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

Study Overview
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Brief Summary
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RSC-101 is a Phase 1a/1b clinical trial of RSC-1255 in adult study participants with advanced solid tumor malignancies who are intolerant of existing therapies known to provide clinical benefit, have disease that has progressed after standard therapy, or have previously failed other therapies. The study has two phases. The purpose of Phase 1a (Dose Escalation) is to confirm the appropriate treatment dose and Phase 1b (Dose Expansion) is to characterize the safety and efficacy of RSC-1255.

Detailed Description
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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.

Official Title
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A Phase Ia/Ib, Open Label, Multi-center, Non-randomized Dose Escalation and Dose Expansion Study of RSC-1255 in Patients With Advanced Solid Tumor Malignancies

Conditions
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Advanced Malignant Solid Neoplasm, RAS Mutation, Lung Cancer, Colon Cancer, Glioblastoma, Pancreatic Cancer

Intervention / Treatment
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* Drug: RSC-1255 Dose Escalation
* Drug: RSC-1255 Dose Expansion


Participation Criteria
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Eligibility Criteria
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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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RSC-1255 Treatment<br>Single Arm Study. All study participants receive RSC-1255. | Drug: RSC-1255 Dose Escalation<br>* Phase 1a will enroll 24-34 participants to identify the dose limiting toxicity (DLT), recommended Phase 1b dose, and the safety and tolerability of RSC-1255. RSC-1255 is administered orally twice daily, without food. Each cycle is 21 days.<br>* Other names: Dose Escalation;Drug: RSC-1255 Dose Expansion<br>* Phase 1b will enroll 48-104 participants to further characterize the safety, pharmacology, and clinical efficacy of RSC-1255. RSC-1255 is administered orally twice daily, without food. Each cycle is 21 days.<br>* Other names: Dose Expansion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) for RSC-1255 as monotherapy | The number and type of dose-limiting toxicities (DLTs) as defined in the protocol that occur during the first 28 days of treatment and all maximum grade of all maximum grade of all treatment-related events using CTCAE V5.0 will be used to identify a safe and tolerable dose. | Approximately 12 months | 
| Recommended Phase 2 Dose (RP2D) for RSC-1255 as monotherapy | The number and type of DLTs as defined in the protocol that occur during the first 28 days of treatment and all maximum grade of all treatment-related adverse events using CTCAE 5.0 will be used to identify a safe and tolerable dose. | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event profile of RSC-1255 | Toxicities will be graded according to CTCAE V5.0. | Approximately 24 months | 
| Overall Survival (OS) | Overall Survival will be assessed using RECIST V1.1. | Approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignancy, Refractory, RAS mutation, Lung, Colon, Glioblastoma, RSC-1255, Progression, Pancreatic, Cancer