A Trial of RSC-1255 for Treatment of Patients With Advanced Malignancies

RSC-1255 is an orally bioavailable, small-molecule direct pan-mutant and wild-type RAS inhibitor. RSC-101 is a Phase 1a/1b, open-label, multi-center, non-randomized, Dose Escalation and Dose Expansion study in participants with advanced solid tumor malignancies. Study enrollment is approximately 134 participants. All participants receive oral RSC-1255, twice daily as monotherapy. Following Phase 1a (Dose Escalation) to identify the Maximum Tolerated Dose and Recommended Dose for use in Phase 1b, additional participants are enrolled in the Phase 1b (Dose Expansion) to further characterize the safety, pharmacology, and the clinical efficacy of RSC-1255 as monotherapy and in combination with the autophagy inhibitor hydroxychloroquine (HCQ).

Inclusion criteria

(Key Factors):

• Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:

• Participant is intolerant of existing therapy(ies) known to provide clinical benefit for their condition
• Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit
• Malignancy has progressed on standard therapy
• Has evaluable or measurable tumor(s) in dose-escalation by standard radiological and/or laboratory assessments as applicable to their malignancy.
• Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG).
• Is age ≥ 18 years.
• Has either tissue agnostic tumors and documented RAS mutations or with glioblastoma with or without mutation in RAS

Exclusion criteria

(Key Factors):

• Participants receiving cancer therapy at the time of enrollment.
• Any clinically significant disease or condition affecting a major organ system.
• Significant cardiovascular disease or electrocardiogram (ECG) abnormalities.
• Known Gilbert's disease.
• Has had a previous (within 2 years) or has a current malignancy other than the target cancer.
• Intermittent hypokalemia
• Grade 1 or higher nausea, vomiting, diarrhea at baseline due to underlying disease