Recruiting
Phase 1

SW-682

Sponsor:

SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

Code:

NCT06251310

Conditions

Advanced Solid Tumor

Mesothelioma, Malignant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

SW-682

Combination Therapy

Study Details

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 ID

NCT06251310

Start date

Jul 31, 2024

Status verified date

Sep, 2026

Completion date

Jan 18, 2027

Anticipated

Primary completion date

Jan 18, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key 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

Key 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)

Study Design

Enrollment

186 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

Interventions

SW-682

SW-682 tablet administered orally

Combination Therapy

Appropriate combination therapy

Primary outcome measure

  • Incidence of Adverse Events (Part 1 Only) [ Time Frame: Up to 24 months ]
  • Maximum Tolerated Dose (Part 1 Only) [ Time Frame: Up to 24 months ]
  • Recommended Dose for Expansion (Part 1 Only) [ Time Frame: Up to 24 months ]
  • Objective Response Rate (Part 2 Only) [ Time Frame: Up to 24 months ]

Central Contacts and Locations

Central contacts

US Medical Information

888-275-7376eMediUSA@emdserono.com

Locations

HonorHealth Research Institute

Recruiting

Scottsdale, Arizona, United States, 85258

Contacts

mkhawaja@honorhealth.com

Principal Investigator:

Muhammad R Khawaja, MD

USC Norris Comprehensive Cancer Center and Hospital

Recruiting

Los Angeles, California, United States, 90033

Contacts

diana.hanna@med.usc.edu

Principal Investigator:

Diana Hanna, MD

UC San Diego Moores Cancer Center

Recruiting

Sacramento, California, United States, 92093

Contacts

sandippatel@ucsd.edu

Principal Investigator:

Sandip Patel, MD

UCLA Hematology-Oncology - Santa Monica

Recruiting

Santa Monica, California, United States, 90404

Contacts

Asingh@mednet.ucla.edu

Principal Investigator:

Arun S Singh, MD

University Hospital of Cleveland

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

216-844-3951afshin.dowlati@uhhospitals.org

Principal Investigator:

Afshin Dowlati, MD

Oregon Health and Science University, Knight Cancer Institute - Marquam Hill

Recruiting

Portland, Oregon, United States, 97239

Contacts

kummar@ohsu.edu

Principal Investigator:

Shivaani Kummar

Mary Crowley Research Center US Oncology

Recruiting

Dallas, Texas, United States, 75230

Contacts

972-566-3000Douglas.Orr@scri.com

Principal Investigator:

Douglas Orr, MD

U.T. MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

TYap@mdanderson.org

Principal Investigator:

Timothy Yap, MD

More Information

Sponsor

SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

Last update posted

Sep 2, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany on 2026-09-02.