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Active, Not Recruiting

NCT Number: NCT06607185

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Pancreatic Ductal Adenocarcinoma Adenocarcinoma Adnexal Diseases Advanced Solid Tumor Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Cholangiocarcinoma Colonic Diseases Colonic Neoplasms Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Esophageal Diseases Esophageal Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Metastatic Solid Tumor Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplastic Processes Non-small Cell Lung Cancer Ovarian Diseases Ovarian Neoplasms Pancreatic Diseases Pancreatic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Rectal Diseases Rectal Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cliniques universitaires Saint-Luc, Brussels, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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, hearing loss, 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) or 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

Treatment and study plan

LY4066434.

Drug

Administered orally.

Cetuximab

Drug

Administered intravenously.

Nab paclitaxel

Drug

Administered intravenously.

Gemcitabine

Drug

Administered intravenously.

Oxaliplatin

Drug

Administered intravenously.

Leucovorin

Drug

Administered intravenously.

Other names: Folinic Acid

Irinotecan

Drug

Administered intravenously.

5Fluorouracil

Drug

Administered intravenously.

carboplatin

Drug

Administered intravenously.

Cisplatin

Drug

Administered intravenously.

Pemetrexed

Drug

Administered intravenously.

Pembrolizumab

Drug

Administered intravenously.

Primary outcomes

  1. Number of Participants with Dose-limiting Toxicities (DLTs)

    Time frame: During the first cycle of LY4066434 treatment (up to 28 days)

  2. Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

    Time frame: Up to approximately 5 years

    A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.

Secondary outcomes

  1. Overall Response Rate (ORR)

    Time frame: Up to approximately 5 years

    ORR as assessed by investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)

  2. Best Overall Response (BOR)

    Time frame: Up to approximately 5 years

    BOR as assessed by investigator per RECIST v1.1

  3. Duration of Response (DOR)

    Time frame: Up to approximately 5 years

    DOR as assessed by investigator per RECIST v1.1

  4. Disease Control Rate (DCR)

    Time frame: Up to approximately 5 years

    DCR as assessed by investigator per RECIST v1.1

  5. Time to Response (TTR)

    Time frame: Up to approximately 5 years

    TTR as assessed by investigator per RECIST v1.1

  6. Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 Alone

    Time frame: Predose through Day 168

    PK: Cmax of LY4066434

  7. Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 in Combination With Other Agents

    Time frame: Predose through Day 168

    PK: Cmax of LY4066434

  8. PK: Time to Maximum Concentration (Tmax) of LY4066434 Alone

    Time frame: Predose through Day 168

    PK: Tmax of LY4066434

  9. PK: Time to Maximum Concentration (Tmax) of LY4066434 in Combination With Other Agents

    Time frame: Predose through Day 168

    PK: Tmax of LY4066434

  10. PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 Alone

    Time frame: Predose through Day 168

    PK: AUC of LY4066434

  11. PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 in Combination With Other Agents

    Time frame: Predose through Day 168

    PK: AUC of LY4066434

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Phase 1a/1b Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors

Important dates

Study start
2024
Primary completion
2030
Study completion
2030
First posted
Sep 23, 2024
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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