Nivolumab for Recurrent or Progressive IDH Mutant Gliomas

NCT03557359 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAR6354
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

The objective of this study is to determine response rates (partial and complete responses) to nivolumab of recurrent or progressive IDH mutant (grades 2, 3 or 4) gliomas with prior exposure to alkylating agents.

Conditions

Gliomas

Keywords

Recurrent; Progressive; High Grade Glioma; IDH Mutant; Low Grade Glioma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The overall response rate is defined as the percentage of patients with a reduction in tumor size while on treatment.

  Throughout treatment duration or until progressive disease, unacceptable toxicity, or withdrawal of consent, up to 2 years

Secondary Outcomes (3)

• Duration of Response

  Until the first date that progressive disease is objectively documented or until study completion (36 months)

• Progression-Free Survival (PFS)

  Until death or study completion (36 months)

• Overall Survival (OS)

  Until death or study completion (36 months)

Study Arms (1)

Nivolumab

EXPERIMENTAL

Nivolumab 240 mg will be given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg will be given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab will be administered as a 30-minute infusion. A finite treatment duration with immune therapies in this participant population remains an area of ongoing research; therefore the treatment duration chosen was 2 years.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab (Opdivo®) is a human monoclonal antibody (HuMAb; immunoglobulin G4 (IgG4)- S228P) that targets the PD-1 cluster of differentiation 279 (CD279) cell surface membrane receptor.

Also known as: Opdivo®

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
• Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
• Participant must be 18 years of age or older
• Participants with pathologically confirmed grade 2, 3 or 4 gliomas with IDH mutation (confirmed by IDH R132H immunohistochemistry or IDH1/IDH2 next generation sequencing) who have progressive tumor and have had previous exposure to alkylating agents.
• Participants must have measurable disease, defined as at least one enhancing tumor lesion that can be accurately measured in at least one dimension as ≥ 10mm x 10mm on brain MRI. See 13.2 Disease Parameters for more information regarding evaluation of measurable disease. Patients with non-enhancing measureable disease may be eligible upon discussion with and approval by the CUMC PI.
• Availability of baseline frozen tumor or formalin-fixed paraffin-embedded (FFPE) tumor block.
• Karnofsky Performance Score (KPS) of 60 and above
• Adequate bone marrow, kidney and liver function as defined below:
• i) White blood count (WBC) ≥ 3000/microliter (uL) ii) Neutrophils ≥ 1500/uL iii) Absolute lymphocyte count ≥ 500/uL iv) Platelets ≥ 100x103 /uL v) Hemoglobin ≥ 9.0g/dL vi) Serum creatinine ≤ 1.5x upper limit of normal (ULN) or calculated creatinine clearance (CrCl)\> 50 mL/min (using the Cockcroft-Gault formula)
• Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
• Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL vi) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN vii) Total bilirubin (TBILI) ≤ 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of \< 3.0xULN)
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug
• Women must not be pregnant or breastfeeding
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment (i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives.)
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment (i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five halflives.)

You may not qualify if:

• Participants with an active, known, or suspected autoimmune disease.
• Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Dose of dexamethasone ≤ 4 mg/day or equivalent is allowed at the study entry for brain tumor edema
• Participants who have received chemotherapy or experimental agents within 4 weeks (except for 6 weeks for nitrosoureas and 23 days for temozolomide) and radiotherapy within 12 weeks of the first dose of the study treatment.
• Prior use of PD-1, PD-L1, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors or exposure to other checkpoint inhibitors.
• Prior exposure to bevacizumab or other vascular endothelial growth factor (VEGF) or VEGFR inhibitors.
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
• History of severe allergy or hypersensitivity to nivolumab components

Sponsors & Collaborators

• Fabio Iwamoto, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Miami Cancer Center

Miami, Florida, 33176, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (10)

• Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765-73. doi: 10.1056/NEJMoa0808710.

  PMID: 19228619 BACKGROUND

• Kirkpatrick JP, Sampson JH. Recurrent malignant gliomas. Semin Radiat Oncol. 2014 Oct;24(4):289-98. doi: 10.1016/j.semradonc.2014.06.006.

  PMID: 25219814 BACKGROUND

• Burris H MI, Maher E, et al. Abstract PL04-05: The first reported results of AG-120, a first-in-class, potent inhibotior of the IDH1 mutant protein, in a Phase I study of patients with advanced IDH1-mutant solid tumors, including gliomas. Molecular Cancer Therapeutics 2015;14.

  BACKGROUND

• Sampson JH OA, Vlahovic G, Sahebjam S, Baehring J, Hafler D, Voloschin A, Latek R, Cloughesy T, Lim M, Reardon D. Safety and Activity of Nivolumab +/- Ipilimumab in Recurrent Glioblastoma: Updated Results from CHECKMATE-143. Journal of Neurosurgery 2016;124:A1189-A90.

  BACKGROUND

• Campesato LF, Barroso-Sousa R, Jimenez L, Correa BR, Sabbaga J, Hoff PM, Reis LF, Galante PA, Camargo AA. Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice. Oncotarget. 2015 Oct 27;6(33):34221-7. doi: 10.18632/oncotarget.5950.

  PMID: 26439694 BACKGROUND

• Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014 Dec 4;371(23):2189-2199. doi: 10.1056/NEJMoa1406498. Epub 2014 Nov 19.

  PMID: 25409260 BACKGROUND

• Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4.

  PMID: 26952546 BACKGROUND

• Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015 Apr 3;348(6230):124-8. doi: 10.1126/science.aaa1348. Epub 2015 Mar 12.

  PMID: 25765070 BACKGROUND

• LeBlanc VG, Marra MA. Next-Generation Sequencing Approaches in Cancer: Where Have They Brought Us and Where Will They Take Us? Cancers (Basel). 2015 Sep 23;7(3):1925-58. doi: 10.3390/cancers7030869.

  PMID: 26404381 BACKGROUND

• Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN. Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res. 2007 Apr 1;13(7):2038-45. doi: 10.1158/1078-0432.CCR-06-2149.

  PMID: 17404084 BACKGROUND

MeSH Terms

Conditions

Glioma; Recurrence

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Fabio Iwamoto
• Organization: Columbia University

fi2146@cumc.columbia.edu

212-342-0571

Study Officials

• Fabio Iwamoto, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurology at the Columbia University Medical Center

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: June 15, 2018
• Study Start: June 12, 2018
• Primary Completion: September 20, 2022
• Study Completion: February 11, 2025
• Last Updated: November 3, 2025
• Results First Posted: November 3, 2025

Record last verified: 2025-10

Locations

US (4)