Clinical trial NCT06251310: SW-682 in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Mesothelioma, Malignant
Lead sponsor: SpringWorks Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-09
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study will be conducted in two sequential parts: Part 1 dose escalation and Part 2 dose expansion.
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Incidence of Adverse Events (Part 1 Only)
timeFrame: Up to 24 months
measure: Maximum Tolerated Dose (Part 1 Only)
timeFrame: Up to 24 months
measure: Recommended Dose for Expansion (Part 1 Only)
timeFrame: Up to 24 months
measure: Objective Response Rate (Part 2 Only)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Change in plasma and urine concentrations of SW-682
timeFrame: Up to 24 months
measure: Objective Response Rate (Part 1 Only)
timeFrame: Up to 24 months
measure: Disease Control Rate
timeFrame: Up to 24 months
measure: Duration of Response
timeFrame: Up to 24 months
measure: Progression-Free Survival
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: SpringWorks Clinical Trial Site
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: SpringWorks Clinical Trial Site
state: California
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Knight Cancer Institute Clinical Trials
state: Oregon
city: Nashville
country: United States
facility: SpringWorks Clinical Trial Site
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
References: