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

Colorectal Cancer Clinical Trial

Official title:

A Phase 1 Study of an ERK1/2 Inhibitor (LY3214996) Administered Alone or in Combination With Other Agents in Advanced Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02857270
• Other study ID #: 16419
• Secondary ID: I8S-MC-JUAB2016-
• Status: Completed
• Phase: Phase 1
• Start date: September 29, 2016
• Est. completion date: October 24, 2022

Study information

• Verified date: November 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: October 24, 2022
• Est. primary completion date: February 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 discontinued previous treatments for cancer and have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy to Grade =1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.
• 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.

Related Conditions & MeSH terms

• Advanced Cancer
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Melanoma
• Metastatic Non-small Cell Lung Cancer

Intervention

Drug:
• LY3214996
Administered orally
• Midazolam
Administered orally
• Abemaciclib
Administered orally
• Nab-paclitaxel
Administered IV
• Gemcitabine
Administered IV
• Encorafenib
Administered orally
• Cetuximab
Administered IV

Locations

Country	Name	City	State
Australia	Linear Clinical Research Ltd	Nedlands	Western Australia
Australia	St Vincent's Hospital	Sydney	New South Wales
France	Gustave Roussy	Villejuif Cedex
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Shizuoka Cancer Center	Sunto-Gun	Shizuoka
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  France,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs)		Cycle 1 (21 Days)
Secondary	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)
Secondary	PK: AUC of Gemcitabine when Administered with LY3214996		Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
Secondary	PK: AUC of Nab-Paclitaxel when Administered with LY3214996		Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
Secondary	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)
Secondary	PK: AUC of Encorafenib when Administered with LY3214996		Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
Secondary	PK: AUC of Cetuximab when Administered with LY3214996		Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
Secondary	PK: AUC of Midazolam and its 1'-Hydroxymidazolam Metabolite when Administered Alone and in Combination with LY3214996		Cycle 1 Day 1 through Cycle 1 Day 16 (21 Day Cycles)
Secondary	Objective Response Rate (ORR): Percentage of Participants With a Complete (CR) or Partial Response (PR)		Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 6 Months)
Secondary	Duration of Response (DoR)		Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 12 Months)
Secondary	Time to First Response (TTR)		Baseline to Date of CR or PR (Estimated up to 6 Months)
Secondary	Progression Free Survival (PFS)		Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months)
Secondary	Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR		Baseline through Measured Progressive Disease (Estimated up to 6 Months)
Secondary	Overall Survival (OS) (Dose Expansion Arms Only)		Baseline to Date of Death from Any Cause (Estimated up to 2 Years)

External Links

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