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

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

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).

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: RMC-5552

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92868
      • UC Irvine - Chao Family Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94115
      • UC San Francisco - Helen Diller Family Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma - Stephenson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - Tennessee Oncology, PLLC
  • Texas
    • Austin, Texas, United States, 78712
      • Dell Seton Medical Center at University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RMC-5552; RMC-5552 for IV administration	Drug: RMC-5552; RMC-5552 for IV administration

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Revolution Medicines, Inc.
• Investigators: Study Director: Revolution Medicines, Inc, Revolution Medicines, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Actual): May 6, 2024
• Study Completion (Actual): June 28, 2024

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Neoplasms; Gastrointestinal Diseases; Digestive System Diseases; bladder cancer; ovarian cancer; Lung Diseases; PIK3CA; melanoma; Carcinoma, Non-Small-Cell Lung; advanced solid tumor; MAPK; Esophageal Diseases; Thoracic Neoplasms; cervical cancer; Head and Neck Neoplasms; Bronchial Neoplasms; Neoplasms, Glandular and Epithelial; skin cancer; Esophageal Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; PTEN; Lung Neoplasms; Carcinoma, Bronchogenic; TSC1/2; STK11; MTOR; MYC; advanced solid malignancies; endometrium/uterus cancer; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Respiratory Tract Neoplasms; 4EBP1
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: RMC-5552-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No