SW-682 in Advanced Solid Tumors
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
1 other identifier
interventional
186
1 country
8
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2024
Typical duration for phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2024
CompletedFirst Posted
Study publicly available on registry
February 9, 2024
CompletedStudy Start
First participant enrolled
July 31, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 18, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 18, 2027
July 17, 2026
July 1, 2026
2.5 years
February 1, 2024
July 15, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
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)
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.
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.
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.
Up to 24 months
Secondary Outcomes (5)
Change in plasma and urine concentrations of SW-682
Up to 24 months
Objective Response Rate (Part 1 Only)
Up to 24 months
Disease Control Rate
Up to 24 months
Duration of Response
Up to 24 months
Progression-Free Survival
Up to 24 months
Study Arms (5)
Phase 1 Dose Escalation Cohorts Ranging in Dose
EXPERIMENTALParticipants 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 1
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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.
Part 2 Dose Expansion Cohort 3
EXPERIMENTALParticipants 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 4
EXPERIMENTALParticipants 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.
Interventions
SW-682 tablet administered orally
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
HonorHealth Research Institute
Scottsdale, Arizona, 85258, United States
USC Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, 90033, United States
UC San Diego Moores Cancer Center
Sacramento, California, 92093, United States
UCLA Hematology-Oncology - Santa Monica
Santa Monica, California, 90404, United States
University Hospital of Cleveland
Cleveland, Ohio, 44106, United States
Oregon Health and Science University, Knight Cancer Institute - Marquam Hill
Portland, Oregon, 97239, United States
Mary Crowley Research Center US Oncology
Dallas, Texas, 75230, United States
U.T. MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Responsible
SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 1, 2024
First Posted
February 9, 2024
Study Start
July 31, 2024
Primary Completion (Estimated)
January 18, 2027
Study Completion (Estimated)
January 18, 2027
Last Updated
July 17, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will not share
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.