NCT05345002

All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma

A Phase 2 Trial of All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: Stephen Bagley, MD, MSCE · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase II study of the combination of All-Trans Retinonic Acid (ATRA) and PD-1 inhibition (Retifanlimab) in patient with recurrent IDH-mutant glioma. The Sponsor-Investigator hypothesizes that the proposed regimen will be safe and stimulate a robust anti-tumor immune response.

Detailed description

The study has a Safety Run-In, a Phase 2 Portion, and a Surgical Portion. The Phase 2 portion and Surgical portion will open to enrollment simultaneously following successful completion of the Safety Run-In. Safety Run-In subjects receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1-14 and retifanlimab 500mg IV on day 1. Once Safety Run-In is complete, the Phase 2 and Surgical cohorts will commence uninterrupted. Phase 2: All Phase 2 patients will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1 through 14 and retifanlimab 500mg IV on day 1. Arm A includes alkylator-refractory patients at high risk for progression of disease, having failed temozolomide and another alkylating agent. At the first stage, 12 subjects will be enrolled onto the study. This arm of the trial will be stopped if no response was obtained among the first 12 subjects (0/12). Otherwise, this arm of the study will continue to stage Four additional subjects will be enrolled on the second stage of this arm of the trial. Arm B includes patients who have failed only one prior alkylating chemotherapy regimen and have gone at least 12 months since the last treatment (chemotherapy or radiation therapy), i.e., favorable risk patients. At the first stage, 14 subjects will be enrolled onto the study. This arm of the trial will be stopped if 5 or fewer responses were obtained among the first 14 subjects greater than or equal to 5 out of 14 subjects. Otherwise, this arm of the study will continue to stage 2. Three additional subjects will be enrolled on the second stage of this arm of the trial. Surgical Portion: This portion of the study will enroll patients who are eligible for re-resection at the time of recurrence. Prior to surgical resection, patients are randomized 1:1 to receive either 1) single-agent ATRA 45mg/m2/day orally in two equally divided doses for 14 days pre-surgery (Arm C), or 2) the combination of ATRA 45mg/m2/day orally in two equally divided doses for 14 days pre-surgery plus a 500mg IV dose of retifanlimab 14 (+/-3) days prior to the date of surgery (Arm D). At surgery fresh tumor tissue will be collected for correlative studies. Following surgery all patients will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1-14 and retifanlimab 500mg IV on day 1.

Conditions

• Glioma
• IDH Mutation
• Astrocytoma
• Oligodendroglioma

Interventions

Type	Name	Description
DRUG	Retifanlimab	Administered 500mg IV on day 1 of every 28-day cycle, continued until disease progression, unacceptable toxicity, or 2 years from the first dose of study medication, whichever occurs first.
DRUG	All-trans retinoic acid	All-trans retinoic acid (ATRA) 45mg/m2 orally in two equally divided doses on days 1-14 of each 28-day cycle, continued until disease progression, unacceptable toxicity, or 2 years from the first dose of study medication, whichever occurs first.

Timeline

• Start date: 2022-11-16
• Primary completion: 2027-06-01
• Completion: 2028-06-01
• First posted: 2022-04-25
• Last updated: 2026-02-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study