Solid Tumors
Conditions
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
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.
Interventions
DRUGRMC-5552
RMC-5552 for IV administration
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Tmax | up 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 |
| Duration of Response (DOR) | up to 3 years | Duration of response of RMC-5552 per RECIST v1.1 |
| Accumulation Ratio | up to 3 years | Ratio of accumulation of RMC-5552 from a single dose to steady state with repeated dosing |
| Overall Response Rate (ORR) | up to 3 years | Overall response rate of RMC-5552 per RECIST v1.1 |
| t1/2 | up to 3 years | Elimination half-life of RMC-5552 |
| Cmax | up to 3 years | Peak plasma concentration of RMC-5552 |
Countries
United States
Outcome results
None listed