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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy 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)
Primary outcome measure(s)
Incidence of Adverse Events (Part 1 Only) — Up to 24 months Safety and tolerability endpoint evaluation via incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment emergent adverse events (TEAE)
Maximum Tolerated Dose (Part 1 Only) — Up to 24 months 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.
Recommended Dose for Expansion (Part 1 Only) — Up to 24 months 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.
Objective Response Rate (Part 2 Only) — Up to 24 months 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.
Trial sites (8)
Facility
City
Region
Status
HonorHealth Research Institute
Scottsdale
Arizona
Recruiting
USC Norris Comprehensive Cancer Center and Hospital
Los Angeles
California
Recruiting
UC San Diego Moores Cancer Center
Sacramento
California
Recruiting
UCLA Hematology-Oncology - Santa Monica
Santa Monica
California
Recruiting
University Hospital of Cleveland
Cleveland
Ohio
Recruiting
Oregon Health and Science University, Knight Cancer Institute - Marquam Hill
Portland
Oregon
Recruiting
Mary Crowley Research Center US Oncology
Dallas
Texas
Recruiting
U.T. MD Anderson Cancer Center
Houston
Texas
Recruiting
More SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany trials in the USA
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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