Advanced Solid TumorPhase 1NCT06251310
SW-682 in Advanced Solid Tumors
A Phase 1 study testing SW-682 and Combination Therapy in people with Advanced Solid Tumor and Mesothelioma, Malignant, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 8 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Mesothelioma, Malignant
- What is being tested?
- SW-682 and Combination Therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 8 sitesUnited States
- Study dates
- 31 Jul 2024to 18 Jan 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 15Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 8 recruiting
- Recruiting
University Hospital of Cleveland
Cleveland, Ohio, 44106
216-844-3951, afshin.dowlati@uhhospitals.org
Afshin Dowlati, MD
- Recruiting
Mary Crowley Research Center US Oncology
Dallas, Texas, 75230
972-566-3000, Douglas.Orr@scri.com
Douglas Orr, MD
- Recruiting
U.T. MD Anderson Cancer Center
Houston, Texas, 77030
TYap@mdanderson.org
Timothy Yap, MD
- Recruiting
USC Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, 90033
diana.hanna@med.usc.edu
Diana Hanna, MD
- Recruiting
Oregon Health and Science University, Knight Cancer Institute - Marquam Hill
Portland, Oregon, 97239
kummar@ohsu.edu
Shivaani Kummar
- Recruiting
UC San Diego Moores Cancer Center
Sacramento, California, 92093
sandippatel@ucsd.edu
Sandip Patel, MD
- Recruiting
UCLA Hematology-Oncology - Santa Monica
Santa Monica, California, 90404
Asingh@mednet.ucla.edu
Arun S Singh, MD
- Recruiting
HonorHealth Research Institute
Scottsdale, Arizona, 85258
mkhawaja@honorhealth.com
Muhammad R Khawaja, MD
About this study
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
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
- Being tested
- SW-682, Combination Therapy
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SW-682Drug
SW-682 tablet administered orally
Combination TherapyDrug
Appropriate combination therapy
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose Escalation Cohorts Ranging in Dose | Experimental | 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. Receives: Drug: SW-682 |
| Part 2 Dose Expansion Cohort 1 | Experimental | 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. Receives: Drug: SW-682 |
| Part 2 Dose Expansion Cohort 2 | Experimental | 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. Receives: Drug: SW-682 |
| Part 2 Dose Expansion Cohort 3 | Experimental | 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. Receives: Drug: SW-682 |
| Part 2 Dose Expansion Cohort 4 | Experimental | 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. Receives: Drug: SW-682; Drug: Combination Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Up to 24 months
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.
Measured: Up to 24 months
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.
Measured: Up to 24 months
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.
Measured: Up to 24 months
Secondary outcomes (5)
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.
Measured: Up to 24 months
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.
Measured: Up to 24 months
Disease Control Rate
Disease control rate (DCR), defined as the percentage of participants with CR, PR, or stable disease (SD) after starting study treatment.
Measured: Up to 24 months
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.
Measured: Up to 24 months
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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2024
- Study start31 Jul 2024
- Primary completion18 Jan 2027 (estimated)
- Study completion18 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study will be conducted in two sequential parts: Part 1 dose escalation and Part 2 dose expansion.
- Masking
- None (open label)
- Enrolment
- 186 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06251310
- Sponsor's protocol ID
- TEAD-AST-101
- Status last verified
- Sep 2026
- First submitted
- 1 Feb 2024
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared for Phase I interventional or observational studies. Further information on how to request data can be found on our website bit.ly/IPD21.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06251310
- Acronym / sponsor ID
- TEAD-AST-101
- Conditions
- Advanced Solid Tumor, Mesothelioma, Malignant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 186 participants (estimated)
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2024 (actual)
- Primary completion
- 18 Jan 2027 (estimated)
- Study completion
- 18 Jan 2027 (estimated)
- First posted
- 9 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- The study will be conducted in two sequential parts: Part 1 dose escalation and Part 2 dose expansion.
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Dose Escalation Cohorts Ranging in Dose | Experimental | Drug: SW-682Participants 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. |
| Part 2 Dose Expansion Cohort 1 | Experimental | Drug: SW-682Participants 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. |
| Part 2 Dose Expansion Cohort 2 | Experimental | Drug: SW-682Participants 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. |
| Part 2 Dose Expansion Cohort 3 | Experimental | Drug: SW-682Participants 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. |
| Part 2 Dose Expansion Cohort 4 | Experimental | Drug: SW-682, Drug: Combination TherapyParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- Part 2: must have the tumor histology and oncogenic mutation or genomic aberration specific to each dose expansion cohort defined below:
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SW-682SW-682 tablet administered orally | Drug | Part 2 Dose Expansion Cohort 1, Part 2 Dose Expansion Cohort 2, Part 2 Dose Expansion Cohort 3, Part 2 Dose Expansion Cohort 4, Phase 1 Dose Escalation Cohorts Ranging in Dose |
| Combination TherapyAppropriate combination therapy | Drug | Part 2 Dose Expansion Cohort 4 |
Primary outcome
Incidence of Adverse Events (Part 1 Only)
Time frame: Up to 24 months
Safety and tolerability endpoint evaluation via incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment emergent adverse events (TEAE)
Maximum Tolerated Dose (Part 1 Only)
Time frame: Up to 24 months
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.
Recommended Dose for Expansion (Part 1 Only)
Time frame: Up to 24 months
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.
Objective Response Rate (Part 2 Only)
Time frame: Up to 24 months
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.
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- US Medical Information website, Medical ResourcesLink provided by the sponsor.
- Individual participant dataSharing planned: No. IPD will not be shared for Phase I interventional or observational studies. Further information on how to request data can be found on our website bit.ly/IPD21.
Related trials for Advanced Solid Tumor
RecruitingPhase 1
A Study of DS-1103a Combination Therapy in Participants With Advanced Solid Tumors
Advanced Solid Tumor
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 1
Personalized KXV01 Lentinvivo (TCR) Injection as the Therapy for Advanced Solid Tumors
Advanced Solid Tumors
RecruitingPhase 1
A Study of LY4257496 in Participants With Cancer (OMNIRAY)
Breast Neoplasms, Colorectal Neoplasms
RecruitingPhase 1
A Study to Learn About Study Medicine ALTA3263 in Adults With Advanced Solid Tumors With KRAS Mutations
Cancer, PDAC - Pancreatic Ductal Adenocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Responsible study director
SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SW-682 and Combination Therapy in people with Advanced Solid Tumor and Mesothelioma, Malignant, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact US Medical Information (888-275-7376, eMediUSA@emdserono.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events (Part 1 Only) (time frame: Up to 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.