Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas

Neurofibromatosis Type 2 Clinical Trial

— POPLAR-NF2  

Official title:

A Two-staged, Phase 2/3, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of REC-2282 in Participants With Progressive NF2 Mutated Meningiomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05130866
• Other study ID #: REC-2282-201
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 20, 2022
• Est. completion date: July 2027

Study information

• Verified date: February 2024
• Source: Recursion Pharmaceuticals Inc.
• Contact: Recursion Pharmaceuticals
• Phone: 385-374-1724
• Email: clinicaltrials[@]recursionpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas.

Description:

This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas, with either NF2 disease-related meningioma or recurrent sporadic meningiomas that have NF2 mutations.

Cohort A 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). 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 information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: July 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. =12 years of age and weighing at least 40 kg

2. Progressive meningioma that is amenable to volumetric analysis

3. 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)

4. Adequate bone marrow function

5. Has provided written informed consent/assent to participate in the study

Exclusion Criteria:

1. Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.

2. Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening.

3. Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.

4. 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.

5. Received another investigational drug within 30 days prior to screening

6. Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.

Related Conditions & MeSH terms

• Meningioma
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis 2
• Neurofibromatosis Type 2

Intervention

Drug:
• REC-2282
Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.
• Placebo
Participants will receive placebo orally 3 times per week for 3 weeks followed by 1 week off for a 4-week cycle.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	House Institute	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Minnesota / Masonic Cancer Center	Minneapolis	Minnesota
United States	Columbia University	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Sarah Cannon Cancer Institute - HCA Midwest	Overland Park	Kansas
United States	Mayo Clinic	Rochester	Minnesota
United States	Children's National Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Recursion Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) in Cohort A	The proportion of participants in Cohort A who are alive and progression-free after 6 cycles of treatment	6 months
Primary	Progression-free survival (PFS) in Cohort B	In Cohort B, the time from the date of randomization until disease progression or death from any cause, whichever occurs first.	Time from the date of randomization until disease progression or death from any cause, whichever occurs first, assessed up to 24 months.