SW-682 in Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06251310
• Other study ID #: TEAD-AST-101
• Status: Recruiting
• Phase: Phase 1
• Start date: July 2024
• Est. completion date: June 2030

Study information

• Verified date: June 2024
• Source: SpringWorks Therapeutics, Inc.
• Contact: SpringWorks Clinical
• Phone: 877-279-4870
• Email: clinical[@]springworkstx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: June 2030
• Est. primary completion date: January 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Mesothelioma
• Mesothelioma, Malignant

Intervention

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

Locations

Country	Name	City	State
United States	SpringWorks Clinical Trial Site	Cleveland	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	SpringWorks Clinical Trial Site	Houston	Texas
United States	SpringWorks Clinical Trial Site	La Jolla	California
United States	SpringWorks Clinical Trial Site	Los Angeles	California
United States	SpringWorks Clinical Trial Site	Los Angeles	California
United States	SpringWorks Clinical Trial Site	Portland	Oregon
United States	SpringWorks Clinical Trial Site	Scottsdale	Arizona
United States	SpringWorks Clinical Trial Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
SpringWorks Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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