IDE397 for Solid Tumors

Recruiting at 38 trial locations

Overseen By IDEAYA Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: IDEAYA Biosciences

Must not be taking: CYP3A4/5 inhibitors, inducers

Disqualifiers: Brain metastases, CNS malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IDE397, designed to address advanced or metastatic solid tumors that have not responded well to standard treatments. IDE397 targets a specific enzyme, MAT2A, and is being evaluated both alone and in combination with other cancer drugs. The goal is to assess the safety and effectiveness of these treatments for individuals whose cancer has a specific genetic feature known as MTAP deletion. Suitable candidates have advanced cancer that has not responded to other treatments and possess the genetic marker MTAP deletion. As a Phase 1 trial, this research aims to understand how IDE397 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use drugs that strongly affect certain liver enzymes (CYP3A4/5 inhibitors or inducers). 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 IDE397, a type of drug, has a manageable safety profile for patients with certain cancers. In earlier studies, patients taking only IDE397 generally tolerated it well. When combined with sacituzumab govitecan, early trials showed promising results, indicating the combination was safe.

IDE397 has also been tested with other cancer drugs like docetaxel and paclitaxel. While specific side effects from these combinations aren't detailed, the ongoing trial phase means researchers are still determining the safest doses.

Overall, even though IDE397 remains in early testing, current data suggests it is generally well-tolerated. However, joining a clinical trial involves accepting some uncertainty until more information becomes available. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about IDE397 because it targets tumors with a unique approach. Unlike many standard treatments for solid tumors, which often involve chemotherapy or radiation, IDE397 targets a specific metabolic pathway in cancer cells, known as MAT2A. This approach aims to disrupt the cancer cells' metabolism, effectively starving them and inhibiting their growth. In addition, IDE397 is being explored both as a monotherapy and in combination with other drugs like sacituzumab govitecan, docetaxel, and paclitaxel, potentially enhancing its effectiveness against tough-to-treat tumors. This targeted strategy offers hope for more precise and potentially less toxic cancer treatment options.

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

Research has shown that IDE397, a drug that blocks a specific protein, may help treat solid tumors with certain genetic changes. Participants in this trial may receive IDE397 alongside other cancer drugs. For instance, in the combination dose escalation and expansion arms with sacituzumab govitecan (SG), 57% of patients with a type of bladder cancer saw their tumors shrink or stop growing, indicating positive results for more than half of the patients. IDE397 is also being tested with other drugs like docetaxel or paclitaxel in separate arms, though detailed results are not yet available. These findings suggest that IDE397 could be effective for certain types of cancer, especially when combined with other treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Jasgit Sachdev, MD

Principal Investigator

IDEAYA Biosciences

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific genetic change (MTAP deletion) and haven't responded to standard treatments. Participants must be over 18, recovered from previous therapies, able to take oral medication, and willing to use contraception. They should not have significant heart issues, active liver disease, brain metastases or be on certain drugs affecting the liver enzyme CYP3A4/5.

Inclusion Criteria

I have recovered from the side effects of my last treatment.

Able to comply with contraceptive/barrier requirements

I can do most of my daily activities but may need help after talking to a medical expert.

Exclusion Criteria

I have serious heart problems.

I have brain metastases that are causing symptoms.

Known or suspected hypersensitivity to IDE397/excipients or components

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive IDE397 as a single agent to determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

21-28 days

Combination Dose Escalation

Participants receive IDE397 in combination with docetaxel, paclitaxel, or sacituzumab govitecan to evaluate safety and preliminary anti-tumor activity

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IDE397

Trial Overview

The study tests IDE397 alone or with chemotherapy drugs docetaxel or paclitaxel in patients with MTAP-deleted tumors. It's an early-phase trial assessing safety, how the body processes the drug (pharmacokinetics), its effects on the tumor (pharmacodynamics), and potential anti-cancer activity.

How Is the Trial Designed?

Group I: Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (Urothelial) Experimental Treatment 2 Interventions

Group II: Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (Urothelial) Experimental Treatment 2 Interventions

Group III: Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial) Experimental Treatment 3 Interventions

Group IV: Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial) Experimental Treatment 3 Interventions

Group V: Part 2: Monotherapy Dose Expansion (NSCLC, EG and Urothelial) Experimental Treatment 1 Intervention

Group VI: Part 1: Dose Escalation Monotherapy (Solid Tumors) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

IDEAYA Biosciences

Lead Sponsor

Trials

6

Recruited

1,300+

Published Research Related to This Trial

PF-9366 is a newly identified inhibitor of the enzyme methionine adenosyltransferase 2A (Mat2A), which plays a crucial role in cancer metabolism by regulating S-Adenosyl-L-methionine (SAM) levels.

The study reveals that PF-9366 binds to an allosteric site on Mat2A, altering its activity based on the levels of methionine or SAM, suggesting a potential therapeutic strategy for targeting Mat2A in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A. Quinlan, CL., Kaiser, SE., Bolaños, B., et al.[2018]

MAT2A is a crucial enzyme in the methionine cycle and is a promising target for cancer therapy, particularly in tumors with MTAP loss.

Several MAT2A inhibitors have been developed, with three currently in clinical trials, highlighting their potential efficacy in treating solid tumors and lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Methionine Adenosyltransferase 2A (MAT2A) as an Anticancer Target: Structure, Function, and Inhibitors. Li, C., Gui, G., Zhang, L., et al.[2022]

The co-deletion of the MTAP gene with the CDKN2A tumor-suppressor gene in about 15% of cancers leads to aggressive tumors, making MAT2A a promising synthetic lethal target for these cancers.

Potent MAT2A inhibitors significantly reduce S-adenosylmethionine levels and show antiproliferative effects in MTAP-deleted cancer cells, suggesting a potential treatment strategy that could be enhanced by combining MAT2A inhibitors with antimitotic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage. Kalev, P., Hyer, ML., Gross, S., et al.[2021]

FIDAS agents, which inhibit the enzyme MAT2A involved in S-adenosylmethionine (SAM) synthesis, effectively reduce the growth of colorectal cancer (CRC) cells both in laboratory settings and in live animal models, indicating their potential as a cancer treatment.

The study identified MAT2A as the direct target of FIDAS agents, and demonstrated that reducing MAT2A levels through genetic methods also inhibited CRC cell growth, highlighting the importance of MAT2A in cancer proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorinated N,N-dialkylaminostilbenes repress colon cancer by targeting methionine S-adenosyltransferase 2A. Zhang, W., Sviripa, V., Chen, X., et al.[2021]

Researchers developed highly potent and selective MAT2A inhibitors that effectively reduce levels of S-adenosyl methionine (SAM) in cancer cells, overcoming previous challenges with cellular adaptations.

These MAT2A inhibitors selectively block the growth of cancer cells lacking the MTAP gene, showing promise for targeted cancer therapy and leading to the progression of AG-270 into clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion. Konteatis, Z., Travins, J., Gross, S., et al.[2021]

A virtual screening campaign identified two new series of MAT2A inhibitors, which are promising drug targets for cancer treatment, demonstrating nanomolar activity in inhibiting MAT2A.

The binding modes of these compounds were confirmed through X-ray crystallography, and they showed effective inhibition of cell proliferation in a specific cancer cell line, indicating their potential for further development in drug discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of novel methionine adenosyltransferase 2A (MAT2A) allosteric inhibitors by structure-based virtual screening. Kalliokoski, T., Kettunen, H., Kumpulainen, E., et al.[2023]

MAT2a is a promising target for treating cancers with co-deletion of p16 and MTAP genes, as inhibiting this enzyme can effectively reduce tumor growth in these specific cancer types.

A newly developed MAT2a inhibitor, compound 28, demonstrated the ability to decrease S-adenosylmethionine (SAM) levels and inhibit the proliferation of MTAP-null cancer cells, leading to a significant antitumor response in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model. De Fusco, C., Schimpl, M., Börjesson, U., et al.[2021]

Citations

1.

ir.ideayabio.com

ir.ideayabio.com/2025-09-08-IDEAYA-Biosciences-Announces-Positive-Data-From-Phase-1-2-Combination-Trial-of-IDE397,-a-potential-first-in-class-MAT2A-inhibitor,-and-Trodelvy-R-in-MTAP-Deletion-Urothelial-Cancer

News Releases

Overall response rate (ORR) of 57% (4/7; 3cPR+1uPR) in patients treated with a combination of 30 mg IDE397 plus 7.5mg/kg Trodelvy® (Dose ...

2.

prnewswire.com

prnewswire.com/news-releases/ideaya-biosciences-announces-positive-data-from-phase-12-combination-trial-of-ide397-a-potential-first-in-class-mat2a-inhibitor-and-trodelvy-in-mtap-deletion-urothelial-cancer-302548584.html

IDEAYA Biosciences Announces Positive Data From ...

Overall response rate (ORR) of 57% (4/7; 3cPR+1uPR) in patients treated with a combination of 30 mg IDE397 plus 7.5mg/kg Trodelvy® (Dose ...

3.

onclive.com

onclive.com/view/ide397-plus-sacituzumab-govitecan-elicits-responses-in-mtap-deletion-urothelial-cancer

IDE397 Plus Sacituzumab Govitecan Elicits Responses in ...

IDE397 plus sacituzumab govitecan shows preliminary efficacy in MTAP-deletion urothelial cancer.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04794699

NCT04794699 | Study of IDE397 in Participants With Solid ...

This is a Phase 1, open-label, multicenter, dose escalation and expansion study of the safety, PK, PD, and preliminary anti-tumor activity of IDE397.

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS892

Phase 1 dose escalation (DEs) & expansion (DEx) study to ...

Background: IDE397, an allosteric MAT2A inhibitor (MAT2Ai) has shown synthetic lethality in MTAPdel tumors. MTAPdel in UC (~26%; TCGA database) ...

6.

onclive.com

onclive.com/view/ide397-shows-early-antitumor-activity-safety-in-mtap-deletion-urothelial-cancer-and-nsclc

IDE397 Shows Early Antitumor Activity, Safety in MTAP ...

The MAT2A inhibitor IDE397 showed antitumor activity, generated responses, and had a manageable safety profile among patients with MTAP-deletion urothelial ...

7.

aacrjournals.org

aacrjournals.org/clincancerres/article/30/10_Supplement/B027/745272/Abstract-B027-The-MAT2A-inhibitor-IDE397-a-novel

The MAT2A inhibitor IDE397: a novel combination backbone ...

IDE397, a potent small molecule inhibitor of MAT2A, was developed to selectively exploit this synthetic lethal vulnerability in MTAP −/− tumors.