A Study of TAS3351 in NSCLC Patients With EGFRmt

NCT05765734 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 100730102022-502595-23-00
• Study Type: interventional
• Target: 18
• Locations: 5 countries
• Sites: 8

Brief Summary

This is a first-in-human, open label, Phase 1/2 study to investigate the safety and efficacy of TAS3351 in participants with advanced or metastatic non-small cell lung cancer (NSCLC) harboring an acquired C797S epidermal growth factor receptor (EGFR) mutation.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; NSCLC; EGFR mutation; C797S mutation; TAS3351

Outcome Measures

Primary Outcomes (4)

• Part A1: Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAE)

  An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that started or worsened at the time of or after the first dose of study drug administration and within 30 days after the last dose of study drug and did not necessarily have a causal relationship to the use of the study drug.

  From first dose of the study drug up to 30 days after last dose (up to 21.7 months)

• Part A1: Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLTs were defined as adverse events (AEs) graded by Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) assessed by the Investigator to be related to study treatment administration during Cycle 1 \& included:Hematologic Toxicity;grade 4 neutropenia greater than\[\>\]7days; febrile neutropenia (absolute neutrophil count \[ANC\] less than(\<)1000 per cubic millimeter (1000/mm3) with fever greater than or equal to(≥)38.3 degree celsius (°C) or fever ≥38.0°C for \> 1hour); grade 4 thrombocytopenia, Hepatic Toxicity: grade ≥3 total bilirubin \>7days; grade 4 total bilirubin; Renal Toxicity:creatinine clearance(CrCl)\<30 milliliters per minute (mL/min) for \> 3days despite supportive care;Other Nonhematologic Toxicity:grade ≥3 nonhematologic toxicity with: grade 3 nausea, vomiting, diarrhea, or hyperglycemia, prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Any death not clearly attributed to the underlying disease or extraneous causes.

  Cycle 1 (cycle length = 21 days)

• Part B: Dose Expansion: Percentage of Participants With Objective Response Rate (ORR) by Independent Central Review (ICR)

  ORR was the proportion of participants experiencing a best overall response of partial response (PR) or complete response (CR) according to response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1) criteria. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to less than (\<)10 millimeters (mm).

  Up to 21.7 months

• Part C: Phase 2: Percentage of Participants With ORR by ICR

  ORR was the proportion of participants experiencing a PR or CR according to RECIST v1.1 criteria. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10mm.

  Up to approximately 21.7 months

Secondary Outcomes (28)

• Part A1: Dose Escalation: Percentage of Participants With ORR

  From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)

• Part A1: Dose Escalation: Duration of Response (DoR)

  From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)

• Part A1: Dose Escalation: Percentage of Participants Exhibiting Disease Control Rate (DCR)

  From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)

• Part A2: Backfill: Number of Participants Exhibiting Progression Free Survival (PFS)

  From first dose of the study drug up to 30 days after the last dose (up to 21.7 months)

• Part A2: Backfill: Number of Participants Exhibiting Overall Survival (OS)

  From first dose of the study drug up to 30 days after the last dose (up to 21.7 months)

Study Arms (9)

Part A1: Dose Escalation: 50 mg

EXPERIMENTAL

Participants received TAS3351 50 milligrams (mg), tablets, orally, once daily (QD), on Days 1-21 of each 21-day cycle, for maximum duration of 66 days.

Drug: TAS3351

Part A1: Dose Escalation: 100 mg

EXPERIMENTAL

Participants received TAS3351 100 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 126 days.

Drug: TAS3351

Part A1: Dose Escalation: 200 mg

EXPERIMENTAL

Participants received TAS3351 200 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 94 days.

Drug: TAS3351

Part A1: Dose Escalation: 350 mg

EXPERIMENTAL

Participants received TAS3351 350 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 46 days.

Drug: TAS3351

Part A1: Dose Escalation: 500 mg

EXPERIMENTAL

Participants received TAS3351 500 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 87 days.

Drug: TAS3351

Part A1: Dose Escalation: 700 mg

EXPERIMENTAL

Participants were to receive TAS3351 700 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle.

Drug: TAS3351

Part A2: Backfill

EXPERIMENTAL

Participants were to be enrolled in Part A2 (backfill) when a dose level in Part A1 was determined to be safe and preliminary antitumor activity was observed.

Drug: TAS3351

Part B: Dose Expansion

EXPERIMENTAL

.NSCLC participants with C797S EGFR mutations were planned for enrollment in Part B (dose expansion) and were to receive the recommended Phase 2 dose established in Part A.

Drug: TAS3351

Part C: Phase 2

EXPERIMENTAL

NSCLC participants with C797S EGFR mutations were planned for enrollment in Part C (Phase 2) and were to receive the recommended Phase 2 dose established in Part A

Drug: TAS3351

Interventions

TAS3351 DRUG

Oral tablets.

Part A1: Dose Escalation: 100 mg; Part A1: Dose Escalation: 200 mg; Part A1: Dose Escalation: 350 mg; Part A1: Dose Escalation: 50 mg; Part A1: Dose Escalation: 500 mg; Part A1: Dose Escalation: 700 mg; Part A2: Backfill; Part B: Dose Expansion; Part C: Phase 2

Eligibility Criteria

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

You may qualify if:

• Locally advanced, non-resectable or metastatic NSCLC
• Have adequate organ function
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Has tumor tissue available to allow for analysis of EGFRmt status
• Dose Escalation:
• Has any EGFRmt status
• Dose Escalation back-fill part, Dose Expansion and Phase II:
• Has any sensitizing EGFRmt and a confirmed C797S EGFRmt
• Has measurable disease per response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1)

You may not qualify if:

• Participating in medical research not compatible with this study
• Symptomatic and unstable central nervous system (CNS) metastases
• Have not recovered from prior cancer treatment
• Have a significant cardiac condition
• Are a pregnant or breastfeeding female
• A serious illness or medical condition
• Unable to swallow or digest pills

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (8)

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology - Virginia

Fairfax, Virginia, 22031, United States

Location

Institut Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Leiden University Medical Center (LUMC)

Leiden, 2333ZA, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was terminated by the Sponsor during Part A1 for strategic reasons. As a result, no participants were further enrolled in Parts A1 dose expansion for 700 mg, A2, B, or C of the study and therefore these parts were not conducted.

Results Point of Contact

• Title: Taiho
• Organization: Taiho Oncology, Inc.

clinicaltrialinfo@taihooncology.com

609-250-7336

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: March 13, 2023
• Study Start: May 25, 2023
• Primary Completion: March 14, 2025
• Study Completion: March 14, 2025
• Last Updated: April 2, 2026
• Results First Posted: April 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); JP (2); NL (1); FR (1); US (3)