Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas
- Registration Number
- NCT05130866
- Lead Sponsor
- Recursion Pharmaceuticals Inc.
- Brief Summary
This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas.
- Detailed Description
Cohort A (Phase 2) will provide early data on efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas, and provide guidance for the dose in the confirmatory part of the study (Cohort B, Phase 3). The purpose of Cohort B of the study is to assess the efficacy and safety of REC-2282 compared with placebo in participants with progressive NF2 mutated meningiomas.
In both cohorts, there will be a screening period of up to 8 weeks, a treatment period, a 4-week safety follow-up period after the end of treatment, and a 6-month post-study follow-up. The first 8 participants enrolled in Cohort A will complete a food effect run-in sub study. At the end of the study period, participants may be offered participation in an open-label extension (OLE) period.
In Cohort A, adult participants will be randomized to one of two dose levels of REC-2282.
In Cohort B, participants will be randomized to REC-2282 treatment (dose to be determined from Cohort A) arm or placebo arm in a ratio of 2:1.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
- ≥12 years of age and weighing at least 40 kg
- Progressive meningioma that is amenable to volumetric analysis
- Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
- Adequate bone marrow function
- Has provided written informed consent/assent to participate in the study
- Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
- Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 12 months prior to screening.
- Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
- History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
- Received another investigational drug within 30 days prior to screening
- Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dosing cycle.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A Adults, REC-2282 40 mg REC-2282 Adult participants will receive REC-2282. Cohort B REC-2282 REC-2282 Participants will receive REC-2282. Cohort A Adults, REC-2282 60 mg REC-2282 Adult participants will receive REC-2282. Cohort A Adolescents, REC-2282 REC-2282 Adolescent participants will receive REC-2282. Cohort B Placebo Placebo Participants will receive placebo.
- Primary Outcome Measures
Name Time Method Cohort A: Number of Participants with Progression-free survival (PFS) at 6 Months 6 months In Cohort A, PFS is defined as the number of participants who are alive and progression-free at 6 months with progression defined as having an increase of 20% or more in the target tumor identified.
Cohort B: Number of Participants with PFS up to 3 years Up to 3 years In Cohort B, PFS is defined as the time from the date of randomization until disease progression or death from any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Cohort A: Number of Participants with PFS at 12 and 24 Months 12 and 24 Months In Cohort A, PFS is defined as the number of participants who are alive and progression-free at 12 and 24 months with progression defined as having an increase of 20% or more in the target tumor identified.
Cohort A: Change from Baseline in Target Tumor Volume at 6 Months 6 months Cohorts A and B: Objective Response Rate (ORR) Up to 3 years Cohorts A and B: Disease Control Rate (DCR) Up to 3 years Cohorts A and B: Time to Response (TTR) Up to 3 years Cohorts A and B: Duration of Response (DOR) Up to 3 years Cohorts A and B: Time to Surgery/radiation for Target Tumors Up to 3 years Cohorts A and B: Maximum Observed Plasma Concentration (Cmax) of REC-2282 Up to 3 years Cohorts A and B: Time to Maximum Plasma Concentration (Tmax) of REC-2282 Up to 3 years Cohorts A and B: Area under the curve from 0 to 24hr (AUC) of REC-2282 Predose to 24 hours postdose
Trial Locations
- Locations (14)
House Institute
🇺🇸Los Angeles, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Children's National Hospital
🇺🇸Washington D.C., District of Columbia, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Sarah Cannon Cancer Institute - HCA Midwest
🇺🇸Overland Park, Kansas, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University of Minnesota / Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Scroll for more (4 remaining)House Institute🇺🇸Los Angeles, California, United StatesBen HeifetzContactbheifetz@hifla.orgWilliam Slattery, MDPrincipal Investigator