Pancreatic Ductal AdenocarcinomaPhase 1NCT06607185
A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors
A Phase 1 study testing LY4066434., Cetuximab and Nab paclitaxel in people with Pancreatic Ductal Adenocarcinoma and Non-small Cell Lung Cancer, run by Eli Lilly and Company at 45 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Ductal Adenocarcinoma, Non-small Cell Lung Cancer, Colorectal Cancer
- What is being tested?
- LY4066434., Cetuximab and Nab paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 750 participants
- Where
- 45 sitesin 8 countries
- Study dates
- 21 Oct 2024to Jan 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
45 sites in 8 countries.
45 sites in 8 countries
United States22 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The University of Chicago Medical Center (UCMC)
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
University of Texas Southwestern
Dallas, Texas, 75244
City of Hope
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Virginia Cancer Specialists
Fairfax, Virginia, 22031
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, 49546
MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University (IU)
Indianapolis, Indiana, 46202
Sarah Cannon Research Institute/SCRI
Nashville, Tennessee, 37203
SCRI Oncology Partners
Nashville, Tennessee, 37203
Yale University School of Medicine - Yale Cancer Center
New Haven, Connecticut, 06520-8028
Columbia University
New York, New York, 10032
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mayo Clinic
Phoenix, Arizona, 85054
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229
University of California, Los Angeles (UCLA)
Santa Monica, California, 90404
Swedish Cancer Institute (SCI)
Seattle, Washington, 98104
Spain7 sites
Hospital del Mar
Barcelona, 08003
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Institut Catala d'Oncologia - L'Hospitalet
Barcelona, 08908
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Regional Universitario de Malaga
Málaga, 29010
Japan5 sites
National Cancer Center Hospital East
Chiba, 277-8577
Kyoto University Hospital
Kyoto, 606-8507
Shizuoka Cancer Center
Shizuoka, 411-8777
National Cancer Center Hospital
Tokyo, 104-0045
Cancer Institute Hospital of JFCR
Tokyo, 135-8550
Germany4 sites
Krankenhaus Nordwest GmbH
Frankfurt, 60488
Asklepios Kliniken Hamburg GmbH - Asklepios Klinik Altona
Hamburg, 22763
SLK-Kliniken Heilbronn GmBH
Heilbronn, 74078
Universitaetsklinikum Wuerzburg
Würzburg, 97080
Belgium3 sites
Universite Libre de Bruxelles (ULB) - Institut Jules Bordet
Brussels, 1070
Cliniques universitaires Saint-Luc
Brussels, 1200
UZ Gent
Ghent, 9000
Taiwan2 sites
National Taiwan University Hospital Hsin-Chu Branch
Hsinchu, 300195
National Taiwan University Hospital
Taipei, 10016
About this study
Official title: A Phase 1a/1b 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.
- Conditions
- Pancreatic Ductal Adenocarcinoma, Non-small Cell Lung Cancer, Colorectal Cancer, Advanced Solid Tumor, Metastatic Solid Tumor
- Being tested
- LY4066434., Cetuximab, Nab paclitaxel, Gemcitabine, Oxaliplatin
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Neoplasm Metastasis, Lung Neoplasms, Pancreatic Neoplasms, Colonic Neoplasms, Rectal Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY4066434.Drug
Administered orally.
CetuximabDrug
Administered intravenously.
Nab paclitaxelDrug
Administered intravenously.
GemcitabineDrug
Administered intravenously.
OxaliplatinDrug
Administered intravenously.
LeucovorinDrug
Also called Folinic Acid
Administered intravenously.
IrinotecanDrug
Administered intravenously.
5FluorouracilDrug
Administered intravenously.
CarboplatinDrug
Administered intravenously.
CisplatinDrug
Administered intravenously.
PemetrexedDrug
Administered intravenously.
PembrolizumabDrug
Administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| LY4066434 Monotherapy Dose Escalation | Experimental | Escalating doses of LY4066434 administered orally. Receives: Drug: LY4066434. |
| LY4066434 Dose Optimization | Experimental | LY4066434 administered orally either alone or with another investigational agent. Receives: Drug: LY4066434.; Drug: Cetuximab; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: 5Fluorouracil; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Dose-limiting Toxicities (DLTs)
Measured: During the first cycle of LY4066434 treatment (up to 28 days)
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
A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.
Measured: Up to approximately 5 years
Secondary outcomes (11)
Overall Response Rate (ORR)
ORR as assessed by investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
Measured: Up to approximately 5 years
Best Overall Response (BOR)
BOR as assessed by investigator per RECIST v1.1
Measured: Up to approximately 5 years
Duration of Response (DOR)
DOR as assessed by investigator per RECIST v1.1
Measured: Up to approximately 5 years
Disease Control Rate (DCR)
DCR as assessed by investigator per RECIST v1.1
Measured: Up to approximately 5 years
Time to Response (TTR)
TTR as assessed by investigator per RECIST v1.1
Measured: Up to approximately 5 years
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 Alone
PK: Cmax of LY4066434
Measured: Predose through Day 168
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 in Combination With Other Agents
PK: Cmax of LY4066434
Measured: Predose through Day 168
PK: Time to Maximum Concentration (Tmax) of LY4066434 Alone
PK: Tmax of LY4066434
Measured: Predose through Day 168
PK: Time to Maximum Concentration (Tmax) of LY4066434 in Combination With Other Agents
PK: Tmax of LY4066434
Measured: Predose through Day 168
PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 Alone
PK: AUC of LY4066434
Measured: Predose through Day 168
PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 in Combination With Other Agents
PK: AUC of LY4066434
Measured: Predose through Day 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2024
- Study start21 Oct 2024
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 750 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06607185
- Sponsor's protocol ID
- 27237
- Other IDs
- J5Q-OX-JRDA
- Status last verified
- Jul 2026
- First submitted
- 19 Sep 2024
- Last updated
- 20 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No