REC-2282 for Meningioma

(POPLAR-NF2 Trial)

Recruiting at 13 trial locations

Overseen By Recursion Pharmaceuticals

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Recursion Pharmaceuticals Inc.

Must not be taking: Anti-tumor agents, Investigational drugs

Disqualifiers: Active malignancy, Pregnancy, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called REC-2282 to see if it can help treat specific brain tumors in patients who haven't responded to other treatments. The study will check if the drug can slow down or stop the growth of these tumors.

Will I have to stop taking my current medications?

The trial requires that you have not taken an anti-tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), before screening. It does not specify about other medications, so you should discuss your current medications with the study team.

What data supports the effectiveness of the drug REC-2282 for treating meningioma?

Research suggests that targeting epigenetic mechanisms, like using histone deacetylase inhibitors (HDACi), can be effective in treating meningiomas. In a study, HDAC inhibitors significantly reduced cell viability in most meningioma tumors tested, indicating potential effectiveness for drugs like REC-2282, which may have similar mechanisms. ^{1 2 3 4 5}

What makes the drug REC-2282 unique for treating meningioma?

REC-2282, also known as AR-42, is a novel treatment option for meningioma that may offer a new approach compared to traditional methods like surgery and radiotherapy. It is part of ongoing research to find effective medical treatments for meningiomas, especially for cases where surgery and radiotherapy are not viable or have failed. ^{1 4 6 7 8}

Eligibility Criteria

This trial is for individuals aged 12 or older, weighing at least 40 kg, with progressive meningiomas linked to NF2 mutations. Participants must have adequate bone marrow function and provide consent. It's not for those likely needing surgery soon, who've had recent tumor treatments or other clinical trials drugs, are pregnant or planning pregnancy within 90 days post-trial.

Inclusion Criteria

I am 12 years or older and weigh at least 40 kg.

My bone marrow is working well.

I have a confirmed NF2 mutation or diagnosis.

Exclusion Criteria

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

Received another investigational drug within 30 days prior to screening

I haven't had any cancer except for cured localized ones in the past 3 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 8 weeks

Treatment

Participants receive REC-2282 or placebo, with dose determined from Cohort A for Cohort B

6 months

Safety Follow-up

Participants are monitored for safety after the end of treatment

4 weeks

Post-study Follow-up

Participants are monitored for progression-free survival and other outcomes

6 months

Open-label Extension (optional)

Participants may opt into continuation of treatment long-term

Treatment Details

Interventions

• Placebo (Placebo)
• REC-2282 (Unknown)

Trial Overview The study compares the effectiveness and safety of a new medication called REC-2282 against a placebo in patients with NF2 mutated meningiomas. The trial randomly assigns participants to either group and measures how well the tumors respond to treatment.

Participant Groups

Group I: Cohort B Active Experimental Treatment 1 Intervention

Dose TBD

Group II: Cohort A Adults, Dose 60 mg Experimental Treatment 1 Intervention

Group III: Cohort A Adults, Dose 40 mg Experimental Treatment 1 Intervention

Group IV: Cohort A Adolescents Experimental Treatment 1 Intervention

Starting dose of 30 mg followed by dose escalation to 40 mg and 60 mg.

Group V: Cohort B Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Recursion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

450+

Findings from Research

In a study of 25 patients with nonresectable meningioma on long-term mifepristone therapy, fatigue was the most common side effect, affecting 22 patients, indicating a need for monitoring patient well-being during treatment.

While mifepristone can be safely administered for extended periods, regular ultrasound and thyroid function tests are recommended to monitor for potential complications like endometrial thickening and hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of patients receiving long-term treatment with mifepristone. Spitz, IM., Grunberg, SM., Chabbert-Buffet, N., et al.[2022]

In a study of 43 meningioma tumors, histone deacetylase inhibitors (HDACi), particularly panobinostat, were found to significantly reduce cell viability in 36 tumors, indicating strong potential for epigenetic therapies in treating these tumors.

The research suggests that targeting epigenetic mechanisms, such as G9a and Jumonji-domain inhibition, could be effective for meningiomas, especially as sensitivity to these treatments increased with tumor grade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies. Tatman, PD., Wroblewski, TH., Fringuello, AR., et al.[2023]

The treatment for patients with subtotally resected or recurrent meningiomas, especially WHO grade II and III tumors, is not well established, highlighting a significant gap in high-quality evidence for effective interventions.

There is a pressing need for high-quality, multicenter clinical trials to explore optimal treatment strategies for these patients, as current therapies show minimal impact on survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opportunities for clinical research in meningioma. Vogelbaum, MA., Leland Rogers, C., Linskey, MA., et al.[2021]

Recent literature highlights the exploration of new chemotherapeutic options for treating progressive and atypical meningiomas, indicating a growing interest in developing effective treatments for these challenging tumors.

Combination therapies targeting multiple molecular pathways show promise as potential adjuvant treatments, but further molecular studies are needed to better understand meningioma biology and identify specific therapeutic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative Therapeutic Strategies in the Treatment of Meningioma. Caruso, G., Elbabaa, SK., Gonzalez-Lopez, P., et al.[2015]

In a study of 164 patients with recurrent grade 1 and 2 meningiomas, loss of H3K27me3 expression was found in 83 patients and was significantly associated with a higher risk of earlier re-recurrence, indicating its potential as a prognostic marker.

The study demonstrated that loss of H3K27me3 is an independent factor predicting shorter progression-free survival (PFS) in recurrent grade 1 meningiomas, suggesting that H3K27me3 testing could be beneficial in clinical settings for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loss of H3K27me3 expression enriches in recurrent grade 1&2 meningiomas and maintains as a biomarker stratifying progression risk. Hua, L., Ren, L., Wu, Q., et al.[2023]

Stereotactic radiosurgery (SRS) significantly improves tumor control in patients with incidental meningiomas compared to observation, with a mean follow-up of over 3 years showing a very low tumor progression rate (pooled OR: 0.06).

Certain risk factors, including MRI T2 hyperintensity and larger initial tumor diameter, are associated with higher rates of tumor progression, suggesting that these factors can help predict which tumors may grow more rapidly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery Versus Observation for Treating Incidental Meningiomas: A Systematic Review and Meta-Analysis. Zhang, C., Zhang, H.[2021]

In a review of 48 phase II clinical trials for meningioma, the most commonly used primary efficacy endpoint was progression-free survival (PFS), utilized in 38% of the trials, highlighting its importance in evaluating treatment effectiveness.

The study suggests that using multiple efficacy endpoints, particularly time-to-event measures, may be more appropriate for assessing outcomes in meningioma trials due to the complexity of the disease and variability in lesion characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy Endpoints in Phase II Clinical Trials for Meningioma: An Analysis of Recent Clinical Trials. Watanabe, S., Nonaka, T., Maeda, M., et al.[2023]

Meningiomas are mostly benign tumors, and complete surgical resection is typically curative, making surgery the preferred treatment for symptomatic patients.

For patients with unresectable or recurrent meningiomas, stereotactic radiotherapy (SRT) is increasingly used as a less invasive alternative, especially for those at high surgical risk or with tumors in difficult locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meningiomas. Chamberlain, MC.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Management of patients receiving long-term treatment with mifepristone. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Opportunities for clinical research in meningioma. [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Innovative Therapeutic Strategies in the Treatment of Meningioma. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Loss of H3K27me3 expression enriches in recurrent grade 1&2 meningiomas and maintains as a biomarker stratifying progression risk. [2023]

6. Turkey pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery Versus Observation for Treating Incidental Meningiomas: A Systematic Review and Meta-Analysis. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy Endpoints in Phase II Clinical Trials for Meningioma: An Analysis of Recent Clinical Trials. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Meningiomas. [2020]