Dose Escalation of RMC-5552 Monotherapy in Relapsed/Refractory Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-5552 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).

Detailed Description
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This is an open-label, multicenter, Phase 1/1b study of RMC-5552 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the mTOR pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Official Title
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A Phase 1/1b, Open-Label, Multicenter, Dose-Escalation Study of RMC 5552 Monotherapy in Adult Subjects With Relapsed/Refractory Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: RMC-5552


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants (male or female) ≥18 years of age Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Participants in the Dose-Expansion Component must have molecular aberrations in the mTOR pathway Adequate hematologic, hepatic and renal function Exclusion Criteria: Known or suspected leptomeningeal or brain metastases or spinal cord compression Primary central nervous system (CNS) tumors Clinically significant cardiac disease Active, clinically significant interstitial lung disease or pneumonitis Subjects with abnormal fasting glucose, type 1 diabetes, or uncontrolled type 2 diabetes are excluded. Subjects with stomatitis or mucositis of any grade

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RMC-5552<br>RMC-5552 for IV administration | Drug: RMC-5552<br>* RMC-5552 for IV administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values or vital signs for RMC-5552 monotherapy | up to 3 years | 
| Number of participants with dose limiting toxicities (DLTs) | Incidence and nature of DLTs with RMC-5552 monotherapy | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Peak plasma concentration of RMC-5552 | up to 3 years | 
| Tmax | Time to achieve peak plasma concentration of RMC-5552 | up to 3 years | 
| Area Under the Curve (AUC) | Area under the plasma concentration time curve of RMC-5552 | up to 3 years | 
| t1/2 | Elimination half-life of RMC-5552 | up to 3 years | 
| Accumulation Ratio | Ratio of accumulation of RMC-5552 from a single dose to steady state with repeated dosing | up to 3 years | 
| Overall Response Rate (ORR) | Overall response rate of RMC-5552 per RECIST v1.1 | up to 3 years | 
| Duration of Response (DOR) | Duration of response of RMC-5552 per RECIST v1.1 | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MYC, PIK3CA, PTEN, TSC1/2, STK11, MTOR, MAPK, advanced solid tumor, advanced solid malignancies, melanoma, skin cancer, ovarian cancer, endometrium/uterus cancer, bladder cancer, cervical cancer, Carcinoma, Non-Small-Cell Lung, Neoplasms, Squamous Cell, Carcinoma, Squamous Cell, Esophageal Neoplasms, Carcinoma, Bronchogenic, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Diseases, Neoplasms, Glandular and Epithelial, Gastrointestinal Neoplasms, Digestive System Neoplasms, Head and Neck Neoplasms, Digestive System Diseases, Esophageal Diseases, Gastrointestinal Diseases, 4EBP1