What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as cetuximab, irinotecan, oxaliplatin, and FOLFOXIRI, are associated with several side effects. Cetuximab can cause skin toxicity, rash, diarrhea, nausea, and vomiting. Irinotecan-based therapies may lead to diarrhea and skin reactions. Oxaliplatin is known for causing peripheral neuropathy and gastrointestinal issues. FOLFOXIRI, a combination regimen, can result in diarrhea, rash, and other gastrointestinal disturbances. These side effects are important considerations when evaluating treatment options for colorectal cancer.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for colorectal cancer, particularly for patients with specific genetic mutations. Notably, cetuximab and panitumumab are approved for patients with wild-type KRAS metastatic colorectal cancer, as they target the epidermal growth factor receptor (EGFR). Additionally, encorafenib in combination with cetuximab is approved for patients with BRAF V600E-mutant metastatic colorectal cancer. These treatments highlight the importance of genetic profiling in colorectal cancer to tailor targeted therapies. The study drug LY3537982, a KRAS G12C inhibitor, represents a novel approach targeting a specific KRAS mutation, which is a promising area of research given the limited options for KRAS-mutant colorectal cancer.

What other types of research exist?

Promising alternatives to LY3537982 for colorectal cancer patients include: 1) CMAB009 plus irinotecan, which has shown superior efficacy as a second-line treatment in KRAS wild-type mCRC patients. 2) Panitumumab combined with mFOLFOX6, which has demonstrated effectiveness in patients with wild-type KRAS exon 2 metastatic colorectal cancer. 3) Cetuximab combined with FOLFIRI or FOLFOX, which has been shown to reduce disease progression and increase response rates in KRAS wild-type mCRC patients.

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Small Molecule Inhibitor

LY3537982 for Cancer

Phase 1 & 2

Recruiting

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

Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or circulating tumor deoxyribonucleic acid (DNA)

Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Must not have

Have a serious cardiac condition

Disease suitable for local therapy administered with curative intent

Timeline

Screening 3 weeks

Treatment Varies

Follow Up estimated up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called LY3537982 in cancer patients with the KRAS G12C mutation. It targets this mutation to stop cancer cells from growing. The study includes patients who haven't responded to other treatments or cannot tolerate them. LY3537982 is a new drug targeting the KRAS G12C mutation, similar to previously approved drugs like sotorasib and adagrasib.

Who is the study for?

This trial is for cancer patients with a KRAS G12C mutation who've tried or can't tolerate standard treatments. It's open to those with certain cancers, like pancreatic and lung, if they have measurable disease, good organ function, an ECOG status of 0 or 1, and agree to use contraception. Some untreated NSCLC patients may join under specific conditions.

What is being tested?

The study tests LY3537982's safety and effectiveness in treating various cancers with the KRAS G12C mutation. Patients will also receive other drugs like Pemetrexed and Pembrolizumab depending on their condition. The trial aims to include participants for up to four years.

What are the potential side effects?

Potential side effects could include reactions related to the immune system due to Pembrolizumab, issues from chemotherapy agents like Pemetrexed (nausea, fatigue), as well as risks associated with new drug LY3537982 which are being studied.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has a KRAS G12C mutation.

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I am fully active or can carry out light work.

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I have had treatment with oxaliplatin or irinotecan for advanced colorectal cancer.

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My cancer is advanced, cannot be surgically removed, and/or has spread.

Exclusion Criteria

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

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I have a serious heart condition.

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My condition can be treated with the goal of curing it.

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I currently have an infection that is not being treated.

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I have not been diagnosed or treated for another cancer within the last 3 years.

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I had severe side effects from previous immunotherapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ estimated up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~estimated up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and estimated up to 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

Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy

Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents

Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab

Secondary study objectives

To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)

To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR)

To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)

+8 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: LY3537982 (Dose Optimization)Experimental Treatment3 Interventions

LY3537982 administered orally either alone or with another investigational agent

Group II: LY3537982 (Dose Expansion)Experimental Treatment6 Interventions

LY3537982 administered orally either alone or with another investigational agent.

Group III: LY3537982 (Dose Escalation)Experimental Treatment1 Intervention

LY3537982 administered orally.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

LY3537982

2023

Completed Phase 1

~130

Pembrolizumab

2017

Completed Phase 3

~2810

Cetuximab

2011

Completed Phase 3

~2480

Pemetrexed

2014

Completed Phase 3

~5550

Cisplatin

2013

Completed Phase 3

~3120

Carboplatin

2014

Completed Phase 3

~6120

0 / 9Eligibility 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 colorectal cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy drugs like fluorouracil and oxaliplatin work by interfering with DNA replication, leading to cancer cell death. Targeted therapies, such as cetuximab and bevacizumab, inhibit specific molecules involved in cancer growth and spread; cetuximab targets the epidermal growth factor receptor (EGFR), while bevacizumab inhibits vascular endothelial growth factor (VEGF). KRAS G12C inhibitors, like LY3537982, specifically target the KRAS G12C mutation, blocking the abnormal signaling pathways that drive cancer cell proliferation. These treatments are crucial as they offer more personalized and effective options, potentially leading to better outcomes and fewer side effects for colorectal cancer patients.

Targeted therapies for gallbladder cancer: an overview of agents in preclinical and clinical development.Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6.