AG-120 + AG-881 for Brain Tumor

No longer recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Institut de Recherches Internationales Servier

Must not be taking: IDH inhibitors, Avastin

Disqualifiers: Recent chemotherapy, Recent radiation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two treatments, AG-120 (also known as Ivosidenib or Tibsovo) and AG-881, can lower a compound called 2-HG in brain tumors with an IDH-1 mutation. It targets individuals with specific brain tumors (oligodendroglioma or astrocytoma) who do not urgently need surgery. Participants will receive either AG-120, AG-881, or no treatment before surgery, with the option to continue treatment afterward. Ideal candidates have a specific tumor type with a certain genetic mutation and plan surgery in a few months. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have had any systemic anti-cancer therapy within 1 month before starting the trial drugs. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AG-120, also known as ivosidenib, is generally safe for patients with advanced brain tumors called gliomas. Patients tolerated the treatment well, and the side effects remained manageable. Previous studies also found that some patients' conditions stayed stable during the treatment.

For AG-881, also called vorasidenib, studies found it safe for patients with gliomas. Most patients experienced stable disease while on this treatment. It also effectively reduced 2-HG levels, which are linked to tumor growth.

Both treatments have shown promising safety results in earlier studies, indicating they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AG-120 and AG-881 for brain tumors because these treatments target a specific enzyme, IDH1/2, that is often mutated in these tumors. Unlike most standard treatments like surgery, radiation, or chemotherapy, which broadly attack cancer cells, AG-120 and AG-881 are designed to specifically inhibit these mutations, potentially leading to more effective and less toxic therapy. This targeted approach not only promises to directly tackle the root of the tumor growth but also offers hope for improved outcomes and reduced side effects compared to conventional treatments.

What evidence suggests that this trial's treatments could be effective for brain tumors?

Research has shown that Ivosidenib (AG-120), one of the treatments in this trial, may help treat IDH1-mutant gliomas, a type of brain tumor. It significantly slows tumor growth, reducing the growth rate from 26% to 9% over six months. Additionally, it lowers levels of 2-HG, a harmful substance in tumors, by over 90%. Vorasidenib (AG-881), another treatment option in this trial, effectively enters the brain and reduces 2-HG in tumor tissue by more than 97% in animal studies. Vorasidenib has also extended the time patients live without needing further treatment. Both treatments are under study in this trial for their potential to manage this type of brain tumor effectively. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with a confirmed diagnosis of low-grade glioma (a type of brain tumor) that has not been enhanced by previous treatments. Participants must have a specific gene mutation (IDH1 R132H), be fit for surgery but not in urgent need, and have an expected survival time of over 12 months. They should not have had radiation within the last 6 months or any prior treatment with IDH inhibitors or certain other cancer drugs.

Inclusion Criteria

I can care for myself but may need occasional assistance.

I am a candidate for surgery, but it's not urgent and can be scheduled within 2-4 months.

My cancer has a specific IDH1 mutation and I know my 1p19q and ATRX mutation status.

Exclusion Criteria

I have been treated with an IDH inhibitor before.

I haven't taken cancer drugs or experimental treatments within the last month.

I have not had radiation in the last 6 months, but I may have had a biopsy or surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AG-120 or AG-881 orally for 28 days prior to surgery

4 weeks

Continuous dosing

Surgery

Surgical resection of glioma tumors is performed

Post-Surgery Treatment (optional)

Participants have the option to continue treatment with AG-120 or AG-881

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AG-120
• AG-881

Trial Overview The study tests AG-120 and AG-881's effectiveness at reducing levels of a substance called 2-HG in tumors from patients with IDH-1 mutant gliomas. Before surgical removal, participants will receive one of these drugs to see how well it suppresses this substance in their tumor tissue.

How Is the Trial Designed?

Group I: AG-881 Experimental Treatment 1 Intervention

AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-881.

Group II: AG-120 Experimental Treatment 1 Intervention

AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 .

Group III: No Treatment Pre-Surgery Active Control 1 Intervention

Subjects will not receive treatment prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 or AG-881.

AG-120 is already approved in United States for the following indications:

Approved in United States as Tibsovo for:

• Acute myeloid leukemia (AML) with a susceptible IDH1 mutation

Who Is Running the Clinical Trial?

Institut de Recherches Internationales Servier

Lead Sponsor

Trials

91

Recruited

67,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11795303/

Ivosidenib for the treatment of IDH1-mutant glioma, grades 2–4 Ivosidenib seems to be effective in both grade 2 and 3 nonenhancing tumors. Ivosidenib was less effective in patients with enhancing disease.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.03327

Ivosidenib in Isocitrate Dehydrogenase 1–Mutated ... The estimated tumor growth rate per 6 months was 26% (95% CI, 9% to 46%) in the pretreatment period and 9% (95% CI, 1% to 20%) with ivosidenib ( ...

3. nature.com nature.com/articles/s41591-022-02141-2

Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma Tumor 2-HG concentrations were reduced by 92.6% (95% credible interval (CrI), 76.1–97.6) and 91.1% (95% CrI, 72.0–97.0) in patients treated with ...

4. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-presents-new-pharmacodynamic-and-response-data-both

Press Release Details Preliminary Efficacy Data Show 31% Overall Response Rate for Both Vorasidenib and TIBSOVO® with Postoperative Treatment –.

5. onclive.com onclive.com/view/perioperative-vorasidenib-and-ivosidenib-remain-effective-safe-in-idh1-diffuse-glioma

Perioperative Vorasidenib and Ivosidenib Remain ... Perioperative vorasidenib or ivosidenib demonstrated sustained clinical benefit in patients with predominantly non-enhancing IDH1-mutant diffuse glioma.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32530764/

Ivosidenib in Isocitrate Dehydrogenase 1 - Mutated Advanced ... In patients with mIDH1 advanced glioma, ivosidenib 500 mg once per day was associated with a favorable safety profile, prolonged disease ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2040

Retrospective study of ivosidenib for patients with recurrent ... Treatment with Ivosidenib therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre- ...

8. academic.oup.com academic.oup.com/noa/article/7/1/vdae227/7928930

Ivosidenib for the treatment of IDH1-mutant glioma, grades 2–4 We retrospectively reviewed clinical and radiographic data from patients with IDHm glioma treated with ivosidenib monotherapy from 2020 to 2024 ...

9. pubs.acs.org pubs.acs.org/doi/10.1021/acsmedchemlett.7b00421

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant ... Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumors in patients with inborn errors of 2HG metab.