SW-682 in Advanced Solid Tumors

June 17, 2026 updated by: SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

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

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

186

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Principal Investigator:
          • Sandip Patel, MD
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC Norris Comprehensive Cancer Center and Hospital
        • Principal Investigator:
          • Diana Hanna, MD
        • Contact:
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA Hematology-Oncology - Santa Monica
        • Contact:
        • Principal Investigator:
          • Arun S Singh, MD
    • Ohio
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University, Knight Cancer Institute - Marquam Hill
        • Principal Investigator:
          • Shivaani Kummar
        • Contact:
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75230
        • Recruiting
        • Mary Crowley Research Center US Oncology
        • Principal Investigator:
          • Douglas Orr, MD
        • Contact:
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 Dose Escalation Cohorts Ranging in Dose
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.
Drug: SW-682
SW-682 tablet administered orally
Experimental: Part 2 Dose Expansion Cohort 1
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.
Drug: SW-682
SW-682 tablet administered orally
Experimental: Part 2 Dose Expansion Cohort 2
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.
Drug: SW-682
SW-682 tablet administered orally
Experimental: Part 2 Dose Expansion Cohort 3
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.
Drug: SW-682
SW-682 tablet administered orally
Experimental: Part 2 Dose Expansion Cohort 4
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.
Drug: Combination Therapy
Appropriate combination therapy
Drug: SW-682
SW-682 tablet administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events (Part 1 Only)
Time Frame: 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)
Up to 24 months
Maximum Tolerated Dose (Part 1 Only)
Time Frame: 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.
Up to 24 months
Recommended Dose for Expansion (Part 1 Only)
Time Frame: 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.
Up to 24 months
Objective Response Rate (Part 2 Only)
Time Frame: 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.
Up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in plasma and urine concentrations of SW-682
Time Frame: 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.
Up to 24 months
Objective Response Rate (Part 1 Only)
Time Frame: 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.
Up to 24 months
Disease Control Rate
Time Frame: 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.
Up to 24 months
Duration of Response
Time Frame: 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.
Up to 24 months
Progression-Free Survival
Time Frame: 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.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Medical Responsible, SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 31, 2024

Primary Completion (Estimated)

January 18, 2027

Study Completion (Estimated)

January 18, 2027

Study Registration Dates

First Submitted

February 1, 2024

First Submitted That Met QC Criteria

February 1, 2024

First Posted (Actual)

February 9, 2024

Study Record Updates

Last Update Posted (Actual)

June 22, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TEAD-AST-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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