Clinical Trial - NCT02857270

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

Recruiting

Sponsor: Eli Lilly and Company

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02857270

Protocol Info

Short Description: Phase I LY3214996 With or Without Other Agents in Advanced Cancer
Long Description: A Phase 1 Study of an ERK1/2 Inhibitor (LY3214996) Administered Alone or in Combination with Other Agents in Advanced Cancer
MGH Status: Open
Sponsor: Eli Lilly
Disease Program: Phase I

Next Steps


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Purpose

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.
Condition Title Intervention Phase
Advanced Cancer Metastatic Melanoma Metastatic Non-small Cell Lung Cancer Metastatic Pancreatic Ductal Adenocarcinoma Colorectal Cancer LY3214996 Midazolam Abemaciclib Nab-paclitaxel Gemcitabine Encorafenib Cetuximab Phase 1
Study Type Interventional
Official Title A Phase 1 Study of an ERK1/2 Inhibitor (LY3214996) Administered Alone or in Combination With Other Agents in Advanced Cancer

Primary Outcome Measures

Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs) [Time Frame: Cycle 1 (21 Days)] [Designated as safety issue: ]


Secondary Outcome Measures

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 Cetuximanb [Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 28 Day Cycles)] [Designated as safety issue: ]

PK: AUC of Gemcitabine when Administered with LY3214996 [Time Frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)] [Designated as safety issue: ]

PK: AUC of Nab-Paclitaxel when Administered with LY3214996 [Time Frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)] [Designated as safety issue: ]

PK: AUC of Abemaciclib and its Metabolites when Administered with LY3214996 [Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)] [Designated as safety issue: ]

PK: AUC of Encorafenib when Administered with LY3214996 [Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)] [Designated as safety issue: ]

PK: AUC of Cetuximab when Administered with LY3214996 [Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)] [Designated as safety issue: ]

PK: AUC of Midazolam and its 1'-Hydroxymidazolam Metabolite when Administered Alone and in Combination with LY3214996 [Time Frame: Cycle 1 Day 1 through Cycle 1 Day 16 (21 Day Cycles)] [Designated as safety issue: ]

Objective Response Rate (ORR): Percentage of Participants With a Complete (CR) or Partial Response (PR) [Time Frame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 6 Months)] [Designated as safety issue: ]

Duration of Response (DoR) [Time Frame: 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)] [Designated as safety issue: ]

Time to First Response (TTR) [Time Frame: Baseline to Date of CR or PR (Estimated up to 6 Months)] [Designated as safety issue: ]

Progression Free Survival (PFS) [Time Frame: Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months)] [Designated as safety issue: ]

Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR [Time Frame: Baseline through Measured Progressive Disease (Estimated up to 6 Months)] [Designated as safety issue: ]

Overall Survival (OS) (Dose Expansion Arms Only) [Time Frame: Baseline to Date of Death from Any Cause (Estimated up to 2 Years)] [Designated as safety issue: ]

Estimated Enrollment: 272
Study Start Date: September 2016
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2021
Arms Assigned Interventions

Experimental:LY3214996 Dose Escalation

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

Experimental:LY3214996 + Midazolam

(Preliminary Drug-Drug Interactions [DDI]) LY3214996 given orally (dose timing will be determined) and midazolam given orally on cycle 1 day 1 and cycle 1 day 16 (21 day cycles except cycle 1 only = 22 days).
Drug:Midazolam
Administered orally

Experimental:LY3214996 Monotherapy

LY3214996 given orally (dose timing will be determined) during each 21 day cycle.

Experimental: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.
Drug:Abemaciclib
Administered orally

Experimental: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.
Drug:Gemcitabine
Administered IV

Experimental:LY3214996 + Encorafenib + Cetuximab

Dose Escalation and Expansion- LY3214996 given orally, encorafenib given orally and cetuximab given IV.
Drug:Cetuximab
Administered IV

Experimental:Japan Part 1

LY3214996 given orally.

Experimental:Japan Part 2

LY3214996 given orally and abemaciclib given orally.

Experimental:Japan Part 3

LY3214996 given orally, nab-paclitaxel given IV and gemcitabine IV.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Have advanced or metastatic cancer (solid tumors) and be an appropriate candidate for experimental therapy.
  • Part B: 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 an NRAS mutation, 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, and colorectal cancer with a RAS mutation and advanced or metastatic cancer with an activating mitogen activated protein kinase pathway alteration (dose expansion).
  • Part D: Have metastatic pancreatic ductal adenocarcinoma (dose escalation and dose expansion).
  • Part E: Metastatic BRAF V600E colorectal cancer (dose escalation and dose expansion).
  • 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02857270

Locations

  • United States, District of Columbia
    • Georgetown University Medical Center Washington, District of Columbia, United States, 20007
  • United States, Florida
    • Florida Cancer Specialists Sarasota, Florida, United States, 34232
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, New Hampshire
    • Dartmouth Hitchcock Medical Center Lebanon, New Hampshire, United States, 03756-0001
  • United States, Pennsylvania
    • UPMC Hillman Cancer Center Pittsburgh, Pennsylvania, United States, 15232-1305
  • United States, Tennessee
    • Sarah Cannon Cancer Center Nashville, Tennessee, United States, 37203
    • Tennessee Oncology PLLC Nashville, Tennessee, United States, 37203
  • United States, Texas
    • University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030
  • Australia, New South Wales
    • St Vincent's Hospital Sydney, New South Wales, Australia, 2010
  • Australia, Western Australia
    • Linear Clinical Research Ltd Nedlands, Western Australia, Australia, 6009
  • France,
    • Gustave Roussy Villejuif Cedex, , France, 94805
  • Japan, Shizuoka
    • Shizuoka Cancer Center Sunto-Gun, Shizuoka, Japan, 411-8777
  • Japan, Tokyo
    • National Cancer Center Hospital Chuo-Ku, Tokyo, Japan, 104-0045

Sponsors and Collaborators

Eli Lilly and Company

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02857270
Other Study ID Numbers: I8S-MC-JUAB
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Eli Lilly and Company:

MAPK

RAS

BRAF

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Colorectal Neoplasms

Adenocarcinoma

Paclitaxel

Albumin-Bound Paclitaxel

Gemcitabine

Cetuximab

Midazolam

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019