Clinical Trials /

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

NCT02857270

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

  • ORG STUDY ID: 16419
  • SECONDARY ID: I8S-MC-JUAB
  • SECONDARY ID: 2016-001907-21
  • NCT ID: NCT02857270

Conditions

  • Advanced Cancer
  • Metastatic Melanoma
  • Metastatic Non-small Cell Lung Cancer
  • Metastatic Pancreatic Ductal Adenocarcinoma
  • Colorectal Cancer

Interventions

DrugSynonymsArms
LY3214996LY3214996 Dose Escalation
MidazolamLY3214996 + Midazolam
AbemaciclibLY2835219LY3214996 + Abemaciclib
Nab-paclitaxelLY3214996 + Nab-Paclitaxel + Gemcitabine
GemcitabineLY3214996 + Nab-Paclitaxel + Gemcitabine
EncorafenibLY3214996 + Encorafenib + Cetuximab
CetuximabLY3214996 + Encorafenib + Cetuximab

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.

Trial Arms

NameTypeDescriptionInterventions
LY3214996 Dose EscalationExperimentalLY3214996 given orally once a day (or twice a day) for 21 days.
  • LY3214996
LY3214996 + MidazolamExperimental(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).
  • LY3214996
  • Midazolam
LY3214996 MonotherapyExperimentalLY3214996 given orally (dose timing will be determined) during each 21 day cycle.
  • LY3214996
LY3214996 + AbemaciclibExperimentalDose 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
  • Abemaciclib
LY3214996 + Nab-Paclitaxel + GemcitabineExperimentalDose 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
  • Nab-paclitaxel
  • Gemcitabine
LY3214996 + Encorafenib + CetuximabExperimentalDose Escalation and Expansion- LY3214996 given orally, encorafenib given orally and cetuximab given IV.
  • LY3214996
  • Encorafenib
  • Cetuximab
Japan Part 1ExperimentalLY3214996 given orally.
  • LY3214996
Japan Part 2ExperimentalLY3214996 given orally and abemaciclib given orally.
  • LY3214996
  • Abemaciclib
Japan Part 3ExperimentalLY3214996 given orally, nab-paclitaxel given IV and gemcitabine IV.
  • LY3214996
  • Nab-paclitaxel
  • Gemcitabine

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs)
Time Frame:Cycle 1 (21 Days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure:PK: AUC of Gemcitabine when Administered with LY3214996
Time Frame:Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
Safety Issue:
Description:
Measure:PK: AUC of Nab-Paclitaxel when Administered with LY3214996
Time Frame:Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:PK: AUC of Encorafenib when Administered with LY3214996
Time Frame:Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
Safety Issue:
Description:
Measure:PK: AUC of Cetuximab when Administered with LY3214996
Time Frame:Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Time to First Response (TTR)
Time Frame:Baseline to Date of CR or PR (Estimated up to 6 Months)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Overall Survival (OS) (Dose Expansion Arms Only)
Time Frame:Baseline to Date of Death from Any Cause (Estimated up to 2 Years)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • MAPK
  • RAS
  • BRAF

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