Ivosidenib (AG-120) With Nivolumab in IDH1 Mutant Tumors

NCT04056910 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 19-096
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, response to treatment and (progression free and overall) survival will be described and safety events of ivosidenib in combination with nivolumab will be summarized in patients with advanced solid tumors (nonresectable or metastatic) or enhancing gliomas.

Conditions

Advanced Solid Tumor; IDH1 Mutation; Glioma

Outcome Measures

Primary Outcomes (2)

• Best Overall Response

  Number of patients with Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm, Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters or Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters per RECIST v1.1 Criteria, or, per RANO Criteria: Complete Response (CR): Observed in consecutive assessments ≥4 weeks apart per RANO. Partial Response (PR): Observed in consecutive assessments ≥4 weeks apart per RANO.

  At 8 weeks after first treatment; up to 14 months for cohort

• Six Month Progression-Free Survival (PFS6)

  Percentage of participants surviving without objective tumor progression at six months after the initiation of treatment. Per RECIST v1.1 Criteria: Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression. Per RANO Criteria: Progressive Disease: No CR, PR, SD prior to PD. Progression: 25% or more increase in enhancing lesions despite stable or increasing steroid dose, increase (significant) in non-enhancing FLAIR/T2W lesions, not attributable to other non-tumor causes, any new lesions; clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease)

  At 6 months

Secondary Outcomes (3)

• Occurrence of Dose Limiting Toxicity (DLT)

  Up to 24 months

• Adverse Events Related to Treatment

  Up to 24 months

• Progression Free Survival (PFS)

  Up to 25 months

Study Arms (1)

Concurrent dosing of ivosidenib and nivolumab

EXPERIMENTAL

Ivosidenib will be administered concurrently with nivolumab on a Q28 day schedule.

Drug: ivosidenib and nivolumab

Interventions

ivosidenib and nivolumab DRUG

Ivosidenib will be administered orally at a dose of 500 mg (provided as 250 mg strength tablets) daily. The dose may be reduced to 250 mg for patients experiencing more than one event of Grade 2 nausea or vomiting (related or unrelated), or Grade 3 or Grade 4 adverse events. Nivolumab will be administered at 480 mg IV every 28 days.

Concurrent dosing of ivosidenib and nivolumab

Eligibility Criteria

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

You may qualify if:

• Be ≥18 years of age.
• Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably collected within the last 3 years) of an advanced solid tumor for which curative treatment is not available and have undergone appropriate standard of care treatment options (in the opinion of the treating investigator).
• Have a documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available) based on CLIA certified sequencing (R132C/L/G/H/S mutation variants tested).
• For glioma, must have both 1) contrast enhancing disease and 2) WHO 2016 grade II
• Have an ECOG PS score of 0 or 1 (Appendix 11.1)
• Have at least one evaluable and measurable lesion as defined by RECIST v1.1 (solid tumors) or Response Assessment in Neuro-Oncology (RANO) Criteria (glioma).
• Have recovered from toxicities associated with prior anticancer therapy to baseline or ≤ grade 1 unless stabilized under medical management per investigator.
• Have adequate bone marrow function as evidenced by:
• Absolute neutrophil count ≥ 1,500/mm3 or 1.5 × 109/L
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm3 or 100 × 109/L
• Have adequate hepatic function as evidenced by:
• Serum total bilirubin ≤ 2 × upper limit of normal (ULN), unless considered due to Gilbert's disease
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN in the presence of liver metastases (or primary hepatic tumor) OR ≤ 2× ULN within glioma patients
• Have adequate renal function as evidenced by:

You may not qualify if:

• Received a prior IDH inhibitor.
• Received systemic anticancer therapy or an investigational agent \< 2 weeks prior to Day 1). In addition, the first dose of study treatment should not occur before a period ≥ 5 half-lives (t1/2)of the investigational agent has elapsed.
• For solid tumor patients: received radiotherapy to metastatic sites of disease \< 2 weeks prior to Day 1 and for glioma patients have received radiation within 3 months prior.
• For solid tumor patients, have underwent hepatic radiation, chemoembolization, and radiofrequency ablation \< 4 weeks prior to Day 1.
• Participants must not have a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of \> 10 mg prednisone daily or equivalent at time of first dose of study treatment.
• Participants must not have active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Participants must not have a known history of non-infectious pneumonitis that required steroids for treatment.
• Participants must not have evidence of interstitial lung disease.
• For solid tumor patients, have known symptomatic brain metastases requiring steroids. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 1 week and have radiographically stable disease for at least 1 month prior to study entry.
• Have a history of another primary cancer that is active requiring treatment, progressing or for which the treating investigator believes will make disease assessment unreliable.
• Have evidence of intracranial or intra-tumoral hemorrhage either by MRI or computed tomographic (CT) scan. Participants with resolving post-surgical changes, punctate hemorrhage, or hemosiderin are eligible.
• Underwent major surgery within 4 weeks of Day 1 or have not recovered from post-surgery toxicities.
• Are pregnant or breastfeeding.
• Are taking known strong CYP3A4 inducers or sensitive CYP3A4 substrate medications with a narrow therapeutic window (Appendix 0), unless they can be transferred to other medications within ≥5 t1/2 prior to dosing.
• Are taking P-glycoprotein (P-gp) transporter-sensitive substrate medications with a narrow therapeutic window (Appendix 0), unless they can be transferred to other medications within ≥ 5 t1/2 prior to administration of study treatment.

Sponsors & Collaborators

• Jason J. Luke, MD: lead
• Agios Pharmaceuticals, Inc.: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (2)

• Nguyen MK, Jelinek M, Singh A, Isett B, Myers ES, Mullett SJ, Eisele Y, Beumer JH, Parise RA, Urban J, Rose A, Sellitto L, Singh K, Doerfler R, Dadey RE, Kim C, Rhee JC, Davar D, Villaruz LC, Burgess M, Drappatz J, Mantica M, Goodman AE, Wang H, Singhi AD, Luke JJ, Zandberg DP, Bao R. Clinical and translational study of ivosidenib plus nivolumab in advanced solid tumors harboring IDH1 mutations. Oncologist. 2025 Nov 11;30(11):oyaf362. doi: 10.1093/oncolo/oyaf362.

  PMID: 41138165 DERIVED

• Nguyen MK, Jelinek M, Singh A, Isett B, Myers ES, Mullett SJ, Eisele Y, Beumer J, Parise R, Urban J, Rose A, Sellitto L, Singh K, Doerfler R, Dadey RE, Kim C, Rhee JC, Davar D, Villaruz LC, Burgess M, Drappatz J, Mantica M, Goodman AE, Wang H, Singhi AD, Luke JJ, Zandberg DP, Bao R. Clinical and translational study of ivosidenib plus nivolumab in advanced solid tumors harboring IDH1 mutations. medRxiv [Preprint]. 2025 Jul 21:2025.07.19.25331848. doi: 10.1101/2025.07.19.25331848.

  PMID: 40778139 DERIVED

MeSH Terms

Conditions

Glioma

Interventions

ivosidenib; 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

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: Barbara Stadterman, MPH, CCRP, Clinical Research Manager
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Jason J Luke, MD, PhD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Associate Professor of Medicine

Model Details: Concurrent dosing of ivosidenib and nivolumab.

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: August 14, 2019
• Study Start: September 20, 2021
• Primary Completion: November 13, 2023
• Study Completion: November 13, 2023
• Last Updated: February 27, 2025
• Results First Posted: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)