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

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: Mesothelioma, Malignant; Advanced Solid Tumor
• Intervention / Treatment: Drug: Combination Therapy; Drug: SW-682

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US Medical Information; Phone Number: 888-275-7376; Email: eMediUSA@emdserono.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • HonorHealth Research Institute
      • Principal Investigator: Muhammad R Khawaja, MD
      • Contact: Email: mkhawaja@honorhealth.com
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center and Hospital
      • Principal Investigator: Diana Hanna, MD
      • Contact: Email: diana.hanna@med.usc.edu
    • Sacramento, California, United States, 92093
      • Recruiting
      • UC San Diego Moores Cancer Center
      • Principal Investigator: Sandip Patel, MD
      • Contact: Email: sandippatel@ucsd.edu
    • Santa Monica, California, United States, 90404
      • Recruiting
      • UCLA Hematology-Oncology - Santa Monica
      • Principal Investigator: Arun S Singh, MD
      • Contact: Email: Asingh@mednet.ucla.edu
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospital of Cleveland
      • Principal Investigator: Afshin Dowlati, MD
      • Contact: Phone Number: 216-844-3951; Email: afshin.dowlati@uhhospitals.org
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University, Knight Cancer Institute - Marquam Hill
      • Principal Investigator: Shivaani Kummar
      • Contact: Email: kummar@ohsu.edu
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley Research Center US Oncology
      • Principal Investigator: Douglas Orr, MD
      • Contact: Phone Number: 972-566-3000; Email: Douglas.Orr@scri.com
    • Houston, Texas, United States, 77030
      • Recruiting
      • U.T. MD Anderson Cancer Center
      • Principal Investigator: Timothy Yap, MD
      • Contact: Email: TYap@mdanderson.org

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

5

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)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	Up to 24 months

Collaborators and Investigators

• 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

Publications and helpful links

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

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): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 7, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Therapeutics; Combined Modality Therapy
• Other Study ID Numbers: TEAD-AST-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No