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Metastatic Colon AdenocarcinomaPhase 1/2NCT04616183

LY3214996 and Cetuximab Alone or in Combination With Abemaciclib for the Treatment of Unresectable or Metastatic Colorectal Cancer

A Phase 1/2 study testing Abemaciclib, Cetuximab and ERK1/2 Inhibitor LY3214996 in people with Metastatic Colon Adenocarcinoma and Metastatic Colorectal Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase Ib/II trial investigates the side effects and best dose of LY3214996 when given together with cetuximab alone or in combination with abemaciclib and to see how well they work in treating patients with colorectal cancer that cannot be removed by surgery (unresectable) and/or has spread to other places in the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Abemaciclib, Cetuximab and ERK1/2 Inhibitor LY3214996
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
2 Dec 2020to 31 Dec 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Provision of signed Informed Consent prior to any screening procedures being performed. The informed consent process will be conducted in accordance with MD Anderson Office of Clinical Research SOP 04 and as indicated in Appendix 2.
  • Age ≥18 years at the time of informed consent.
  • Histologically (or cytologically) confirmed diagnosis of adenocarcinoma of the colon or rectum, with clinical confirmation of unresectable and/or metastatic disease that is measureable according to RECIST1.1 criteria.
  • Baseline tissue-based KRAS, NRAS, EGFR, BRAF wild-type tumor. If MEK1 was tested, must be wild-type tumor
  • Prior treatment with at least one systemic chemotherapy regimen for mCRC, or recurrence/progression with development of unresectable or metastatic disease within 6 months of adjuvant chemotherapy for resected colorectal cancer.
  • Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade .1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the participant did not receive radiotherapy).
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  • Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization
  • Left-sided primary tumor
  • Prior treatment with, and progression on, anti-EGFR therapy (cetuximab or panitumumab).
  • ECOG performance status ≤ 1.
  • Adequate bone marrow, organ function and laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,
  • Hemoglobin (Hgb) ≥ 9 g/dL with or without transfusions,
  • Platelets (PLT) ≤ 100 x 109/L without transfusions,
  • AST and/or ALT ≤ 2.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN and < 2 mg/dL Note: Participants who have a total bilirubin level > 1.5 x ULN will be allowed if their indirect bilirubin level is ≤ 1.5 x ULN
  • Serum Creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50mL/min at screening.
  • QTc interval ≤ 480 ms (preferably the mean from triplicate ECGs);
  • Able to take oral medications.
  • Female participants are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential.
  • Note: Permitted contraception methods include: male condom with spermicide, female condom with spermicide, diaphragm with spermicide, cervical sponge, or cervical cap with spermicide. Also see the definition of highly effective method of contraception in Appendix 1. These should be communicated to the participants and their understanding confirmed. For all females, the pregnancy test result must be negative within 24 hours of starting treatment on study and within 24 hours prior to each cycle. Males must agree to take appropriate precautions to avoid fathering a child from screening through 100 days following the end of therapy.

Who cannot join

  • History of a Grade 3 or 4 allergic reaction or intolerability attributed to cetuximab.
  • Right-sided or transverse colonic primary tumor.
  • Baseline tissue-based KRAS, NRAS, EGFR, BRAF and MEK1 mutated tumor
  • Active infection requiring concurrent antibiotic use.
  • Currently using concomitant medications that are strong inhibitors or inducers of CYP3A4.
  • Previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor.
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  • Any known symptomatic brain metastasis. Note: Participants previously treated or untreated for this condition who are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Known brain metastases must be stable for ≥ 4 weeks, with imaging (e.g., magnetic resonance imaging [MRI] or computed tomography [CT]) demonstrating no current evidence of progressive brain metastases at screening.
  • Known leptomeningeal disease
  • Previous or concurrent malignancy within 3 years of study entry, with the following exceptions: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy; other solid tumors treated curatively without evidence of recurrence for at least 3 years prior to study entry.
  • Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) <6 months prior to screening,
  • Symptomatic chronic heart failure (i.e. Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality <6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia;
  • The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
  • Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mm Hg, despite current therapy;
  • The participant has active systemic bacterial infection (requiring intravenous (IV) antibiotics at time of initiating study treatment,) fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C (for example, hepatitis B surface antigen positive.) Screening is not required for enrollment.; Known history of acute or chronic pancreatitis (history of acute pancreatitis with no recurrent events in the prior 24 months are permitted)
  • Impaired gastrointestinal function or disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).
  • Any other condition that would, in the Investigator's judgment, contraindicate the participants participation in the clinical study due to safety concerns or compliance with clinical study procedures.
  • For participants receiving abemaciclib: The participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • Major surgery ≤ 6 weeks prior to starting study drug or failure to recover from side effects of such procedure at the discretion of the treating investigator.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Open-Label Phase 1b/2 Study of Cetuximab Administered in Combination With LY3214996 (ERK 1/2 Inhibitor) or Cetuximab in Combination With LY3214996 and Abemaciclib in Patients With Metastatic, Anti-EGFR-Refractory Colorectal Cancer

This phase Ib/II trial investigates the side effects and best dose of LY3214996 when given together with cetuximab alone or in combination with abemaciclib and to see how well they work in treating patients with colorectal cancer that cannot be removed by surgery (unresectable) and/or has spread to other places in the body (metastatic). Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. LY3214996 and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving LY3214996 and cetuximab alone or in combination with abemaciclib may help treat patients with colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ERK1/2 inhibitor LY3214996 (LY3214996) administered in combination with cetuximab. (Phase 1b) II. Determine the MTD and RP2D of LY3214996 administered in combination with cetuximab plus abemaciclib. (Phase 1b) III. Assess the preliminary antitumor activity of the treatment combinations based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. (Phase 2)

SECONDARY OBJECTIVES:

  1. Assess the preliminary antitumor activity of the treatment combinations based on RECIST v.1.1. (Phase 1b) II. Characterize the safety profile of the treatment combinations (DLTs). III. Evaluate for pERK and Ki67 inhibition.

EXPLORATORY OBJECTIVES:

  1. Assess blood- and tissue-based predictive biomarkers of activity and immune effects upon treatment with cetuximab, LY3214996, and abemaciclib.

II. Demonstrate feasibility of establishing patient-derived xenograft (PDX) models in matched patients with cetuximab-refractory metastatic colorectal cancer (mCRC) to evaluate for biomarkers of response and mechanisms of resistance.

III. Explore mechanisms of resistance to cetuximab plus LY3214996 and cetuximab, LY3214996, plus abemaciclib.

OUTLINE: This is a phase Ib, dose-escalation study of ERK1/2 inhibitor LY3214996 followed by a phase II study. Patients are assigned to 1 of 2 arms.

ARM A: Patients receive ERK1/2 inhibitor LY3214996 orally (PO) once daily (QD) on days 1-28 and cetuximab intravenously (IV) over 1-2 hours on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive ERK1/2 inhibitor LY3214996 and cetuximab as in Arm A. Patients also receive abemaciclib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Abemaciclib, Cetuximab, ERK1/2 Inhibitor LY3214996
Medical subject headings
Colonic Neoplasms, Colorectal Neoplasms, Rectal Neoplasms

What participants receive

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

  • AbemaciclibDrug

    Also called LY-2835219, LY2835219, Verzenio

    Given PO

  • CetuximabBiological

    Also called Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody

    Given IV

  • ERK1/2 Inhibitor LY3214996Drug

    Also called LY 3214996, LY3214996

    Given PO

Study groups in NCT04616183
Study groupRoleWhat they receive
Arm A (ERK1/2 inhibitor LY3214996, cetuximab)ExperimentalPatients receive ERK1/2 inhibitor LY3214996 PO QD on days 1-28 and cetuximab IV over 1-2 hours on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Cetuximab; Drug: ERK1/2 Inhibitor LY3214996
Arm B (ERK1/2 inhibitor LY3214996, cetuximab, abemaciclib)ExperimentalPatients receive ERK1/2 inhibitor LY3214996 and cetuximab as in Arm A. Patients also receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Abemaciclib; Biological: Cetuximab; Drug: ERK1/2 Inhibitor LY3214996

What is being measured

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

  1. Best overall response (complete response [CR] + partial response [PR])

    Response rate will be calculated based on the number of patients in the evaluable population experiencing a radiographic response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (either CR or PR) relative to the total number of patients in the efficacy evaluable population. A 95% confidence interval will be estimated around this population.

    Measured: From the start of the treatment until disease progression, assessed up to 1 year

Secondary outcomes (3)

  1. Overall survival

    The Kaplan-Meier method will be used to estimate both the survival curves and the median survival time. The 95% confidence intervals for median survival times will also be calculated.

    Measured: From enrollment until death, assessed up to 1 year

  2. Progression-free survival (PFS)

    The Kaplan-Meier method will be used to estimate the proportion of subjects without progression or death overtime and the median PFS. The 95% confidence intervals for median PFS will also be displayed.

    Measured: From enrollment until death or disease progression as defined by RECIST version 1.1 criteria for the evaluable population, assessed up to 1 year

  3. Incidence of adverse events

    Will be tabulated for adverse events according to Common Terminology Criteria for Adverse Events version 5.0 across all grades.

    Measured: Up to 30 days

Timeline

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

  1. First posted4 Nov 2020
  2. Study start2 Dec 2020
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04616183
Sponsor's protocol ID
2019-1016
Other IDs
NCI-2020-06350, 2019-1016, R01CA187238
Status last verified
Sep 2026
First submitted
31 Aug 2020
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Abemaciclib, Cetuximab and ERK1/2 Inhibitor LY3214996 in people with Metastatic Colon Adenocarcinoma and Metastatic Colorectal Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

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 21 inclusion and 21 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: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

This study is still under way. Results are not available in the source record yet.

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?

Best overall response (complete response [CR] + partial response [PR]) (time frame: From the start of the treatment until disease progression, assessed up to 1 year). 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 NCT04616183.

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 5 Oct 2026.

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