Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT05345002

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

Led by Stephen Bagley, MD, MSCE · Updated on 2026-02-20

55

Participants Needed

1

Research Sites

289 weeks

Total Duration

On this page

Sponsors

S

Stephen Bagley, MD, MSCE

Lead Sponsor

I

Incyte Corporation

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Prior diagnosis of astrocytoma (grade 2-4) or oligodendroglioma (grade 2-3) with progression or recurrence after at least one alkylating chemotherapy
  • Tumor confirmed to have mutation in IDH1 or IDH2 by DNA sequencing
  • Measurable disease by MRI for Safety Run-In and Phase 2 patients; surgical patients must be eligible for tumor resection
  • Failed temozolomide or another alkylator for Safety Run-In; Arm A must have failed temozolomide and another alkylator; Arm B must have failed one prior alkylator and be at least 12 months since last treatment
  • Able to undergo brain MRI with gadolinium and maintain stable or decreased corticosteroid dose before baseline MRI
  • Recovered from prior treatment toxicities for specified intervals
  • If on corticosteroids for brain edema, dose must be 2 mg dexamethasone daily or less for at least 5 days before first retifanlimab dose
  • Able to swallow oral medications
  • Age 18 years or older
  • Karnofsky performance status ≥ 60
  • Life expectancy greater than 3 months
  • Adequate organ and marrow function including specific lab thresholds
  • Women of childbearing potential must have negative pregnancy test and agree to pregnancy prevention measures; males must agree to contraception if sexually active with such women
  • Able to comply with study procedures and provide informed consent
Not Eligible

You will not qualify if you...

  • Contrast-enhancing tumor in brainstem or spinal cord
  • Diffuse leptomeningeal disease
  • Received bevacizumab within last 3 months
  • Clinically significant brain mass effect or midline shift
  • Use of immunosuppressive medications other than steroids within 6 months
  • Prior diagnosis of immunodeficiency
  • Prior solid organ or bone marrow transplant
  • Active autoimmune disease requiring systemic immunosuppression above physiologic doses
  • Interstitial lung disease, active pneumonitis, or history thereof
  • Prior severe immune-related toxicity from checkpoint inhibitors requiring discontinuation
  • Active hepatitis B or C infection
  • HIV-positive on antiretroviral therapy
  • Prior or concurrent malignancy interfering with study assessments
  • Serious uncontrolled medical disorders or infections
  • Significant cardiovascular disease including recent myocardial infarction or severe heart failure
  • Known hypersensitivity or allergy to retifanlimab, ATRA, or monoclonal antibodies
  • Prisoners or involuntarily detained individuals
  • Pregnant women
  • Received live vaccines within 28 days before study start
  • Current enrollment in other interventional clinical trials

AI-Screening

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Trial Site Locations

Total: 1 location

1

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

4

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