Neoplasms

All Conditions

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ivosidenib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

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

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.

ivosidenib and nivolumab

Jason J Luke, MD, PhD

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.

This study will describe the safety, response rate, progression free and overall survival, and summarize safety events of ivosidenib in combination with nivolumab in participants with advanced solid tumors (nonresectable or metastatic) or enhancing gliomas. Participants are required to have a histologically consistent diagnosis of IDH1 gene mutated tumor that is not eligible for curative therapy. Enrolled subjects will receive orally administered ivosidenib dosed daily on 28-day cycles and nivolumab will be infused every 28 days. Participants will be assessed at every visit for adverse events starting from the first dose of study treatment. Assessment (CT or MRI) for evaluation of disease response will be conducted every 8 weeks (±7 days) from the first day of treatment cycle 1 and/or at any time when progression of disease is suspected. A Post-Treatment Follow-Up Visit for safety will occur 28 (+/- 5) days after the last dose of study drug.

Concurrent dosing of ivosidenib and nivolumab.

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

Phase II Study of IDH1 Inhibitor Ivosidenib and Nivolumab in IDH1 Mutant Gliomas and Advanced Solid Tumors

RECIST v1.1 Criteria: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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

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.

Proportion of participants surviving without objective tumor progression at six months after the initiation of treatment.

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.

RANO Criteria: Progressive Disease: No CR, PR, SD prior to PD.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)

The occurrence (number) of dose limiting toxicity (DLT) in patients receiving ivosidenib plus nivolumab. DLT describes side effects of the treatment that are serious enough to prevent an increase in dose or level of that treatment.

Adverse events per NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0), experienced by patients related to their receiving the treatment combination of ivosidenib and nivolumab.

The time from first dose of either drug until disease progression or death from any cause, whichever occurs first.

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.

RANO Criteria: Progressive Disease: No CR, PR, SD prior to PD.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)

Spots Global Cancer Trial Database for ivosidenib and nivolumab