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Advanced Solid TumorPhase 1/2NCT04165031

A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation

A Phase 1/2 study testing LY3499446, Abemaciclib and Cetuximab in people with Advanced Solid Tumor and Non-Small Cell Lung Cancer, run by Eli Lilly and Company at 6 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LY3499446, Abemaciclib and Cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
6 sitesin 2 countries
Study dates
28 Nov 2019to 30 Oct 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body
  • For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health
  • Participants must be willing to use highly effective birth control
  • Participants must have adequate organ function
  • Participants must be able to swallow capsules

Who cannot join

  • Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled
  • Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months
  • Participants must not have cancer of the central nervous system that is not stable
  • Participants must not be pregnant or breastfeeding
  • Participants must not use herbal supplements

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • Memorial Sloan Kettering Cancer Center

    Harrison, New York, 10604

  • Indiana Univ Melvin & Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Memorial Sloan Kettering Cancer Center

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10022

Other trials in United States

Australia2 sites

  • St Vincent's Hospital

    Darlinghurst, New South Wales, 2010

  • Linear Clinical Research Ltd

    Nedlands, Western Australia, 6009

Other trials in Australia

About this study

Official title: A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation

The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation.

Being tested
LY3499446, Abemaciclib, Cetuximab, Erlotinib, Docetaxel
Medical subject headings
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 NCT04165031
Study groupRoleWhat they receive
LY3499446 Phase 1 Cohort A1 High DoseExperimentalParticipants received high dose LY3499446 as oral monotherapy twice daily (BID) in 21-day cycles.
Receives: Drug: LY3499446
LY3499446 Phase 1 Cohort AO Mid DoseExperimentalParticipant received mid dose LY3499446 as oral monotherapy once every other day (QOD) in 21-day cycles.
Receives: Drug: LY3499446
LY3499446 Phase 1 Cohort A-2 Low DoseExperimentalParticipants received low dose LY3499446 as oral monotherapy once daily (QD) in 21-Day cycles.
Receives: Drug: LY3499446
LY3499446 + Combination Drugs Phase 1ExperimentalLY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV). This trial was terminated prior to initiation of combination therapy cohorts.
Receives: Drug: LY3499446; Drug: Abemaciclib; Drug: Cetuximab; Drug: Erlotinib
LY3499446 Monotherapy + Combination Drugs Phase 2ExperimentalLY3499446 as oral monotherapy and LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV). The trial was terminated prior to initiation of Phase 2 of this study.
Receives: Drug: LY3499446; Drug: Abemaciclib; Drug: Cetuximab; Drug: Erlotinib
Docetaxel Phase 2Active comparatorDocetaxel IV infusion. The trial was terminated prior to initiation of Phase 2 of this study.
Receives: Drug: Docetaxel

What is being measured

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

  1. Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)

    DLT is defined as an event that is clinically significant and not clearly related to disease progression or intercurrent illness that occurred within the DLT observation period of the Cycle 1 timeframe.

    Measured: Cycle 1 (21 Day Cycle)

  2. Phase 2: Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) in Colorectal Cancer (CRC) Cohorts and Other Tumors Cohort

    ORR is defined as percentage of participants who achieved a CR or PR out of all the participants treated. Tumor responses were measured and record using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) v1.1 guidelines. CR is defined as the disappearance of all targeted and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions.

    Measured: Baseline through Measured Progressive Disease

  3. Phase 2: Progression-Free Survival (PFS) Non-Small Lung Cancer (NSCLC Cohorts)

    PFS was defined as the time from study enrollment (for non-randomized cohorts)/ the time from randomization (for randomized cohorts) to the first observation of progressive disease (PD) or death without documented disease progression per RECIST V1.1 criteria.

    Measured: Baseline to Objective Progression or Death Due to Any Cause

Secondary outcomes (8)

  1. Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446

    Average concentration after the first dose of LY3499446.

    Measured: Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose

  2. Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Abemaciclib

    PK: Average Concentration at Steady State of LY3499446 in Combination with Abemaciclib

    Measured: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)

  3. Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Cetuximab

    PK: Average Concentration at Steady State of LY3499446 in Combination with Cetuximab

    Measured: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)

  4. Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Erlotinib

    PK: Average Concentration at Steady State of LY3499446 in Combination with Erlotinib

    Measured: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)

  5. Phase 1: ORR: Percentage of Participants Who Achieve CR or PR

    ORR is defined as percentage of participants who achieved a CR or PR out of all the participants treated. Tumor responses were measured and record using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) v1.1 guidelines. CR is defined as the disappearance of all targeted and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions.

    Measured: Baseline through Measured Progressive Disease (Up to 11 Months)

  6. Phase 1: PFS

    PFS was defined as the time from study enrollment (for non-randomized cohorts)/ the time from randomization (for randomized cohorts) to the first observation of progressive disease (PD) overall response or death without documented disease progression per RECIST V1.1 criteria.

    Measured: Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months)

  7. Phase 1: Duration of Response (DoR)

    DoR was defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST v1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence.

    Measured: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)

  8. Phase 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD

    DCR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed CR, confirmed PR, or SD out of all participants treatment. Best response is determined from a sequence of responses assessed. Two determinations of PR or better before progression, but not qualifying for a CR, are required for a best response of PR. CR is defined as the disappearance of all targeted and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions.

    Measured: Baseline through Measured Progressive Disease (Up to 11 Months)

Timeline

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

  1. First posted15 Nov 2019
  2. Study start28 Nov 2019
  3. Primary completion30 Oct 2020
  4. Study completion30 Oct 2020

Why it stopped: The study was terminated due to an unexpected toxicity finding.

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04165031
Sponsor's protocol ID
17501
Other IDs
J2K-MC-JZKA, 2019-003070-53, 2019
Status last verified
Oct 2021
First submitted
14 Nov 2019
Last updated
24 Nov 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LY3499446, Abemaciclib and Cetuximab in people with Advanced Solid Tumor and Non-Small Cell Lung Cancer, run by Eli Lilly and Company at 6 sites in 2 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 5 inclusion and 5 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: stopped early, as of the sponsor's last update on 24 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Australia. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (21 Day Cycle)). The study lists 3 primary outcomes in all. 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 NCT04165031.

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 24 Nov 2021.

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