A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer

NCT ID: NCT02857270

Last Updated: 2022-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-29

Study Completion Date

2022-10-24

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Advanced Cancer Metastatic Melanoma Metastatic Non-small Cell Lung Cancer Colorectal Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

LY3214996 Dose Escalation

LY3214996 given orally once a day (or twice a day) for 21 days.

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

LY3214996 + Midazolam

(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).

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

Midazolam

Intervention Type DRUG

Administered orally

LY3214996 Dose Expansion

LY3214996 given orally (once a day) during each 21 day cycle.

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

LY3214996 + Abemaciclib

Dose 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.

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

Abemaciclib

Intervention Type DRUG

Administered orally

LY3214996 + Nab-Paclitaxel + Gemcitabine

Dose 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.

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

Nab-paclitaxel

Intervention Type DRUG

Administered IV

Gemcitabine

Intervention Type DRUG

Administered IV

LY3214996 + Encorafenib + Cetuximab

Dose Escalation and Expansion- LY3214996 given orally, encorafenib given orally and cetuximab given IV.

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

Encorafenib

Intervention Type DRUG

Administered orally

Cetuximab

Intervention Type DRUG

Administered IV

Japan Part 1

LY3214996 given orally.

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

Japan Part 2

LY3214996 given orally and abemaciclib given orally.

Group Type EXPERIMENTAL

LY3214996

Intervention Type DRUG

Administered orally

Abemaciclib

Intervention Type DRUG

Administered orally

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

LY3214996

Administered orally

Intervention Type DRUG

Midazolam

Administered orally

Intervention Type DRUG

Abemaciclib

Administered orally

Intervention Type DRUG

Nab-paclitaxel

Administered IV

Intervention Type DRUG

Gemcitabine

Administered IV

Intervention Type DRUG

Encorafenib

Administered orally

Intervention Type DRUG

Cetuximab

Administered IV

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

LY2835219

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

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

Eli Lilly and Company

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Site Status

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

St Vincent's Hospital

Sydney, New South Wales, Australia

Site Status

Linear Clinical Research Ltd

Nedlands, Western Australia, Australia

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Shizuoka Cancer Center

Sunto-Gun, Shizuoka, Japan

Site Status

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia France Japan

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 31744895 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://trials.lillytrialguide.com/en-US/trial/64K6fy9q0Mw2eU8WyW2u4K

A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

I8S-MC-JUAB

Identifier Type: OTHER

Identifier Source: secondary_id

2016-001907-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16419

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

A Study of LY2801653 in Advanced Cancer
NCT01285037 COMPLETED PHASE1
PhII ICb With/Without Erbitux in MBC Pts
NCT00248287 ACTIVE_NOT_RECRUITING PHASE2