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

Phase 1
Completed
Conditions
Solid Tumors
Interventions
Registration Number
NCT04774952
Lead Sponsor
Revolution Medicines, Inc.
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
58
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
RMC-5552RMC-5552RMC-5552 for IV administration
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events (AEs)up to 3 years

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

Number of participants with dose limiting toxicities (DLTs)21 days

Incidence and nature of DLTs with RMC-5552 monotherapy

Secondary Outcome Measures
NameTimeMethod
Cmaxup to 3 years

Peak plasma concentration of RMC-5552

Tmaxup to 3 years

Time to achieve peak plasma concentration of RMC-5552

Area Under the Curve (AUC)up to 3 years

Area under the plasma concentration time curve of RMC-5552

Overall Response Rate (ORR)up to 3 years

Overall response rate of RMC-5552 per RECIST v1.1

Duration of Response (DOR)up to 3 years

Duration of response of RMC-5552 per RECIST v1.1

t1/2up to 3 years

Elimination half-life of RMC-5552

Accumulation Ratioup to 3 years

Ratio of accumulation of RMC-5552 from a single dose to steady state with repeated dosing

Trial Locations

Locations (8)

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Sarah Cannon Research Institute - Tennessee Oncology, PLLC

🇺🇸

Nashville, Tennessee, United States

UC Irvine - Chao Family Comprehensive Cancer Center

🇺🇸

Irvine, California, United States

UC Davis Comprehensive Cancer Center

🇺🇸

Sacramento, California, United States

UC San Francisco - Helen Diller Family Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

University of Oklahoma - Stephenson Cancer Center

🇺🇸

Oklahoma City, Oklahoma, United States

Dell Seton Medical Center at University of Texas

🇺🇸

Austin, Texas, United States

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