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RecruitingInterventionalPhase 1

A Phase 1a/1b Dose Escalation, Dose Expansion Study of SW-682 in Participants With Advanced Solid Tumors Enriched for Those With Hippo Pathway Mutations

NCT ID: NCT06251310Sponsor: SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, GermanyLast updated: 2026-05-08

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.

Arms & interventions

  • DrugSW-682

    SW-682 tablet administered orally

  • DrugCombination Therapy

    Appropriate combination therapy

Outcome measures

Primary

  • 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)

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: Up to 24 months

Secondary

  • Change in plasma and urine concentrations of SW-682

    Time frame: Up to 24 months

  • Objective Response Rate (Part 1 Only)

    Time frame: Up to 24 months

  • Disease Control Rate

    Time frame: Up to 24 months

  • Duration of Response

    Time frame: Up to 24 months

  • Progression-Free Survival

    Time frame: Up to 24 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (8)

SpringWorks Clinical Trial Site

Scottsdale, Arizona, 85258

Recruiting
Nurse Navigation Team · Contact
Nurse Navigation Team · Contact
Muhammad R Khawaja, MD · Principal Investigator

UC San Diego Moores Cancer Center

La Jolla, California, 92093

Recruiting
Katherine Velasco · Contact
Sandip Patel, MD · Principal Investigator

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Recruiting
Xiomara Menendez, RN · Contact
Diana Hanna, MD · Contact

SpringWorks Clinical Trial Site

Los Angeles, California, 90095

Recruiting
Jacqueline Banuelos Murillo · Contact
Arun S Singh, MD · Principal Investigator

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

Recruiting
Afshin Dowlati, MD · Contact
Afshin Dowlati, MD · Principal Investigator

Knight Cancer Institute Clinical Trials

Portland, Oregon, 97239

Recruiting
Shivaani Kummar · Principal Investigator

Mary Crowley Cancer Research

Dallas, Texas, 75230

Recruiting
Douglas Orr, MD · Contact
Douglas Orr, MD · Principal Investigator

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Ileana Gutierrez · Contact
Timothy Yap, MD · Principal Investigator