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

Overview

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.

Interventions

• Drug SW-682
  SW-682 tablet administered orally
• Drug Combination Therapy
  Appropriate combination therapy

Primary outcome measures

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

Secondary outcome measures (5)

• Change in plasma and urine concentrations of SW-682 [Time frame: Up to 24 months]
• Objective Response Rate (Part 1 Only) [Time frame: Up to 24 months]
• Disease Control Rate [Time frame: Up to 24 months]
• Duration of Response [Time frame: Up to 24 months]
• Progression-Free Survival [Time frame: Up to 24 months]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• HonorHealth Research Institute — Scottsdale
• USC Norris Comprehensive Cancer Center and Hospital — Los Angeles
• UC San Diego Moores Cancer Center — Sacramento
• UCLA Hematology-Oncology - Santa Monica — Santa Monica
• University Hospital of Cleveland — Cleveland
• Oregon Health and Science University, Knight Cancer Institute - Marquam Hill — Portland
• Mary Crowley Research Center US Oncology — Dallas
• U.T. MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT06251310 · TEAD-AST-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗