IDE397 for Solid Tumors

Recruiting at33 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: IDEAYA Biosciences

Must not be taking: CYP3A4/5 inhibitors, inducers

Disqualifiers: Brain metastases, CNS malignancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing IDE397, a new drug, in adults with advanced cancers that don't respond to usual treatments. The drug works by blocking a protein that cancer cells need to grow.

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.

What data supports the effectiveness of the drug IDE397 for treating solid tumors?

Research shows that MAT2A inhibitors, like IDE397, can effectively target cancer cells by reducing a key molecule (SAM) needed for their growth, especially in cancers with specific genetic deletions (MTAP-deleted cancers). These inhibitors have shown promise in stopping cancer cell growth and causing DNA damage in lab studies, suggesting potential effectiveness in treating solid tumors. ^{1 2 3 4 5}

What makes the drug IDE397 unique for treating solid tumors?

IDE397 is unique because it targets the MAT2A enzyme, which is crucial for the growth of certain aggressive tumors that lack effective treatments. It works by reducing levels of a molecule called S-adenosylmethionine (SAM), which is essential for tumor cell growth, especially in cancers with a specific genetic deletion (MTAP-deleted cancers). ^{1 3 5 6 7}

Research Team

Jasgit Sachdev, MD

Principal Investigator

IDEAYA Biosciences

Eligibility Criteria

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 am 18 years old or older.

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

Able to comply with contraceptive/barrier requirements

Exclusion Criteria

I have serious heart problems.

I have brain metastases that are causing symptoms.

Known or suspected hypersensitivity to IDE397/excipients or components

Trial Timeline

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

Treatment Details

Interventions

• IDE397 (Small Molecule Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fluorinated N,N-dialkylaminostilbenes repress colon cancer by targeting methionine S-adenosyltransferase 2A. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Overview of Methionine Adenosyltransferase 2A (MAT2A) as an Anticancer Target: Structure, Function, and Inhibitors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Discovery of novel methionine adenosyltransferase 2A (MAT2A) allosteric inhibitors by structure-based virtual screening. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A. [2018]

5. United States 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model. [2021]

7. United States 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. [2021]