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Trial record 4 of 6 for:    LY3214996

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02857270
Recruitment Status : Recruiting
First Posted : August 5, 2016
Last Update Posted : July 28, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE August 3, 2016
First Posted Date  ICMJE August 5, 2016
Last Update Posted Date July 28, 2020
Actual Study Start Date  ICMJE September 29, 2016
Estimated Primary Completion Date December 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2016)
Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (21 Days) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2020)
  • 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 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 28 Day Cycles) ]
  • PK: AUC of Gemcitabine when Administered with LY3214996 [ Time Frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles) ]
  • PK: AUC of Nab-Paclitaxel when Administered with LY3214996 [ Time Frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles) ]
  • 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) ]
  • PK: AUC of Encorafenib when Administered with LY3214996 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles) ]
  • PK: AUC of Cetuximab when Administered with LY3214996 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Time to First Response (TTR) [ Time Frame: Baseline to Date of CR or PR (Estimated up to 6 Months) ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months) ]
  • 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) ]
  • Overall Survival (OS) (Dose Expansion Arms Only) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated up to 2 Years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2016)
  • Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of LY3214996 Administered as Monotherapy and when Administered in Combination with Nab-Paclitaxel Plus Gemcitabine, and Abemaciclib [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 28 Day Cycles) ]
  • PK: AUC of Gemcitabine when Administered with LY3214996 [ Time Frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles) ]
  • PK: AUC of Nab-Paclitaxel when Administered with LY3214996 [ Time Frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Time to First Response (TTR) [ Time Frame: Baseline to Date of CR or PR (Estimated up to 6 Months) ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer
Official Title  ICMJE A Phase 1 Study of an ERK1/2 Inhibitor (LY3214996) Administered Alone or in Combination With Other Agents in Advanced Cancer
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Cancer
  • Metastatic Melanoma
  • Metastatic Non-small Cell Lung Cancer
  • Colorectal Cancer
Intervention  ICMJE
  • Drug: LY3214996
    Administered orally
  • Drug: Midazolam
    Administered orally
  • Drug: Abemaciclib
    Administered orally
    Other Name: LY2835219
  • Drug: Nab-paclitaxel
    Administered IV
  • Drug: Gemcitabine
    Administered IV
  • Drug: Encorafenib
    Administered orally
  • Drug: Cetuximab
    Administered IV
Study Arms  ICMJE
  • Experimental: LY3214996 Dose Escalation
    LY3214996 given orally once a day (or twice a day) for 21 days.
    Intervention: Drug: LY3214996
  • Experimental: 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).

    Interventions:
    • Drug: LY3214996
    • Drug: Midazolam
  • Experimental: LY3214996 Dose Expansion
    LY3214996 given orally (once a day) during each 21 day cycle.
    Intervention: Drug: LY3214996
  • 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.
    Interventions:
    • Drug: LY3214996
    • Drug: Abemaciclib
  • 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.
    Interventions:
    • Drug: LY3214996
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
  • Experimental: LY3214996 + Encorafenib + Cetuximab
    Dose Escalation and Expansion- LY3214996 given orally, encorafenib given orally and cetuximab given IV.
    Interventions:
    • Drug: LY3214996
    • Drug: Encorafenib
    • Drug: Cetuximab
  • Experimental: Japan Part 1
    LY3214996 given orally.
    Intervention: Drug: LY3214996
  • Experimental: Japan Part 2
    LY3214996 given orally and abemaciclib given orally.
    Interventions:
    • Drug: LY3214996
    • Drug: Abemaciclib
  • Experimental: Japan Part 3
    LY3214996 given orally, nab-paclitaxel given IV and gemcitabine IV.
    Interventions:
    • Drug: LY3214996
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 24, 2020)
245
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2016)
136
Estimated Study Completion Date  ICMJE December 15, 2021
Estimated Primary Completion Date December 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559
Listed Location Countries  ICMJE Australia,   France,   Japan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02857270
Other Study ID Numbers  ICMJE 16419
I8S-MC-JUAB ( Other Identifier: Eli Lilly and Company )
2016-001907-21 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date July 1, 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP