SW-682 in Advanced Solid Tumors
Purpose
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.
Conditions
- Advanced Solid Tumor
- Mesothelioma, Malignant
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
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 Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- The study will be conducted in two sequential parts: Part 1 dose escalation and Part 2 dose expansion.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
|
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. |
|
|
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. |
|
|
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. |
|
Recruiting Locations
USC Norris Comprehensive Cancer Center and Hospital
Los Angeles, California 90033
Los Angeles, California 90033
UCLA Hematology-Oncology - Santa Monica
Santa Monica, California 90404
Santa Monica, California 90404
University Hospital of Cleveland
Cleveland, Ohio 44106
Cleveland, Ohio 44106
Oregon Health and Science University, Knight Cancer Institute - Marquam Hill
Portland, Oregon 97239
Portland, Oregon 97239
Mary Crowley Research Center US Oncology
Dallas, Texas 75230
Dallas, Texas 75230
More Details
- Status
- Recruiting
- Sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany