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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
186
SW-682 tablet administered orally
Appropriate combination therapy
SpringWorks Clinical Trial Site
Scottsdale, Arizona, United States
RECRUITINGUC San Diego Moores Cancer Center
La Jolla, California, United States
RECRUITINGUSC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGSpringWorks Clinical Trial Site
Los Angeles, California, United States
RECRUITINGUniversity Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
RECRUITINGKnight Cancer Institute Clinical Trials
Portland, Oregon, United States
RECRUITINGMary Crowley Cancer Research
Dallas, Texas, United States
RECRUITINGThe University of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGIncidence 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
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