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

Purpose

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.

Conditions

  • Pancreatic Ductal Adenocarcinoma
  • Non-small Cell Lung Cancer
  • Colorectal Cancer
  • Advanced Solid Tumor
  • Metastatic Solid Tumor

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
LY4066434 Monotherapy Dose Escalation 		Escalating doses of LY4066434 administered orally.
  • Drug: LY4066434.
    Administered orally.
Experimental
LY4066434 Dose Optimization 		LY4066434 administered orally either alone or with another investigational agent.
  • Drug: LY4066434.
    Administered orally.
  • Drug: Cetuximab
    Administered intravenously.
  • Drug: Nab paclitaxel
    Administered intravenously.
  • Drug: Gemcitabine
    Administered intravenously.
  • Drug: Oxaliplatin
    Administered intravenously.
  • Drug: Leucovorin
    Administered intravenously.
  • Drug: Irinotecan
    Administered intravenously.
  • Drug: 5Fluorouracil
    Administered intravenously.
  • Drug: Carboplatin
    Administered intravenously.
  • Drug: Cisplatin
    Administered intravenously.
  • Drug: Pemetrexed
    Administered intravenously.
  • Drug: Pembrolizumab
    Administered intravenously.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35233

More Details

Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
13176154559
clinical_inquiry_hub@lilly.com