A Phase Ia/Ib Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors
Study Identifier:
J5Q-OX-JRDA
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruitment Complete
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Study Summary
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. To study oral LY4066434 in participants (pts) with KRAS-mutant solid tumors. It is conducted in 2 phases: monotherapy dose escalation (Part A) to evaluate LY4066434 monotherapy and randomized dose optimization (Parts B-E) to evaluate LY4066434 monotherapy and in combination with other anticancer therapies. Key objectives are to determine the optimal dose and assess the safety, PK properties, and antitumor activity of LY4066434 per RECIST v1.1.
Primary objective: To evaluate the safety and tolerability of LY4066434 monotherapy.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I
Sex
Female & Male
Age
18+ years
Study Drug
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
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 Eligible pts (≥18 years) must have locally advanced, unresectable, and/or metastatic cancer, measurable disease per RECIST v1.1, evidence of KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumors or ctDNA, and an ECOG PS of ≤1; asymptomatic CNS disease is allowed. In Part A, pts must have received ≥1 prior systemic therapy;
- CFDA:
- 1There must be sufficient organ function, as defined in the protocol:2According to RECIST 1.1, the presence of measurable lesions was determined.3ECOG Performance Status Score ≤14Pregnancy and/or planned breastfeeding are prohibited during the study period or within 180 days after the last dose of study treatment.5Must be able to swallow tablets6Applicants must be 18 years of age or older at the time of selection, or of legal adult age as required by local regulations (whichever is higher).7A diagnosis of locally advanced, unresectable, and/or metastatic solid tumor cancer confirmed by histology or cytology. The disease must be unsuitable for radical surgery or radiation therapy.8In dose optimization, the subject must be diagnosed with: Part B: PDAC; Part C: CRC; Part D: NSCLC; Part E: other solid tumors.9Subjects should only be enrolled if the investigator determines that they are suitable for the planned treatment regimen specified in the protocol. Subjects who have previously received no more than one cycle of treatment are considered untreated. Subjects are ineligible if dose adjustment is required or DLT-equivalent toxicity is observed.10Women of childbearing age must agree to use a highly effective method of contraception during the study treatment and for at least 6 months after the last dose of the study treatment.11Women of childbearing age must have a negative serum pregnancy test within 14 days prior to the start of treatment. If a serum pregnancy test is obtained more than 7 days before C1D1, a negative urine pregnancy test result must be obtained at C1D1.12Participants must be able to understand the nature, significance, and impact of participating in the study and sign an informed consent form as described in Section 10.3, which includes requirements and limitations for compliance with the ICF and this protocol.13During participation in the study, participants must be able to adhere to outpatient treatment, laboratory monitoring, and required outpatient visits.
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 Key exclusion criteria include other driver alterations or prior KRAS inhibitor treatment (a limited number of pts may be enrolled in backfill with sponsor approval).
- CFDA:
- 1Known active CNS metastases and/or carcinomatous meningitis2Known active HBV infection3At the start of the study, any unrelieved toxicity exceeding NCI CTCAE (version 5.0) grade 1 caused by prior treatment was present, except for alopecia, hearing loss, peripheral neuropathy, and persistent endocrine disorders controlled by appropriate alternative therapy.4Severe cardiovascular disease, such as any of those defined in the protocol:5A history of non-infectious pneumonia/ILD treated with steroids or current clinically significant pneumonia/ILD.6The corrected QTcF during screening was extended to >470 ms. If the ECG results obtained during screening showed QTcF >470 ms, the ECG check was repeated twice, and the average of the three results was calculated to assess study eligibility.7Active, uncontrolled systemic bacterial, viral, fungal, or parasitic infections (excluding fungal nail infections), or other clinically significant active diseases that the investigator and sponsor deem inadvisable for participant participation in the study. Screening for chronic diseases is not required.8Clinically significant active malabsorption syndrome or other conditions that may affect the gastrointestinal absorption of the investigational drug when administered orally.9Researchers determined that a clinically significant active or gastrointestinal disease history (including but not limited to ulcerative colitis, Crohn's disease, inflammatory bowel disease, immune-mediated colitis, peptic ulcer, gastrointestinal bleeding, and chronic diarrhea) would prevent a participant from participating in the study.10Other active malignant tumors, unless the condition is in remission and the life expectancy is >2 years.11History of allogeneic tissue/solid organ transplantation or allogeneic stem cell transplantation.12Previously received KRAS inhibitors targeting any KRAS mutant.13Hypersensitivity is known to occur to any component or excipient in any investigational treatment.14Known active HCV infection15Known untreated HIV infection
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Nehal Lakhani
Status
Recruiting
Condition(s) Treated at Site
Pancreas
Non-Small Cell Lung Cancer
Bowel (Colorectal)
Solid Tumor
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Amita Patnaik
Status
Recruiting
Condition(s) Treated at Site
Pancreas
Non-Small Cell Lung Cancer
Bowel (Colorectal)
Solid Tumor