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
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
Study locations (8)
SpringWorks Clinical Trial Site
Scottsdale, Arizona, 85258
UC San Diego Moores Cancer Center
La Jolla, California, 92093
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
SpringWorks Clinical Trial Site
Los Angeles, California, 90095
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Knight Cancer Institute Clinical Trials
Portland, Oregon, 97239
Mary Crowley Cancer Research
Dallas, Texas, 75230
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030