SW-682 in Advanced Solid Tumors

NCT ID: NCT06251310

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-30
• Study Completion Date: 2030-06-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Dose Escalation Cohorts Ranging in Dose

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.

Group Type: EXPERIMENTAL

SW-682

Intervention Type: DRUG

SW-682 tablet administered orally

Part 2 Dose Expansion Cohort 1

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.

Group Type: EXPERIMENTAL

SW-682

Intervention Type: DRUG

SW-682 tablet administered orally

Part 2 Dose Expansion Cohort 2

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.

Group Type: EXPERIMENTAL

SW-682

Intervention Type: DRUG

SW-682 tablet administered orally

Part 2 Dose Expansion Cohort 3

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.

Group Type: EXPERIMENTAL

SW-682

Intervention Type: DRUG

SW-682 tablet administered orally

Part 2 Dose Expansion Cohort 4

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.

Group Type: EXPERIMENTAL

SW-682

Intervention Type: DRUG

SW-682 tablet administered orally

Combination Therapy

Intervention Type: DRUG

Appropriate combination therapy

Interventions

SW-682

SW-682 tablet administered orally

Intervention Type: DRUG

Combination Therapy

Appropriate combination therapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SpringWorks Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

SpringWorks Clinical Trial Site

Scottsdale, Arizona, United States

Site Status: RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status: RECRUITING

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status: RECRUITING

SpringWorks Clinical Trial Site

Los Angeles, California, United States

Site Status: RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status: RECRUITING

Knight Cancer Institute Clinical Trials

Portland, Oregon, United States

Site Status: RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status: RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

SpringWorks Clinical

Role: CONTACT

clinical@springworkstx.com

877-279-4870

Facility Contacts

Nurse Navigation Team

Role: primary

clinicaltrials@honorhealth.com

480-323-1791

Nurse Navigation Team

Role: backup

clinicaltrials@honorhealth.com

833-354-6667

Katherine Velasco

Role: primary

kcvelasco@health.ucsd.edu

858-822-5677

Xiomara Menendez, RN

Role: primary

Xiomara.Menendez@med.usc.edu

323-865-0212

Diana Hanna, MD

Role: backup

diana.hanna@med.usc.edu

Jacqueline Banuelos Murillo

Role: primary

jbanuelosillo@mednet.ucla.edu

310-633-8400 ext. 16068

Afshin Dowlati, MD

Role: primary

afshin.dowlati@uhhospitals.org

216-844-3951

Role: primary

trials@ohsu.edu

503-494-1080

Douglas Orr, MD

Role: primary

referral@marycrowley.org

972-566-3000

Ileana Gutierrez

Role: primary

ILGutierrez@mdanderson.org

713-563-2158

Other Identifiers

TEAD-AST-101

Identifier Type: -

Identifier Source: org_study_id