Actively Recruiting
A Phase 2 Trial of 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
52 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
Researchers are evaluating the combination of All-Trans Retinoic Acid (ATRA) and PD-1 inhibitor retifanlimab in patients with recurrent IDH-mutant glioma, a type of brain tumor. This Phase II study aims to assess whether this treatment regimen is safe and can stimulate a strong anti-tumor immune response. The study includes a Safety Run-In phase, a Phase 2 portion, and a Surgical portion to explore different patient groups and treatment settings. During the Safety Run-In, patients receive 28-day treatment cycles with oral ATRA given twice daily on days 1-14 and retifanlimab given intravenously on day 1. Following this, the Phase 2 part enrolls patients in two arms based on their prior chemotherapy history, receiving the same ATRA and retifanlimab schedule. The Surgical portion enrolls patients eligible for tumor removal surgery, randomizing them to either ATRA alone or ATRA plus retifanlimab before surgery, followed by the combination treatment cycles post-surgery. Participants will undergo regular assessments including brain MRIs to measure tumor response using radiographic criteria. Researchers will monitor treatment safety, progression-free survival, and overall survival over months to years. Patients must meet specific health criteria and agree to study procedures, including taking oral medications and attending scheduled visits. The study lasts until disease progression, unacceptable side effects, or up to two years of treatment.
CONDITIONS
Brief Title
All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Histopathologically confirmed astrocytoma (grade 2-4) or oligodendroglioma (grade 2-3) with progression or recurrence after at least one prior alkylating chemotherapy
- Tumor must have a confirmed IDH1 or IDH2 mutation by DNA sequencing
- For Safety Run-In and Phase 2: measurable disease per defined MRI criteria
- Arm A: failed temozolomide and another alkylating agent
- Arm B: failed only one prior alkylating chemotherapy and at least 12 months since last treatment
- Surgical Arms (C and D): eligible for tumor resection, no measurable disease required
- Ability to undergo brain MRI with gadolinium
- Stable or decreasing corticosteroid dose before baseline MRI
- Recovered from severe toxicity of prior treatments with defined waiting periods
- Corticosteroid dose 2mg dexamethasone or less daily for at least 5 days prior to first retifanlimab dose
- Able to swallow oral medications
- Karnofsky performance status ≥ 60
- Life expectancy greater than 3 months
- Adequate organ and marrow function with specific lab value thresholds
- Women of childbearing potential must have negative pregnancy test and use contraception
- Male participants with partners of childbearing potential must agree to contraception
- Ability to comply with study procedures and provide informed consent
You will not qualify if you...
- Tumor in brainstem or spinal cord with contrast enhancement
- Diffuse leptomeningeal disease
- Use of bevacizumab within 3 months prior
- Clinically significant mass effect or midline brain shift
- Use of immunosuppressive medication other than steroids within 6 months
- Prior immunodeficiency diagnosis
- History of organ or bone marrow transplantation
- Active autoimmune disease requiring immunosuppression exceeding physiologic corticosteroid doses
- Interstitial lung disease or active pneumonitis
- Severe immune-related toxicity from prior checkpoint inhibitor therapy
- Active hepatitis B or C infection
- HIV infection on antiretroviral therapy
- Prior or concurrent malignancy interfering with study assessments
- Serious uncontrolled medical disorders or infections
- Significant cardiovascular disease including recent heart attack, arrhythmias, or severe heart failure
- Known hypersensitivity to monoclonal antibodies, retifanlimab, ATRA, or retinoids
- Prisoners or involuntarily incarcerated individuals
- Pregnant women
- Receipt of live vaccine within 28 days prior to study treatment
- Concurrent enrollment in other interventional clinical trials
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 28 days per cycle
Participants receive 28-day cycles of treatment with oral ATRA on days 1-14 and retifanlimab IV on day 1 to assess safety before proceeding to the main trial phases.
1 visit per 28-day cycle
Duration - Repeated 28-day cycles until disease progression or discontinuation
Participants receive repeated 28-day cycles of treatment with oral ATRA on days 1-14 and retifanlimab IV on day 1 until disease progression, unacceptable toxicity, or up to 2 years.
1 visit per 28-day cycle
Duration - 14 days pre-surgery
Participants eligible for surgery receive oral ATRA for 14 days before surgery, with some also receiving a single IV dose of retifanlimab approximately 14 days before surgery.
1 to 2 visits depending on surgical scheduling
Duration - Day of surgery
Participants undergo tumor resection surgery with tumor tissue collection for research purposes.
1 visit (surgery day)
Duration - Repeated 28-day cycles until disease progression or discontinuation
Following surgery, participants receive repeated 28-day cycles of treatment with oral ATRA on days 1-14 and retifanlimab IV on day 1 until disease progression, unacceptable toxicity, or up to 2 years.
1 visit per 28-day cycle
Trial Site Locations
Total: 1 location
1
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
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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