow-up for a maximum of 24 months after discontinuation of study treatment.

Phase 1 will enroll up to 36 patients into a dose finding study with two parallel, randomized dose groups. Each group will undergo a dose-finding scheme using a 3+3 design with the assessment of dose-limiting toxicities (DLTs) at up to three dose levels. Patients will be randomized into once daily (QD) or twice daily (BID) dose groups. The DLT assessment will be conducted in the first cycle of treatment and therefore, poziotinib dose modifications are not permitted during this cycle. Patients will be hospitalized for the first 2 weeks.

Phase 2 will enroll 40 additional NSCLC patients with epidermal growth factor receptor (EGFR) (20 patients) or human epidermal growth factor 2 (HER2) (20 patients) exon 20 insertion mutations. Efficacy and safety of the dose and dosing regimen determined in Phase 1 will be evaluated. All patients will be treated in 28-day cycles for up to 24 months.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center East
  • Osaka
    • Miyakojima-ku, Osaka, Japan, 534-0021
      • Osaka City General Hospital
  • Shizuoka
    • Sunto District, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Once Daily Dosing; Dose finding at 8 mg, 12 mg, or 16 mg of poziotinib once daily in 28-day treatment cycles.	Drug: Poziotinib Once Daily Dosing; The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Experimental: Phase 1: Twice Daily Dosing; Dose finding at 4 mg, 6 mg, or 8 mg of poziotinib twice daily in 28-day treatment cycles.	Drug: Poziotinib Twice Daily Dosing; The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
Experimental: Phase 2: Once Daily Dosing or Twice Daily Dosing; 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; The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Disease Control Rate (DCR)	The percentage of participants who achieve CR, PR, and stable disease (SD) by the best response from the first dose of poziotinib to the end of the study as assessed by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10 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. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.	Up to 461 days
Phase 2: Duration of Response (DoR)	Duration of response was defined as the time from the date that measurement criteria are first met for CR or PR until the first subsequent date that progressive disease as assessed by the investigator according to RECIST v1.1 or death is documented. 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 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. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.	Up to 461 days
Phase 2: Progression Free Survival (PFS)	PFS was the number of days from the treatment start date to the date of first documented disease progression or death from any cause. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in sum of diameters (SOD) from previous smallest SOD on study, and an absolute increase of ≥5mm.	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)	TEAEs are AEs that occur from the first dose of study treatment until 40 days after the last dose of study treatment. An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.	Up to 40 days after the last dose of the study drug (Up to 461 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Exploratory - Overall Survival	The number of days from the treatment start date to the date of death due to any cause.	2 years

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2020
• Primary Completion (Actual): February 15, 2023
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (Actual): May 26, 2020

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: May 29, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: HER2; EGFR; Exon 20 insertion 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
• Other Study ID Numbers: SPI-POZ-104

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