A Study of THE-630 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

NCT05160168 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: THE630-21-101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 7

Brief Summary

This study will assess the safety, efficacy, and pharmacokinetics of THE-630 in participants with advanced gastrointestinal stromal tumors (GIST).

Conditions

Gastrointestinal Stromal Tumors (GIST); Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasm; Digestive System Disease; Gastrointestinal Diseases

Keywords

Gastrointestinal Stromal Tumor; GIST; KIT inhibitor; THE-630; THE630; THE 630; GIST TKI; GIST tyrosine kinase inhibitor; GIST treatments; GIST Imatinib relapse; GIST Sunitinib relapse; GIST Regorafenib relapse; GIST Ripretinib relapse; PDGFRA; KIT-mutant GIST; Advanced GIST

Outcome Measures

Primary Outcomes (5)

• Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  Up to 24 months after first dose

• Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630

  28 days

• Dose Escalation (Phase 1): Safety Analysis - Maximum Tolerated Dose (MTD) of Orally Administered THE-630

  The MTD is defined as the highest dose at which ≤1 of 6 DLT-assessment eligible patients experience a DLT within the first 28 days of treatment (end of Cycle 1).

  28 days

• Dose Escalation (Phase 1): Recommended Phase 2 Dose (RP2D) of Orally Administered THE-630

  The RP2D was expected to be equal to the MTD or less than the MTD, if aspects of tolerability or efficacy not encompassed by the MTD determination suggested utilizing a lower dose.

  28 days

• Expansion (Phase 2): Efficacy Assessment - For Each Expansion Phase Cohort (Cohorts 1, 2, and 3), Confirmed Objective Response Rate (ORR), According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Up to 24 months after first dose

Secondary Outcomes (26)

• Dose Escalation (Phase 1): Plasma Pharmacokinetic (PK) Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration)

  Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)

• Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax)

  Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)

• Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours)

  Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)

• Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t)

  Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)

• Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1

  Up to 24 months after first dose

Study Arms (4)

Dose Escalation

EXPERIMENTAL

Participants with unresectable or metastatic GIST who will receive orally administered THE-630.

Drug: THE-630

Expansion Cohort 1

EXPERIMENTAL

Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase.

Drug: THE-630

Expansion Cohort 2

EXPERIMENTAL

Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase.

Drug: THE-630

Expansion Cohort 3

EXPERIMENTAL

Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase.

Drug: THE-630

Interventions

THE-630 DRUG

Oral THE-630 administered once daily in a continuous regimen

Dose Escalation; Expansion Cohort 1; Expansion Cohort 2; Expansion Cohort 3

Eligibility Criteria

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

You may qualify if:

• Male or female patient ≥18 years of age.
• For Dose Escalation Phase Cohorts (Phase 1):
• Have histologically- or cytologically-confirmed unresectable or metastatic GIST.
• Have progressed on or are intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib.
• For Expansion Phase Cohorts (Phase 2):
• Cohort 1:
• Have histologically- or cytologically confirmed unresectable or metastatic GIST.
• Have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib.
• Cohort 2:
• Have histologically- or cytologically confirmed unresectable or metastatic GIST.
• Have progressed on or are intolerant to imatinib and sunitinib. Patients in this cohort are allowed to have received up to 1 additional line of therapy in the advanced/metastatic setting.
• Cohort 3:
• Have histologically- or cytologically confirmed unresectable or metastatic GIST.
• Have progressed on or are intolerant to imatinib (including in the adjuvant setting).
• Have not received additional systemic therapy for advanced GIST.

You may not qualify if:

• Received systemic anticancer therapy (including cytotoxic chemotherapy, investigational agent, antineoplastic monoclonal antibodies, or immunotherapy) less than 5 half-lives or 14 days (whichever is shorter) prior to the first dose of study drug.
• Patients known to be both KIT and PDGFRA wild-type.
• Received radiotherapy within 14 days prior to the first dose of study drug.
• Major surgical procedure within 28 days of the first dose of study drug. Minor surgical procedures such as central venous catheter placement or minimally invasive biopsy are allowed.
• Have known untreated or active central nervous system metastases.
• lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's formula (QTcF) \>470 msec at screening, or history of long QTc syndrome.
• Have significant, uncontrolled, or active cardiovascular disease, including, but not restricted to:
• Myocardial infarction (MI) within 6 months prior to the first dose of study drug
• Unstable angina within 6 months prior to first dose of study drug
• Symptomatic congestive heart failure (New York Heart Association classes II-IV) within 6 months prior to first dose of study drug
• Clinically significant, uncontrolled atrial arrhythmia (as determined by the Investigator)
• Any history of ventricular arrhythmia
• Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug
• Uncontrolled hypertension at study entry. Patients with hypertension should be under treatment on study entry to control blood pressure.
• Have an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics.

Sponsors & Collaborators

• Theseus Pharmaceuticals: lead

Study Sites (7)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Neoplasms by Site

Limitations and Caveats

The Sponsor made a business decision to terminate the trial early due to observed dose limiting toxicities at dose levels that are below the target THE-630 exposure (set by preclinical studies) required for pan KIT variant inhibition in GIST patients. Therefore, several of the outcome measures could not be evaluated.

Results Point of Contact

• Title: Stew Kroll
• Organization: Theseus Pharmaceuticals (a subsidiary of Concentra Biosciences)

skroll@concentrabiosciences.com

(650) 576-9679

Study Officials

• Stew Kroll

  Theseus Pharmaceuticals (a subsidiary of Concentra Biosciences)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 16, 2021
• Study Start: January 3, 2022
• Primary Completion: February 2, 2024
• Study Completion: February 2, 2024
• Last Updated: June 5, 2024
• Results First Posted: June 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)