A Phase 1 interventional study of SW-682 and Combination Therapy in Advanced Solid Tumor and Mesothelioma, Malignant, sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany. Recruiting at 8 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-02.
Sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany · Phase 1, Interventional, and Treatment
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.
Key Inclusion Criteria:
Part 1: must have one of the following:
Part 2: must have the tumor histology and oncogenic mutation or genomic aberration specific to each dose expansion cohort defined below:
Key Exclusion Criteria:
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
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
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
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
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
SW-682 tablet administered orally
Appropriate combination therapy
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
Change in plasma and urine concentrations of SW-682
Plasma and urine concentrations of SW-682 and any relevant metabolite(s) will be measured to evaluate systemic exposures and renal elimination.
Time frame: Up to 24 months
Objective Response Rate (Part 1 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
Disease Control Rate
Disease control rate (DCR), defined as the percentage of participants with CR, PR, or stable disease (SD) after starting study treatment.
Time frame: Up to 24 months
Duration of Response
Duration of response (DoR), defined as the time from response (CR + PR using RECIST v1.1, mRECIST and/or (GCIG) criteria for CA-125 response in ovarian cancer, as applicable) to disease progression and/or death, whichever occurs first.
Time frame: Up to 24 months
Progression-Free Survival
Progression-free survival (PFS), defined as the time from the date of the first administration of study treatment to the first documented disease progression per RECIST v1.1, mRECIST, and/or GCIG CA-125, as applicable, or death due to any cause, whichever occurs first.
Time frame: Up to 24 months
Plan to share: No — IPD will not be shared for Phase I interventional or observational studies. Further information on how to request data can be found on our website bit.ly/IPD21.
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SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany