SW-682 in Advanced Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorSpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
About this trial
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
This trial does not accept healthy volunteersQualifiers
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
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).
Disqualifiers
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
Trial design
Design model
Sequential
Treatments tested in this trial
SW-682
DrugSW-682 tablet administered orally
Combination Therapy
DrugAppropriate combination therapy
Treatment groups
186 Participants
are divided into 5 treatment groupsGroup A: Phase 1 Dose Escalation Cohorts Ranging in DoseExperimental treatment 1 intervention
Group B: Part 2 Dose Expansion Cohort 1Experimental treatment 1 intervention
Group C: Part 2 Dose Expansion Cohort 2Experimental treatment 1 intervention
Group D: Part 2 Dose Expansion Cohort 3Experimental treatment 1 intervention
Group E: Part 2 Dose Expansion Cohort 4Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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)
Time frame
Up to 24 months2
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.
Time frame
Up to 24 months3
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.
Time frame
Up to 24 months4
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.
Time frame
Up to 24 monthsSecondary outcomes
1
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.
Time frame
Up to 24 months2
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.
Time frame
Up to 24 months3
Disease Control Rate
Disease control rate (DCR), defined as the percentage of participants with CR, PR, or stable disease (SD) after starting study treatment.
Time frame
Up to 24 months4
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.
Time frame
Up to 24 monthsSponsors and contacts
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Source ClinicalTrials.gov