Clinical Research Directory

Inclusion Criteria: 1. Currently active on VS-6766-201(RAMP-201) study while receiving avutometinib in combination with defactinib, have not required prior permanent discontinuation of avutometinib plus defactinib. Any active dose hold from the RAMP-201 study should be ≤ 28 days at the time of Screening for the OLE study. 2. Investigator assessment that the participant is deriving clinical benefit from study treatment (e.g., complete response, partial response, or stable disease), as determined by the investigator. 3. Female participants of childbearing potential must agree to use a highly effective method of contraception throughout OLE study participation and for at least 30 days after the last dose of study treatment. Note: Female participants of childbearing potential must have a negative serum or urine pregnancy test at Screening/Eligibility prior to the first OLE dose. 4. Ability and willingness to provide written informed consent for participation in the study and for continued data collection. Exclusion Criteria: 1. Radiographic or clinical disease progression or discontinuation of treatment for any reason during the VS-6766-201 (RAMP-201) study or at the time of screening in this study. 2. Participants on an active dose hold in the VS-6766-201 (RAMP-201) study may transition to this study only after the underlying issue has been clinically resolved and the investigator, in consultation with the Sponsor, confirms that continued treatment is appropriate. 3. Receipt of new systemic anti-cancer therapy since participation in the RAMP-201 study. 4. Participation in another interventional clinical study or receipt of other investigational therapy since participation in VS-6766-201 (RAMP-201) study. 5. Any active or uncontrolled medical condition that, in the investigator's judgment, would pose unacceptable risk or interfere with continued treatment, including but not limited to severe cardiac, pulmonary, neurologic, dermatologic, gastrointestinal, hepatic, or active infectious disease. 6. Any active or history of clinically significant ocular disorder that may increase the risk of MEK-inhibitor-related ocular toxicity (e.g., retinal vein occlusion, serous retinopathy, retinal detachment, or clinically significant macular pathology). 7. Concomitant use of medications known to have clinically significant interactions with avutometinib or defactinib that cannot be safely discontinued or substituted prior to study dosing (e.g., strong CYP3A4 inducers or inhibitors, warfarin). 8. Positive pregnancy test at Screening, breastfeeding, or unwillingness to use adequate contraception during the study. 9. Any condition or circumstance that, in the investigator's opinion, may compromise participant safety, compliance or continued benefit from study treatment.