A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer
A Phase 1 Study of an ERK1/2 Inhibitor (LY3214996) Administered Alone or in Combination With Other Agents in Advanced Cancer
3 other identifiers
interventional
210
4 countries
13
Brief Summary
The purpose of this study is to determine the safety of an extracellular signal regulated kinase (ERK1/2) inhibitor LY3214996 administered alone or in combination with other agents in participants with advanced cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2016
Longer than P75 for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 3, 2016
CompletedFirst Posted
Study publicly available on registry
August 5, 2016
CompletedStudy Start
First participant enrolled
September 29, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 10, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
October 24, 2022
CompletedNovember 22, 2022
November 1, 2022
4.4 years
August 3, 2016
November 21, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs)
Cycle 1 (21 Days)
Secondary Outcomes (13)
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of LY3214996 Administered as Monotherapy and when Administered in Combination with Nab-Paclitaxel Plus Gemcitabine, Abemaciclib and Encorafenib Plus Cetuximab
Cycle 1 Day 1 through Cycle 2 Day 1 (up to 28 Day Cycles)
PK: AUC of Gemcitabine when Administered with LY3214996
Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
PK: AUC of Nab-Paclitaxel when Administered with LY3214996
Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
PK: AUC of Abemaciclib and its Metabolites when Administered with LY3214996
Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
PK: AUC of Encorafenib when Administered with LY3214996
Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
- +8 more secondary outcomes
Study Arms (8)
LY3214996 Dose Escalation
EXPERIMENTALLY3214996 given orally once a day (or twice a day) for 21 days.
LY3214996 + Midazolam
EXPERIMENTAL(Preliminary Drug-Drug Interactions \[DDI\]) LY3214996 given orally (once a day) and midazolam given orally on cycle 1 day 1 and cycle 1 day 16 (21 day cycles except cycle 1 only = 22 days).
LY3214996 Dose Expansion
EXPERIMENTALLY3214996 given orally (once a day) during each 21 day cycle.
LY3214996 + Abemaciclib
EXPERIMENTALDose Escalation and Expansion- LY3214996 given orally (dose timing will be determined) and abemaciclib given orally (single dose given during lead in period) twice a day every 12 hours during 21 day cycle.
LY3214996 + Nab-Paclitaxel + Gemcitabine
EXPERIMENTALDose Escalation and Expansion- LY3214996 given orally (dose timing will be determined) and nab-paclitaxel given intravenously (IV) on day 1, 8, and 15 and gemcitabine IV on day 1, 8, and 15 during each 28 day cycle.
LY3214996 + Encorafenib + Cetuximab
EXPERIMENTALDose Escalation and Expansion- LY3214996 given orally, encorafenib given orally and cetuximab given IV.
Japan Part 1
EXPERIMENTALLY3214996 given orally.
Japan Part 2
EXPERIMENTALLY3214996 given orally and abemaciclib given orally.
Interventions
Administered orally
Eligibility Criteria
You may qualify if:
- Have advanced or metastatic cancer (solid tumors) and be an appropriate candidate for experimental therapy.
- Part B (No Longer Enrolling Participants): Have advanced or metastatic cancer with an activating mitogen-activated protein kinase pathway alteration, BRAF mutant metastatic melanoma refractory to or relapsed after treatment with RAF and/or MEK inhibitors, metastatic melanoma with a NRAS mutation, or BRAF mutant NSCLC.
- Part C: Advanced, unresectable cancer (dose escalation) and advanced, unresectable, or metastatic non-small cell lung cancer with a BRAF or RAS mutation, or NRAS mutant melanoma (dose expansion).
- Part D (No Longer Enrolling Participants): Have metastatic pancreatic ductal adenocarcinoma (dose escalation and dose expansion).
- Part E: Metastatic BRAF V600E colorectal cancer.
- Have adequate organ function.
- Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
You may not qualify if:
- Have serious preexisting medical conditions.
- Have a known human immunodeficiency virus (HIV) infection or known activated/reactivated hepatitis A, B, or C.
- Have symptomatic central nervous system malignancy or metastasis.
- Have current hematologic malignancies, acute or chronic leukemia.
- Have a second primary malignancy that in the judgment of the investigator or Lilly may affect the interpretation of results.
- Have prior malignancies. Participants with carcinoma in situ of any origin and participants with prior malignancies who are in remission and whose likelihood of recurrence is very low, as judged by the Lilly clinical research physician, are eligible for this study.
- Have a mean QT interval corrected for heart rate (QTc) of ≥470 milliseconds on screening electrocardiogram (ECG) as calculated using the Bazett's formula at several consecutive days of assessment.
- Have participated, within the last 28 days in a clinical trial involving an investigational product or are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
- Have previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor.
- If female, is pregnant, breastfeeding, or planning to become pregnant.
- Have history or findings of central or branch retinal artery or venous occlusion with significant vision loss or other retinal diseases that cause current visual impairment or would likely cause visual impairment over the time period of the study.
- Currently using concomitant medications that are strong inhibitors or inducers of CYP3A4.
- Part C: have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study, including interstitial lung disease (ILD) or severe dyspnea at rest or requiring oxygen therapy.
- Part C4 NRAS Melanoma: have previously completed or withdrawn from a study investigating a MEK inhibitor.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
Florida Cancer Specialists
Sarasota, Florida, 34232, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0001, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232-1305, United States
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203, United States
Tennessee Oncology PLLC
Nashville, Tennessee, 37203, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
St Vincent's Hospital
Sydney, New South Wales, 2010, Australia
Linear Clinical Research Ltd
Nedlands, Western Australia, 6009, Australia
Gustave Roussy
Villejuif, 94805, France
Shizuoka Cancer Center
Sunto-Gun, Shizuoka, 411-8777, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045, Japan
Related Publications (1)
Bhagwat SV, McMillen WT, Cai S, Zhao B, Whitesell M, Shen W, Kindler L, Flack RS, Wu W, Anderson B, Zhai Y, Yuan XJ, Pogue M, Van Horn RD, Rao X, McCann D, Dropsey AJ, Manro J, Walgren J, Yuen E, Rodriguez MJ, Plowman GD, Tiu RV, Joseph S, Peng SB. ERK Inhibitor LY3214996 Targets ERK Pathway-Driven Cancers: A Therapeutic Approach Toward Precision Medicine. Mol Cancer Ther. 2020 Feb;19(2):325-336. doi: 10.1158/1535-7163.MCT-19-0183. Epub 2019 Nov 19.
PMID: 31744895DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
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)
Eli Lilly and Company
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 3, 2016
First Posted
August 5, 2016
Study Start
September 29, 2016
Primary Completion
February 10, 2021
Study Completion
October 24, 2022
Last Updated
November 22, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will not share