A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors

Lilly

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor; Non-small Cell Lung Cancer; Pancreatic Ductal Adenocarcinoma; Metastatic Solid Tumor; Colorectal Cancer

Treatments: Drug: Pembrolizumab; Drug: Irinotecan; Drug: 5Fluorouracil; Drug: Cisplatin; Drug: Leucovorin; Drug: Pemetrexed; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Carboplatin; Drug: Cetuximab; Drug: Oxaliplatin; Drug: LY4066434.

Study type: Interventional

Funder types: Industry

Identifiers

NCT06607185

J5Q-OX-JRDA (Other Identifier)

27237

Details and patient eligibility

About

The main purpose of the study is to assess whether the study drug, LY4066434, is safe and tolerable when administered to participants with locally advanced or metastatic solid tumors with certain KRAS mutations. LY4066434 will be given alone or in combination with other treatments. The study will have 2 parts: monotherapy dose escalation and dose optimization. The study is expected to last up to approximately 5 years.

Enrollment: 750 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have evidence of KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor DNA
• Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer
• Have measurable disease per RECIST 1.1
• Have an ECOG performance status of ≤1
• Must not be pregnant and/or planning to breastfeed during the trial or within 180 days of the last dose of trial intervention
• Must be able to swallow tablets
• Participants with asymptomatic or treated CNS disease may be eligible

Exclusion criteria

• Have known active CNS metastases and/or carcinomatous meningitis
• Have any unresolved toxicities from prior therapy greater than NCI CTCAE Version 5.0 Grade 1 at the time of starting trial treatment, except for alopecia, peripheral neuropathy and ongoing endocrinopathies controlled on appropriate replacement therapy
• Have significant cardiovascular disease defined as unstable angina or acute coronary syndrome, history of myocardial infarction, known left ventricular ejection fraction or heart failure, uncontrolled or symptomatic arrhythmias.
• Have known active hepatitis B virus (HBV), hepatitis C virus (HCV) and untreated HIV infection
• Have other active malignancy unless in remission with life expectancy greater than 2 years.
• Have active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
• Have history of non-infectious pneumonitis/interstitial lung disease that received steroids or has current clinically significant pneumonitis/interstitial lung disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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750 participants in 2 patient groups

LY4066434 Monotherapy Dose Escalation

Experimental group

Description:

Escalating doses of LY4066434 administered orally.

Treatment:

Drug: LY4066434.

LY4066434 Dose Optimization

Experimental group

Description:

LY4066434 administered orally either alone or with another investigational agent.

Treatment:

Drug: LY4066434.

Drug: Oxaliplatin

Drug: Cetuximab

Drug: Cisplatin

Drug: Carboplatin

Drug: 5Fluorouracil

Drug: Gemcitabine

Drug: Nab paclitaxel

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Irinotecan

Drug: Leucovorin