SW-682 in Advanced Solid Tumors
- Conditions
- Advanced Solid TumorMesothelioma, Malignant
- Interventions
- Drug: Combination Therapy
- Registration Number
- NCT06251310
- Lead Sponsor
- SpringWorks Therapeutics, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 186
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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
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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).
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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.
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In both parts, participants should have known oncogenic mutation identified by Next Generation Sequencing or local assay
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Must have archival tumor tissue or agree to a fresh tumor biopsy at screening
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Measurable disease per RECIST 1.1
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
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Adequate bone marrow, kidney, hepatic, and coagulation function
Key
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 Dose Expansion Cohort 4 Combination Therapy 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. Phase 1 Dose Escalation Cohorts Ranging in Dose SW-682 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. Part 2 Dose Expansion Cohort 4 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. Part 2 Dose Expansion Cohort 3 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. Part 2 Dose Expansion Cohort 1 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. Part 2 Dose Expansion Cohort 2 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.
- Primary Outcome Measures
Name Time Method 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.
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)
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.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (Part 1 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.
Disease Control Rate Up to 24 months Disease control rate (DCR), defined as the percentage of participants with CR, PR, or stable disease (SD) after starting study treatment.
Duration of Response Up to 24 months 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.
Progression-Free Survival Up to 24 months 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.
Change in plasma and urine concentrations of SW-682 Up to 24 months Plasma and urine concentrations of SW-682 and any relevant metabolite(s) will be measured to evaluate systemic exposures and renal elimination.
Trial Locations
- Locations (7)
SpringWorks Clinical Trial Site
🇺🇸Nashville, Tennessee, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Knight Cancer Institute Clinical Trials
🇺🇸Portland, Oregon, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States