Clinical trial NCT04774952: Dose Escalation of RMC-5552 Monotherapy in Relapsed/Refractory Solid Tumors
Official title: A Phase 1/1b, Open-Label, Multicenter, Dose-Escalation Study of RMC 5552 Monotherapy in Adult Subjects With Relapsed/Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: PIK3CA
PTEN
TSC1/2
STK11
MTOR
MYC
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
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-01
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: up to 3 years
measure: Number of participants with dose limiting toxicities (DLTs)
timeFrame: 21 days
Secondary outcomes:
measure: Cmax
timeFrame: up to 3 years
measure: Tmax
timeFrame: up to 3 years
measure: Area Under the Curve (AUC)
timeFrame: up to 3 years
measure: t1/2
timeFrame: up to 3 years
measure: Accumulation Ratio
timeFrame: up to 3 years
measure: Overall Response Rate (ORR)
timeFrame: up to 3 years
measure: Duration of Response (DOR)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Irvine
country: United States
facility: UC Irvine - Chao Family Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UC San Francisco - Helen Diller Family Comprehensive Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma - Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology, PLLC
state: Tennessee
city: Austin
country: United States
facility: Dell Seton Medical Center at University of Texas
state: Texas
Study officials:
affiliation: Revolution Medicines, Inc.
name: Revolution Medicines, Inc
role: STUDY_DIRECTOR
References: