What side effects are associated with this type of intervention?

Common treatments for solid tumors, including small molecule inhibitors like IDE397 and other agents such as taxanes (docetaxel, paclitaxel) and sacituzumab govitecan, often result in a range of side effects. These can include gastrointestinal issues (nausea, vomiting, diarrhea), hematologic toxicities (neutropenia, anemia), fatigue, and musculoskeletal pain. Additionally, taxanes are known for causing peripheral neuropathy and hypersensitivity reactions, while sacituzumab govitecan can lead to neutropenia and diarrhea. Monitoring and managing these side effects are crucial for maintaining patient quality of life during treatment.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of solid tumors, particularly those with specific genetic mutations or molecular targets. For example, pembrolizumab, an anti-PD-1 antibody, has been approved for various solid tumors, including melanoma and non-small cell lung cancer, based on its ability to enhance the immune response against cancer cells. Similarly, drugs like vemurafenib and dabrafenib, which target the BRAF V600E mutation, have been approved for the treatment of melanoma. These approvals highlight the trend towards personalized medicine in oncology, where treatments are tailored based on the genetic profile of the tumor.

What other types of research exist?

Promising novel alternatives to IDE397 for solid tumors include ONC201, a selective DRD2 antagonist, which has shown efficacy in treating H3 K27M-mutant diffuse midline gliomas, and I-387, an antimitotic agent with potent in vitro and in vivo antitumor activity. Additionally, nanodiamond-mitoxantrone complexes are being evaluated for their enhanced drug retention in chemoresistant cancer cells.

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Small Molecule Inhibitor

IDE397 for Solid Tumors

Phase 1

Recruiting

Research Sponsored by IDEAYA Biosciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must be at least 18 years of age

Advanced or metastatic solid tumor that has progressed on at least one prior line of treatment or is intolerant to additional effective standard therapy

Must not have

Known symptomatic brain metastases

Radiation therapy within 2 weeks prior to study entry

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to IDE397 which could affect various organs due to its mechanism as a MAT2A inhibitor. Chemotherapy may cause hair loss, nausea, fatigue, increased risk of infection among others. The exact side effects will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My cancer has worsened after treatment or I cannot tolerate standard therapy.

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My cancer has a specific genetic change called MTAP loss.

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I can swallow and keep down pills.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have brain metastases that are causing symptoms.

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I have not had radiation therapy in the last 2 weeks.

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I have had radiation to more than a quarter of my bone marrow.

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I have an ongoing liver or bile duct condition.

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I have serious heart problems.

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I have a diagnosed brain tumor.

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I have been treated with a MAT2A or PRMT inhibitor before.

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I am using or might need strong CYP3A4/5 inhibitors or inducers.

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I currently have an infection that isn't under control.

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My stomach or intestines are not working properly.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting Toxicities (DLTs) of IDE397

Dose-limiting Toxicities (DLTs) of IDE397 in combination with docetaxel or paclitaxel or sacituzumab govitecan

Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397

+2 more

Secondary study objectives

Drug interaction between IDE397 and docetaxel or paclitaxel or sacituzumab govitecan

Pharmacodynamic effect of IDE397 as a single agent and in combination with docetaxel or paclitaxel or sacituzumab govitecan

Plasma Pharmacokinetics of IDE397 and metabolite

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (Urothelial)Experimental Treatment2 Interventions

Group II: Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (Urothelial)Experimental Treatment2 Interventions

Group III: Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial)Experimental Treatment3 Interventions

Group IV: Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial)Experimental Treatment3 Interventions

Group V: Part 2: Monotherapy Dose Expansion (NSCLC, EG and Urothelial)Experimental Treatment1 Intervention

Group VI: Part 1: Dose Escalation Monotherapy (Solid Tumors)Experimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Docetaxel

1995

Completed Phase 4

~6550

Paclitaxel

2011

Completed Phase 4

~5450

Sacituzumab govitecan

2017

Completed Phase 3

~530

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors often target specific genetic mutations or cellular processes essential for tumor growth. For example, IDE397 inhibits methionine adenosyltransferase 2 alpha (MAT2A), which is crucial for methionine metabolism in cancer cells with MTAP deletions. This inhibition disrupts the tumor's metabolic processes, leading to reduced tumor growth. Other treatments may inhibit protein synthesis, such as the estrogen metabolite 2-methoxyestradiol, or target signaling pathways like the Akt-mTOR pathway. These targeted therapies are vital for solid tumor patients as they offer more precise and effective treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Transition state analogue of MTAP extends lifespan of APCMin/+ mice.The histone demethylase JMJD2A promotes glioma cell growth via targeting Akt-mTOR signaling.PAMs inhibits monoamine oxidase a activity and reduces glioma tumor growth, a potential adjuvant treatment for glioma.