What is the mechanism of action of this treatment?

The most common treatments for solid tumors include chemotherapy, targeted therapy, immunotherapy, and radiation therapy. Chemotherapy works by killing rapidly dividing cells, while targeted therapies, such as mutant IDH inhibitors like LY3410738, specifically inhibit cancer cell growth by blocking molecular pathways essential for tumor survival and proliferation. Immunotherapy boosts the body's immune system to recognize and destroy cancer cells, and radiation therapy uses high-energy particles to damage the DNA of cancer cells, leading to cell death. For patients with solid tumors, understanding these mechanisms is crucial as it helps in selecting the most effective treatment strategy, potentially improving outcomes and minimizing side effects.

What side effects are associated with this type of intervention?

Common treatments for solid tumors, particularly those involving IDH inhibitors like LY3410738, often include side effects such as fatigue, nausea, diarrhea, and decreased appetite. Other potential side effects can include elevated liver enzymes, anemia, and leukopenia. These side effects are generally manageable but can vary in severity among patients.

What prior FDA approvals exist?

The FDA has approved several treatments for solid tumors with IDH1 or IDH2 mutations. For instance, ivosidenib (Tibsovo) is approved for the treatment of IDH1-mutant cholangiocarcinoma. Additionally, enasidenib (Idhifa) is approved for IDH2-mutant acute myeloid leukemia, which, while not a solid tumor, shares a similar target mechanism. These drugs inhibit the mutant forms of the IDH enzymes, thereby reducing the production of the oncometabolite 2-hydroxyglutarate, which is implicated in tumorigenesis.

What other types of research exist?

Promising alternatives to LY3410738 for patients with solid tumors and IDH mutations include ONC201, a selective DRD2 antagonist, which has shown efficacy in gliomas, and immune checkpoint inhibitors like pembrolizumab and nivolumab, which have demonstrated activity in various solid tumors. Additionally, targeted therapies such as infigratinib and futibatinib for FGFR2 fusion-positive cholangiocarcinoma may also be considered based on the specific genetic profile of the tumor.

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IDH Inhibitor

LY3410738 for Solid Tumors

Phase 1

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

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

Must have

Cholangiocarcinoma patients with IDH1 R132, IDH2 R140, or IDH2 R172 mutations

Ability to swallow capsules or tablets.

Must not have

Patients with cholangiocarcinoma: underwent hepatic radiation, chemoembolization and radiofrequency ablation, radioembolization or other locoregional therapy <4 weeks, have history of hepatic encephalopathy of any grade, have ascites requiring intervention such as diuretics or paracentesis, have ongoing cholangitis, have mixed hepatocellular biliary tract cancer histology or history of liver transplant.

Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 at the time of starting study treatment except for alopecia.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new oral drug called LY3410738 in patients with advanced solid tumors that have specific genetic mutations. The drug works by blocking abnormal enzymes to potentially stop or slow cancer growth.

Who is the study for?

Adults with advanced solid tumors that have specific mutations (IDH1 R132, IDH2 R140, or IDH2 R172) and are not responding to standard treatments. They should be in good physical condition (ECOG 0-1), able to swallow pills, and willing to use birth control. People who've had certain prior treatments or have active infections, uncontrolled diseases, brain metastases requiring steroids, or a history of severe immune-related side effects from other drugs can't join.

What is being tested?

The trial is testing LY3410738—an oral drug—on its own for safety and early signs of effectiveness against tumors with particular genetic changes. It's an open-label study where everyone knows what treatment they're getting. The trial includes patients with cancers like cholangiocarcinoma and glioma after some previous treatments failed.

What are the potential side effects?

Possible side effects aren't listed here but based on the nature of clinical trials for cancer drugs like LY3410738 which targets specific enzymes mutated in cancer cells; fatigue, nausea, liver issues, diarrhea or constipation could occur among others.

Eligibility Criteria

Inclusion Criteria

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

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My cholangiocarcinoma has specific IDH1 or IDH2 mutations.

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I can swallow pills.

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I have or had serious lung inflammation that needed strong medication.

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My cancer has a specific genetic mutation (IDH1 or IDH2) confirmed by a certified lab.

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I have been treated with anti-PD 1 or anti-PD L1 therapies before.

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I am fully active or can carry out light work.

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My cholangiocarcinoma has been confirmed and I've had 1-2 treatments, but no IDH1 inhibitors.

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My bile duct cancer cannot be removed by surgery.

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My bile duct cancer is advanced or has spread, and I've had at least one treatment.

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I have had severe side effects from immune therapy.

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I have an autoimmune disease treated with medication in the last 2 years.

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I am 18 years old or older.

Exclusion Criteria

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

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I have cholangiocarcinoma and have not undergone specific liver treatments in the last 4 weeks, nor do I have complications like ascites, encephalopathy, ongoing cholangitis, mixed cancer types, or a liver transplant history.

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I don't have severe side effects from past treatments, except for hair loss.

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I do not have HIV due to potential medication interactions.

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I am not on strong medications that affect liver enzymes or drug transporters.

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I do not have a condition that affects how my body absorbs medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumabExperimental Treatment4 Interventions

Phase 1 dose expansion - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of LY3410738 alone or in combination with gemcitabine plus cisplatin or in combination with durvalumab

Group II: LY3410738Experimental Treatment1 Intervention

Phase 1 dose escalation - Multiple doses of LY3410738

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cisplatin

2013

Completed Phase 3

~3120

Durvalumab

2017

Completed Phase 2

~3750

Gemcitabine

2017

Completed Phase 3

~1920

LY3410738

2021

Completed Phase 1

~110

0 / 17Eligibility 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

The most common treatments for solid tumors include chemotherapy, targeted therapy, immunotherapy, and radiation therapy. Chemotherapy works by killing rapidly dividing cells, while targeted therapies, such as mutant IDH inhibitors like LY3410738, specifically inhibit cancer cell growth by blocking molecular pathways essential for tumor survival and proliferation. Immunotherapy boosts the body's immune system to recognize and destroy cancer cells, and radiation therapy uses high-energy particles to damage the DNA of cancer cells, leading to cell death. For patients with solid tumors, understanding these mechanisms is crucial as it helps in selecting the most effective treatment strategy, potentially improving outcomes and minimizing side effects.

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