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Advanced CancerPhase 1NCT02857270

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

A Phase 1 study testing LY3214996, Midazolam and Abemaciclib in people with Advanced Cancer and Metastatic Melanoma, run by Eli Lilly and Company at 13 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LY3214996, Midazolam and Abemaciclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
13 sitesin 4 countries
Study dates
29 Sep 2016to 24 Oct 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

United States8 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0001

  • Sarah Cannon Cancer Center

    Nashville, Tennessee, 37203

  • Tennessee Oncology PLLC

    Nashville, Tennessee, 37203

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232-1305

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

Australia2 sites

  • Linear Clinical Research Ltd

    Nedlands, Western Australia, 6009

  • St Vincent's Hospital

    Sydney, New South Wales, 2010

Other trials in Australia

Japan2 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • Shizuoka Cancer Center

    Sunto-Gun, Shizuoka, 411-8777

Other trials in Japan

France1 site

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

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

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.

Keywords
MAPK, RAS, BRAF
Medical subject headings
Melanoma, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02857270
Study groupRoleWhat they receive
LY3214996 Dose EscalationExperimentalLY3214996 given orally once a day (or twice a day) for 21 days.
Receives: Drug: LY3214996
LY3214996 + MidazolamExperimental(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).
Receives: Drug: LY3214996; Drug: Midazolam
LY3214996 Dose ExpansionExperimentalLY3214996 given orally (once a day) during each 21 day cycle.
Receives: Drug: 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.
Receives: Drug: LY3214996; Drug: 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.
Receives: Drug: LY3214996; Drug: Nab-paclitaxel; Drug: Gemcitabine
LY3214996 + Encorafenib + CetuximabExperimentalDose Escalation and Expansion- LY3214996 given orally, encorafenib given orally and cetuximab given IV.
Receives: Drug: LY3214996; Drug: Encorafenib; Drug: Cetuximab
Japan Part 1ExperimentalLY3214996 given orally.
Receives: Drug: LY3214996
Japan Part 2ExperimentalLY3214996 given orally and abemaciclib given orally.
Receives: Drug: LY3214996; Drug: Abemaciclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs)

    Measured: Cycle 1 (21 Days)

Secondary outcomes (13)

  1. 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

    Measured: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 28 Day Cycles)

  2. PK: AUC of Gemcitabine when Administered with LY3214996

    Measured: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)

  3. PK: AUC of Nab-Paclitaxel when Administered with LY3214996

    Measured: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)

  4. PK: AUC of Abemaciclib and its Metabolites when Administered with LY3214996

    Measured: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)

  5. PK: AUC of Encorafenib when Administered with LY3214996

    Measured: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)

  6. PK: AUC of Cetuximab when Administered with LY3214996

    Measured: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)

  7. PK: AUC of Midazolam and its 1'-Hydroxymidazolam Metabolite when Administered Alone and in Combination with LY3214996

    Measured: Cycle 1 Day 1 through Cycle 1 Day 16 (21 Day Cycles)

  8. Objective Response Rate (ORR): Percentage of Participants With a Complete (CR) or Partial Response (PR)

    Measured: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 6 Months)

  9. Duration of Response (DoR)

    Measured: 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)

  10. Time to First Response (TTR)

    Measured: Baseline to Date of CR or PR (Estimated up to 6 Months)

  11. Progression Free Survival (PFS)

    Measured: Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months)

  12. Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR

    Measured: Baseline through Measured Progressive Disease (Estimated up to 6 Months)

  13. Overall Survival (OS) (Dose Expansion Arms Only)

    Measured: Baseline to Date of Death from Any Cause (Estimated up to 2 Years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2016 (estimated)
  2. Study start29 Sep 2016
  3. Primary completion10 Feb 2021
  4. Study completion24 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
210 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02857270
Sponsor's protocol ID
16419
Other IDs
I8S-MC-JUAB, 2016-001907-21, 2016
Status last verified
Nov 2022
First submitted
3 Aug 2016
Last updated
22 Nov 2022
Results posted
No
Data monitoring committee
No
Individual data sharing
No

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.

    PubMed 31744895

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY3214996, Midazolam and Abemaciclib in people with Advanced Cancer and Metastatic Melanoma, run by Eli Lilly and Company at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Australia, Japan, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (21 Days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02857270, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2022.

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