A Study of Pimitespib in Combination With Imatinib in Patients With GIST (CHAPTER-GIST-101)

NCT05245968 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 10058060
• Study Type: interventional
• Target: 78
• Locations: 5 countries
• Sites: 14

Brief Summary

This study consists of Dose escalation part and Expansion part. In Dose Escalation Part, the maximum tolerated dose of combination of pimitespib and imatinib in patients with gastrointestinal stromal tumors (GIST) who are judged to be refractory to imatinib, estimate the recommended dose, evaluate safety and pharmacokinetics, and observe the antitumor effect. Expansion part consists of 3 arms. In Arm A, the efficacy and safety will be evaluated, which of the combination of pimitespib and imatinib in patients with GIST who have failed imatinib at doses below the MTD determined in Dose Escalation Part. In Arm B, the efficacy and safety of pimitespib monotherapy will be evaluated and the therapeutic effect of imatinib administration after pimitespib will be evaluated in an exploratory manner. In Arm C, the efficacy and safety of sunitinib monotherapy will be evaluated as reference data.

Conditions

Gastrointestinal Stromal Tumors

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib

  At the end of Cycle 1 (each cycle is 28 days)

• Maximum tolerable dose (MTD) of pimitespib in combination with imatinib

  At the end of Cycle 1 (each cycle is 28 days)

• Progression-free survival (PFS)

  approximately 2 years

Secondary Outcomes (17)

• Overall survival (OS)

  approximately 2 years

• Overall response rate (ORR)

  approximately 2 years

• Disease control rate (DCR)

  approximately 2 years

• Duration of response (DoR)

  approximately 2 years

• Adverse event (AE)

  approximately 2 years

Study Arms (4)

Dose Escalation Part

EXPERIMENTAL

Pimitespib in combination with imatinib

Drug: Pimitespib; Drug: Imatinib

Expansion Part-A

EXPERIMENTAL

Pimitespib in combination with imatinib

Drug: Pimitespib; Drug: Imatinib

Expansion Part-B

EXPERIMENTAL

Pimitespib followed by imatinib

Drug: Pimitespib; Drug: Imatinib

Expansion Part-C

EXPERIMENTAL

Sunitinib

Drug: Sunitinib

Interventions

Pimitespib DRUG

Pimitespib will be administered orally in 5 consecutive days followed by 2 days off treatment (QD 5) on an empty stomach at least 1 hour before or 2 hours after a meal. The doses in the Dose Escalation Part will be 80, 120 (starting dose), and 160 mg. The doses used in Arm A will be MTD or recommended dose (RD) based on the information, including the safety and the pharmacokinetics (PK) data in the Dose Escalation Part. In Expansion Part-B, pimitespib will be administered with the starting dose of 160 mg daily.

Also known as: TAS-116

Dose Escalation Part; Expansion Part-A; Expansion Part-B

Imatinib DRUG

Imatinib will be administered orally, after a meal and large glass of water QD. The doses in Dose Escalation Part will be 400 mg or 300 mg (De-escalation). The doses used in Expansion Part-A will be MTD or RD based on information, including the safety and PK data in the Dose Escalation Part. In Expansion Part-B, imatinib will be administered post after pimitespib discontinuation with the starting dose of 400 mg daily.

Dose Escalation Part; Expansion Part-A; Expansion Part-B

Sunitinib DRUG

Sunitinib will be administered orally QD with a starting dose of 50 mg, on a schedule of 4 weeks on treatment followed by 2 weeks off, and will be taken with or without a meal in Expansion Part-C.

Expansion Part-C

Eligibility Criteria

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

You may qualify if:

• Provided written informed consent
• Histologically confirmed GIST
• Has radiographic progression based on RECIST 1.1 during or within 6 months of the last imatinib administration at enrollment. If surgery/radiotherapy has been performed, radiographic progression based on RECIST 1.1 with imatinib must have been observed after the last surgery /radiotherapy
• Has at least one measurable lesion based on the RECIST version 1.1, except lymph nodes (not dependent on size), which should be chosen as nontarget lesions;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

You may not qualify if:

• Corrected visual acuity \< 0.5 (using the International Visual Acuity Measurement Standard) for both eyes
• Received treatment with any other line of therapy besides imatinib for advanced GIST
• History of total gastrectomy and/or whole resection of the small intestine
• A serious illness or medical condition
• Previous or concurrent cancer that is distinct in primary disease or histology from cancer that is being evaluated in this study. However, any previous cancer curatively treated \> 5 years before the enrollment can be eligible
• Pregnancy or lactation (including lactation interruption)

Sponsors & Collaborators

• Taiho Pharmaceutical Co., Ltd.: lead

Study Sites (14)

Flinders Medical Center

Adelaide, Australia

Location

Alfred Health

Melbourne, Australia

Location

Beijing Cancer Hospital

Beijing, China

Location

Fudan University, Shanghai Cancer Center

Shanghai, China

Location

National Cancer Center Hospital East

Chiba, Japan

Location

Hokkaido University Hospital

Hokkaido, Japan

Location

Kumamoto University Hospital

Kumamoto, Japan

Location

Osaka University Hospital

Osaka, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, Japan

Location

National University Cancer Institute

Singapore, Singapore

Location

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Linkou District, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

TAS-116; Imatinib Mesylate; Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Taiho Pharmaceutical Co., Ltd.

  Taiho Pharmaceutical Co., Ltd.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 18, 2022
• Study Start: December 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: https://www.taiho.co.jp/en/science/policy/clinical\ trial\ information\ disclosure\ policy/index.html
• Access Criteria: Access to the clinical trial data is contingent upon approval of a proposed study protocol by an independent review panel and the execution of a data-sharing agreement with the researcher.

Locations

CN (2); JP (6); SG (1); AU (2); TW (3)