AG-120 for Blood Cancers

Recruiting at 32 trial locations

Overseen By Institut de Recherches Internationales Servier Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Institut de Recherches Internationales Servier

Must not be taking: QT prolonging drugs

Disqualifiers: Recent HSCT, Severe infection, Heart failure, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 56

291 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new medication called AG-120 (also known as Ivosidenib or Tibsovo) to determine its safety and effectiveness in treating certain advanced blood cancers with a specific genetic change (IDH1 mutation). The study, in its early phase, tests different doses to identify the best one for future research. Individuals diagnosed with an advanced blood cancer that has the IDH1 mutation and who are willing to undergo blood and bone marrow tests might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the AG-120 trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude patients taking medications that prolong the QT interval (a measure of heart rhythm). It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that AG-120 is likely to be safe for humans?

Research shows that AG-120, also known as ivosidenib, may help treat certain blood cancers with a specific change called the IDH1 mutation. Previous studies have examined the safety of this treatment, suggesting that AG-120 is generally well-tolerated, meaning most people can take it without major problems.

Some patients might experience side effects, which are common with any treatment. In earlier research, serious side effects occurred in a small number of cases, but many side effects were manageable. It's important to note that this study is in its early stages, with the goal of finding the safest dose.

Since AG-120 is already approved for other uses, there is some confidence in its safety. However, the current study aims to ensure it is safe for this specific group of blood cancer patients. Researchers will closely monitor participants for any unwanted health effects throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood cancers, which often rely on chemotherapy or targeted therapies like tyrosine kinase inhibitors, AG-120 offers a novel approach by targeting a specific enzyme, IDH1, that is mutated in some cancer cells. This targeted action aims to halt the growth of cancer cells more precisely, potentially leading to fewer side effects compared to broader treatments. Researchers are excited about AG-120 because its oral administration could provide a convenient treatment option, allowing patients to take it at home rather than in a clinical setting.

What evidence suggests that AG-120 might be an effective treatment for blood cancers?

Research has shown that AG-120, also known as ivosidenib, holds promise for treating certain blood cancers with an IDH1 mutation. In patients with myelodysplastic syndrome, a type of blood disorder, studies found that nearly 39% achieved a complete response, and 83.3% experienced some level of response. The duration of response was not reached, suggesting the effects may last for many. In advanced blood cancers, patients tolerated AG-120 well, and it demonstrated strong clinical benefits. This evidence highlights AG-120's potential in addressing these challenging conditions. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

Adults (18+) with advanced blood cancers like AML or MDS that have a specific IDH1 mutation can join. They must be able to undergo regular bone marrow, blood, and urine tests, not be pregnant, and have an ECOG performance status of 0-2. Adequate liver and kidney function is required. Those with severe heart problems, recent cancer treatments within 14 days (except hydroxyurea), active infections including HIV or hepatitis B/C, CNS leukemia symptoms or history of it without clinical suspicion are excluded.

Inclusion Criteria

My platelet count is at least 20,000/µL, transfusions included.

My blood cancer has a specific IDH1 R132 gene mutation.

I am willing to undergo repeated bone marrow biopsies, blood, and urine tests.

Exclusion Criteria

I haven't had cancer treatment or radiotherapy in the last 14 days, except for hydroxyurea.

I do not have a severe infection or unexplained fever over 38.5°C.

I have severe heart failure or my heart's pumping ability is less than 40%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Cohorts of patients receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose

Up to 26 weeks

Continuous dosing in 28-day cycles

Dose Expansion

Four cohorts of patients receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose

Up to 26 weeks

Continuous dosing in 28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AG-120

Trial Overview AG-120 is being tested in patients with certain mutations in their blood cancer cells. The trial has two parts: first finding the highest dose people can take without too many side effects (dose escalation) and then giving more people this dose to see how well it works and if it's safe (dose expansion). There's also a special part for those whose myelodysplastic syndrome came back after treatment.

How Is the Trial Designed?

Group I: AG-120 Experimental Treatment 1 Intervention

AG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle.

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+

Published Research Related to This Trial

Ivosidenib, a targeted oral inhibitor of mutant IDH1, effectively reduces levels of the oncometabolite 2-hydroxyglutarate (2-HG) in patients with advanced hematologic malignancies, particularly at a dose of 500 mg once daily, achieving levels similar to those in healthy individuals.

The drug demonstrated favorable pharmacokinetics, with a long half-life of 72-138 hours and consistent efficacy across various patient demographics, indicating it is safe and effective for treating patients with IDH1 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation. Fan, B., Dai, D., DiNardo, CD., et al.[2022]

Ivosidenib, when combined with azacitidine, significantly improves event-free survival and overall survival in older adults or those with comorbidities suffering from IDH1-mutated acute myeloid leukemia, as shown in a phase 3 study with improved survival rates (HR 0.35 and HR 0.44).

The combination therapy also resulted in a higher complete remission rate (47% vs. 15% with placebo) and maintained a safety profile similar to ivosidenib alone, with notable adverse effects including differentiation syndrome and QT interval prolongation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation. Woods, A., Norsworthy, KJ., Wang, X., et al.[2023]

Ivosidenib, an oral medication targeting IDH1 mutations, was well-tolerated in a phase 1 study of 34 newly diagnosed acute myeloid leukemia (AML) patients, with a complete remission (CR) rate of 30.3% and a combined CR plus partial hematologic recovery rate of 42.4%.

The treatment led to significant outcomes, including 61.5% of patients remaining in remission after one year and 42.9% of transfusion-dependent patients becoming transfusion independent, demonstrating its efficacy in managing AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Roboz, GJ., DiNardo, CD., Stein, EM., et al.[2023]

Ivosidenib (Tibsovo®) is an oral medication that specifically inhibits mutated IDH1 enzymes, which are linked to the production of 2-hydroxyglutarate (2-HG), a metabolite that contributes to the development of certain cancers like acute myeloid leukaemia (AML).

The drug has received approval in the USA for treating patients with relapsed or refractory AML who have a specific IDH1 mutation, and ongoing clinical trials are exploring its efficacy in other cancers such as cholangiocarcinoma and glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib: First Global Approval. Dhillon, S.[2021]

Ivosidenib has shown the ability to induce remission in 30.4% of patients with relapsed or refractory acute myeloid leukemia that have IDH1 mutations, indicating its potential efficacy as a treatment.

The most common serious side effects observed were prolonged QT interval and IDH differentiation syndrome, highlighting the importance of monitoring for these conditions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib Deemed Safe, Effective in AML. [2019]

Ivosidenib is an FDA-approved treatment for adults with relapsed or refractory acute myeloid leukemia (R/R AML) with an IDH1 mutation, showing a complete remission (CR) + partial hematologic recovery (CRh) rate of 33% in a study of 174 patients over an 8.3-month follow-up.

While ivosidenib demonstrated short-term efficacy, including a median duration of response of 8.2 months and a 37% conversion rate from transfusion dependence to independence, serious adverse reactions such as differentiation syndrome and QT interval prolongation were noted, highlighting the need for ongoing safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation. Norsworthy, KJ., Luo, L., Hsu, V., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38640348/

Final phase 1 substudy results of ivosidenib for patients ... Ivosidenib is a first-in-class mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor with efficacy and tolerability in patients with advanced mIDH1 hematologic ...

2. ashpublications.org ashpublications.org/bloodadvances/article/8/15/4209/515789/Final-phase-1-substudy-results-of-ivosidenib-for

Final phase 1 substudy results of ivosidenib for patients with ... Key PointsIvosidenib resulted in a CR rate of 38.9% and an OR rate of 83.3% in mIDH1 R/R MDS; median duration of response was not reached.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02074839

NCT02074839 | Study of Orally Administered AG-120 in ... The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119812417

Ivosidenib (AG-120) in Mutant IDH1 AML and Advanced ... To report safety and efficacy data from the first-in-human phase 1 study of ivosidenib in patients with mIDH1 advanced hematologic malignancies ...

5. targetedonc.com targetedonc.com/view/long-term-follow-up-affirms-ivosidenib-s-sustained-benefit-in-idh1-mutated-aml

Long-Term Follow-Up Affirms Ivosidenib's Sustained ... New long-term data highlights the effectiveness and safety of ivosidenib with azacitidine for treating IDH1-mutated AML, improving patient ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02074839

NCT02074839 | Study of Orally Administered AG-120 in ... The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced ...

7. ashpublications.org ashpublications.org/bloodadvances/article/9/20/5177/546354/Long-term-results-from-the-AGILE-study-of

Long-term results from the AGILE study of azacitidine plus ... This study presents long-term OS and safety data from the AGILE study, and the depth of response to ivosidenib-azacitidine using NGS-based molecular measurable ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7012

Updated efficacy and safety data from the AGILE study in ... IVO plus azacitidine (AZA) significantly improved event-free survival (EFS), overall survival (OS), complete remission (CR), and CR or CR with partial ...