Clinical trial NCT06607185: A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors
Official title: A Phase 1a/1b Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Ductal Adenocarcinoma
Non-small Cell Lung Cancer
Colorectal Cancer
Advanced Solid Tumor
Metastatic Solid Tumor
Keywords: KRAS
KRAS mutation
KRASG12C
KRASG12D
KRASG12V
KRASG12S
KRASG12A
KRASG13D
LY4066434
Targeted therapy
Lung cancer
Pancreas cancer
Colon cancer
Rectal cancer
Colorectal cancer
Ovarian cancer
Endometrial cancer
Cholangiocarcinoma
Esophageal cancer
KRAS-mutant tumor
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-09-23
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Dose-limiting Toxicities (DLTs)
timeFrame: During the first cycle of LY4066434 treatment (up to 28 days)
measure: 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
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 5 years
measure: Best Overall Response (BOR)
timeFrame: Up to approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 5 years
measure: Time to Response (TTR)
timeFrame: Up to approximately 5 years
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 Alone
timeFrame: Predose through Day 168
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 in Combination With Other Agents
timeFrame: Predose through Day 168
measure: PK: Time to Maximum Concentration (Tmax) of LY4066434 Alone
timeFrame: Predose through Day 168
measure: PK: Time to Maximum Concentration (Tmax) of LY4066434 in Combination With Other Agents
timeFrame: Predose through Day 168
measure: PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 Alone
timeFrame: Predose through Day 168
measure: PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 in Combination With Other Agents
timeFrame: Predose through Day 168
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Chicago
country: United States
facility: The University of Chicago Medical Center (UCMC)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University (IU)
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: South Texas Accelerated Research Therapeutics (START) Midwest
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma - Health Sciences Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute (SCI)
state: Washington
city: Brussels
country: Belgium
facility: Universite Libre de Bruxelles (ULB) - Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Gent
country: Belgium
facility: University Hospital Gent
city: Beijing
country: China
facility: Cancer Institute & Hospital, Chinese Academy of Medical Sciences
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
city: Jinan
country: China
facility: Shandong Province Tumor Hospital
city: Shanghai
country: China
facility: Shanghai East Hospital, Tongji University
city: Lyon
country: France
facility: Centre Leon Berard
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest GmbH
city: Hamburg
country: Germany
facility: Asklepios Kliniken Hamburg GmbH - Asklepios Klinik Altona
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmBH
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona s.r.l.
city: Kashiwa, Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - L'Hospitalet
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Hsinchu
country: Taiwan
facility: National Taiwan University Hospital Hsin-Chu Branch
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: