SW-682 in Advanced Solid Tumors

NCT06251310 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TEAD-AST-101
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 8

Brief Summary

This is a first-in-human (FIH), Phase 1a/1b open-label, multicenter, dose escalation and dose expansion study of SW-682 in adult participants with metastatic or unresectable advanced solid tumors with or without Hippo pathway alterations that are refractory to, or have progressed, during or after appropriate prior systemic anticancer therapy, including chemotherapy, immunotherapy, radiation therapy or targeted therapy, or for which no treatment is available, or prior standard of care (SOC) therapy was not tolerated and for which there is no further SOC treatment available. The study includes a Part 1 (Phase 1a) dose escalation phase and a Part 2 (Phase 1b) dose expansion to optimize the dose to be used for further development. All participants will self-administer SW-682 by mouth in 28-day cycles.

Conditions

Advanced Solid Tumor; Mesothelioma, Malignant

Outcome Measures

Primary Outcomes (4)

• Incidence of Adverse Events (Part 1 Only)

  Safety and tolerability endpoint evaluation via incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment emergent adverse events (TEAE)

  Up to 24 months

• Maximum Tolerated Dose (Part 1 Only)

  The maximum tolerated dose (MTD) for SW-682, if any, will be based on safety and tolerability during the first 28 days of treatment in Cycle 1.

  Up to 24 months

• Recommended Dose for Expansion (Part 1 Only)

  The recommended dose for expansion (RDE) will be determined based on all safety, tolerability, pharmacokinetics (PK), preliminary antitumor efficacy, and other available data from Part 1 of the study.

  Up to 24 months

• Objective Response Rate (Part 2 Only)

  Objective response rate (ORR), defined as the proportion of participants with confirmed CR or PR using RECIST v1.1, mRECIST for mesothelioma, and/or GCIG CA-125 for ovarian cancer, as applicable, assessed by the investigator.

  Up to 24 months

Secondary Outcomes (5)

• Change in plasma and urine concentrations of SW-682

  Up to 24 months

• Objective Response Rate (Part 1 Only)

  Up to 24 months

• Disease Control Rate

  Up to 24 months

• Duration of Response

  Up to 24 months

• Progression-Free Survival

  Up to 24 months

Study Arms (5)

Phase 1 Dose Escalation Cohorts Ranging in Dose

EXPERIMENTAL

Participants with advanced solid tumors with or without Hippo pathway mutations will receive SW-682 tablets administered orally in continuous 28-day cycles. SW-682 dosage and frequency of administration will vary by cohort.

Drug: SW-682

Part 2 Dose Expansion Cohort 1

EXPERIMENTAL

Participants with mesothelioma with or without NF2 mutations will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data.

Drug: SW-682

Part 2 Dose Expansion Cohort 2

EXPERIMENTAL

Participants with advanced solid tumors with NF2 mutations will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data.

Drug: SW-682

Part 2 Dose Expansion Cohort 3

EXPERIMENTAL

Participants with advanced solid tumors with other Hippo pathway mutations identified during Part 1 (Phase 1a) dose escalation will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data.

Drug: SW-682

Part 2 Dose Expansion Cohort 4

EXPERIMENTAL

Participants will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data, with appropriate combination therapy, identified based on Part 1 data.

Drug: SW-682; Drug: Combination Therapy

Interventions

SW-682 DRUG

SW-682 tablet administered orally

Part 2 Dose Expansion Cohort 1; Part 2 Dose Expansion Cohort 2; Part 2 Dose Expansion Cohort 3; Part 2 Dose Expansion Cohort 4; Phase 1 Dose Escalation Cohorts Ranging in Dose

Combination Therapy DRUG

Appropriate combination therapy

Part 2 Dose Expansion Cohort 4

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, metastatic, or unresectable solid cancer that has either not responded to or progressed during or after appropriate prior systemic anticancer therapy including chemotherapy, immunotherapy, radiation therapy, or appropriate targeted therapy, or for which there is no treatment available or prior SOC therapy was not tolerated and for which there is no further SOC treatment available
• Part 1: must have one of the following:
• Mesothelioma with or without NF2 mutations
• Advanced solid tumors with NF2 mutations
• Advanced solid tumors with other Hippo pathway mutations or fusions (e.g., FAT1, LATS1/2, YAP fusions; WWTR1-CAMTA1 in EHE).
• Part 2: must have the tumor histology and oncogenic mutation or genomic aberration specific to each dose expansion cohort defined below:
• Cohort 1: Participants with mesothelioma with or without NF2 mutations
• Cohort 2: Participants with advanced solid tumors with NF2 mutations
• Cohort 3: Participants with advanced solid tumors with other Hippo pathway mutations identified during Part 1 (Phase 1a) dose escalation
• Cohort 4: SW-682 with appropriate combination therapy.
• In both parts, participants should have known oncogenic mutation identified by Next Generation Sequencing or local assay
• Must have archival tumor tissue or agree to a fresh tumor biopsy at screening
• Measurable disease per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Adequate bone marrow, kidney, hepatic, and coagulation function

You may not qualify if:

• Evidence of symptomatic CNS metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression
• Clinically significant cardiac disease or abnormal cardiac parameters
• Preexistence or inheritance of a familial renal syndrome
• Concomitant non-anti-arrhythmic medications that are known to prolong the QTc interval
• Concomitant medicines that are known strong/moderate inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) and/or CYP1A2 within 14 days or 5 half-lives before the first dose of study treatment
• Concomitant medicines that are known sensitive substrates of CYP3A4, CYP2C19, CYP2D6, CYP1A2, and/or CYP2B6 within 14 days or 5 half-lives before the first dose of study treatment
• Concomitant medicines that are known sensitive substrates of PGP, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, MATE1, MATE2-K, OCT2
• Clinically significant active infection (bacterial, fungal, or viral)

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc.: lead

Study Sites (8)

SpringWorks Clinical Trial Site

Scottsdale, Arizona, 85258, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

SpringWorks Clinical Trial Site

Los Angeles, California, 90095, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Knight Cancer Institute Clinical Trials

Portland, Oregon, 97239, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Combined Modality Therapy

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

US Medical Information

CONTACT

888-275-7376; eMediUSA@emdserono.com

Study Design

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

Model Details: The study will be conducted in two sequential parts: Part 1 dose escalation and Part 2 dose expansion.

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: July 30, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)