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

Plain English Summary

SW-682 in Advanced Solid Tumors is a Phase 1 clinical trial sponsored by SpringWorks Therapeutics, Inc. studying Advanced Solid Tumor, Mesothelioma, Malignant. This trial tests a new drug called SW-682 for advanced solid tumors. It is for adults whose cancer has not responded to or has worsened after standard treatments. Participants will take SW-682 by mouth daily. Standard treatments or other clinical trials may be alternatives. The trial aims to enroll 186 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with advanced solid tumors, including mesothelioma, who have specific genetic mutations (Hippo pathway alterations) or NF2 mutations. Patients whose cancer has progressed after or is resistant to prior treatments like chemotherapy, immunotherapy, or targeted therapy. Must have measurable disease and a good general health status (ECOG performance status of 0 or 1). Cannot have active brain metastases, significant heart problems, or certain other medical conditions. This trial is studying Advanced Solid Tumor, Mesothelioma, Malignant, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the drug is, the best dose to use, and how well it shrinks tumors or controls cancer growth in patients with advanced solid tumors. The specific primary outcome measures are: Incidence of Adverse Events (Part 1 Only) (Up to 24 months); Maximum Tolerated Dose (Part 1 Only) (Up to 24 months); Recommended Dose for Expansion (Part 1 Only) (Up to 24 months); Objective Response Rate (Part 2 Only) (Up to 24 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a need for new treatments in advanced solid tumors, particularly those with specific genetic alterations in the Hippo pathway, where current options are limited. This research targets Advanced Solid Tumor, Mesothelioma, Malignant, where improved treatment options are needed.

Investor Insight

This Phase 1 trial is an early step to evaluate a novel targeted therapy, indicating potential for a new treatment option in a specific cancer subtype, with a focus on identifying a safe and effective Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if SW-682 is a suitable option for your specific cancer type and genetic profile. Understand that you will take the study drug by mouth daily for 28-day cycles. Be prepared for regular clinic visits for monitoring, tests, and potential biopsies. This trial is currently recruiting participants. The trial is being conducted at 8 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 186 participants

Interventions

• DRUG: SW-682 — SW-682 tablet administered orally
• DRUG: Combination Therapy — Appropriate combination therapy

Primary Outcomes

• Incidence of Adverse Events (Part 1 Only) (Up to 24 months)
• Maximum Tolerated Dose (Part 1 Only) (Up to 24 months)
• Recommended Dose for Expansion (Part 1 Only) (Up to 24 months)
• Objective Response Rate (Part 2 Only) (Up to 24 months)

Secondary Outcomes

• 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)

Full Eligibility Criteria

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)

Trial Locations

• SpringWorks Clinical Trial Site, Scottsdale, Arizona, United States
• UC San Diego Moores Cancer Center, La Jolla, California, United States
• USC/Norris Comprehensive Cancer Center, Los Angeles, California, United States
• SpringWorks Clinical Trial Site, 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

Frequently Asked Questions

Related Conditions

• Advanced Solid Tumors
• Mesothelioma, Malignant
• Cancer with Hippo Pathway Mutations
• Cancer with NF2 Mutations
• Metastatic Cancer
• Unresectable Cancer
• Refractory Cancer
• Progressed Cancer
• Targeted Therapy Resistance
• Chemotherapy Resistance

More Advanced Solid Tumor Trials

View all Advanced Solid Tumor clinical trials