AG-120 for Chondrosarcoma

Recruiting at 6 trial locations

Overseen By Ciara Kelly, MBBCh BAO

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4 inducers, QT prolongers

Disqualifiers: Brain metastasis, Active cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether AG-120 (also known as Ivosidenib or Tibsovo) is a safe and effective treatment for individuals with advanced or recurrent chondrosarcoma, a type of bone cancer with a specific IDH1 gene mutation. The researchers aim to determine if this medication can slow down or shrink the cancer in these patients. Participants should have advanced chondrosarcoma confirmed as grade 2 or 3 and a known IDH1 gene mutation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires a washout period (time without taking certain medications) for some treatments. If you are taking strong CYP3A4 inducers or certain other medications, you may need to switch to different ones before starting the trial. 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 has shown that AG-120, also known as ivosidenib, was tested for safety in people with chondrosarcoma, a type of bone cancer. In earlier studies, about 71.4% of patients experienced some side effects from the treatment, but these were usually manageable. Serious side effects occurred in 28.6% of patients, but none were life-threatening. Overall, AG-120 was well-tolerated by patients. This indicates that while side effects can occur, the treatment is considered relatively safe for people with this specific type of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chondrosarcoma?

AG-120 is unique because it specifically targets a genetic mutation known as IDH1, which is found in some cases of chondrosarcoma. Unlike the standard treatments for chondrosarcoma, which typically involve surgery, radiation, or chemotherapy, AG-120 works by inhibiting the mutant IDH1 enzyme, potentially stopping the cancer cells from growing and dividing. Researchers are excited about AG-120 because it offers a targeted approach, which might result in fewer side effects and more effective control of the tumor compared to conventional treatments.

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

Research shows that AG-120, also known as ivosidenib, may help treat chondrosarcoma with an IDH1 mutation. In earlier studies, 52% of patients with this mutation experienced stable disease, meaning their cancer did not worsen for a period of time. Another study found that the median time before the cancer progressed was 7.4 months. These results suggest that AG-120 can slow cancer growth in some patients. While not everyone responds the same way, this data offers hope for those with this specific mutation. Participants in this trial will receive AG-120 to evaluate its effectiveness in treating locally advanced/metastatic or recurrent operable chondrosarcoma. ^{2 5 6 7 8}

Who Is on the Research Team?

Ciara Kelly, MBBCh BAO

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or recurrent chondrosarcoma and an IDH1 gene mutation. Participants must have stable vital organ functions, no severe infections, not be pregnant or breastfeeding, agree to use two forms of contraception if they can reproduce, and not have used certain other treatments recently.

Inclusion Criteria

I can take pills by mouth.

You are expected to live for at least four more months.

I am not pregnant or have confirmed contraception use if capable of becoming pregnant.

Exclusion Criteria

My heart's pumping ability is below 40% as shown by recent tests.

I haven't had radiotherapy or local treatment for cancer spread in the last 2 weeks.

I have previously been treated with an IDH1 inhibitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AG-120 for the treatment of IDH1 mutant chondrosarcoma

16 weeks

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 The study tests AG-120's effectiveness and safety in treating chondrosarcoma with the IDH1 mutation. It examines how well patients respond to this oral medication when their cancer has returned or spread despite previous treatment.

How Is the Trial Designed?

Group I: Chondrosarcoma Experimental Treatment 1 Intervention

Participants will have locally advanced/metastatic or recurrent operable chondrosarcoma

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Agios Pharmaceuticals, Inc.

Industry Sponsor

Trials

55

Recruited

4,200+

Published Research Related to This Trial

In a phase I study involving 21 patients with advanced chondrosarcoma, ivosidenib treatment resulted in a significant reduction of the oncometabolite D-2-hydroxyglutarate (2-HG) in all patients, indicating effective targeting of the mutant IDH1 enzyme.

The treatment demonstrated minimal toxicity, with most adverse events being mild (grade 1 or 2), and a median progression-free survival of 5.6 months, suggesting potential for durable disease control in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma. Tap, WD., Villalobos, VM., Cote, GM., et al.[2021]

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]

In a phase II trial involving 45 patients with advanced chondrosarcoma, the Hedgehog pathway inhibitor GDC-0449 showed a 6-month clinical benefit rate of 25.6%, which did not meet the target of 40% for efficacy.

The treatment was associated with manageable side effects, primarily grade 1 or 2 symptoms like myalgia and alopecia, suggesting that while GDC-0449 did not achieve its primary endpoint, it may still have potential benefits for certain patients with specific tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/US and French National Cancer Institute Single-Arm Phase II Collaborative Study. Italiano, A., Le Cesne, A., Bellera, C., et al.[2022]

In a phase 2 study involving 47 patients with unresectable or metastatic conventional chondrosarcoma, pazopanib demonstrated a disease control rate of 43% at 16 weeks, indicating its potential effectiveness in managing this type of cancer.

The median overall survival for patients was 17.6 months, with manageable side effects, primarily hypertension (26%) and elevated liver enzymes (9%), suggesting that pazopanib is a relatively safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma. Chow, W., Frankel, P., Ruel, C., et al.[2021]

The JJ012 chondrosarcoma cell line showed significantly higher tumor growth and invasive properties compared to the FS090 cell line, making it a more relevant model for studying chondrosarcoma in vivo.

The established JJ012 mouse model successfully mimics human chondrosarcoma characteristics, including local bone invasion and lung metastasis, providing a valuable platform for testing new targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis. Clark, JC., Akiyama, T., Dass, CR., et al.[2021]

BH3 mimetics ABT-737 and ABT-263 effectively inhibit the growth of chondrosarcoma cells in vitro and induce apoptosis, suggesting a potential new treatment approach for this chemotherapy-resistant cancer.

In vivo studies using a mouse model demonstrated that ABT-263 not only inhibited chondrosarcoma growth but also improved survival, highlighting its efficacy as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models. Morii, T., Ohtsuka, K., Ohnishi, H., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7238491/

Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib All 21 patients with chondrosarcoma were included for efficacy evaluation; 11 (52%) experienced SD as the best overall response by RECIST, six (29%) had PD, one ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11532

Phase I study of the mutant IDH1 inhibitor ivosidenib All responses occurred after > 2 years on treatment. Median PFS was 7.4 months (95% CI: 2.0-61.3). Conclusions: In pts with IDH1 mutated ...

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04278781?term=chondrosarcoma&draw=2&rank=1

AG-120 in People With IDH1 Mutant Chondrosarcoma | ... This study is being done to see whether AG-120 is an effective and safe treatment for people with advanced/metastatic or recurrent chondrosarcoma that has IDH1 ...

4. servier.us servier.us/blog/servier-announces-expansion-of-its-tibsovo-ivosidenib-development-program-investigating-its-safety-and-efficacy-in-patients-living-with-idh1-mutated-cancers-in-both-hematological-malignancies-and-so/

Servier Announces Expansion of its Tibsovo (ivosidenib) ... Servier today announced updates to two of its Phase 3 programs evaluating TIBSOVO (ivosidenib tablets) in isocitrate dehydrogenase 1 (IDH1)-mutated cancers.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS11582

Phase 3 study of ivosidenib vs placebo in locally advanced ... The current phase 3 CHONQUER study was designed to assess the efficacy and safety of ivosidenib treatment in patients with grades 1, 2 and 3 conventional CS.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40100120/

Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib - PubMed Of the 21 patients with CS, 71.4% and 28.6% had treatment-related and serious adverse events, respectively, but no serious adverse events were ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/31/11/2108/762527/Phase-I-Study-of-the-Mutant-IDH1-Inhibitor

Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Long ... In this phase I dose-escalation and expansion study, ivosidenib demonstrated clinical activity and was well tolerated in patients with mIDH1 conventional CS.

8. serviermedical.us serviermedical.us/materials/D8fPZYs7NMBNeGfGTN3QETCQGvFVy2pXWyFBB3qw.pdf

Chondrosarcoma ASCO Poster FINAL 12MAY2023_V4 Here we report long term safety and efficacy results of IVO among the conventional CS population based on the data cut-off date of 15. September 2022. • To ...