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

NCT04616183 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: 2019-1016NCI-2020-06350R01CA187238
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Metastatic Colon Adenocarcinoma; Metastatic Colorectal Carcinoma; Metastatic Rectal Adenocarcinoma; Recurrent Colorectal Carcinoma; Stage III Colon Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Stage IIIA Colon Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Colon Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8; Stage IIIC Colon Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8; Stage IV Colon Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Rectal Cancer AJCC v8; Stage IVA Colon Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Rectal Cancer AJCC v8; Stage IVB Colon Cancer AJCC v8; Stage IVB Rectal Cancer AJCC v8; Stage IVC Colon Cancer AJCC v8; Stage IVC Rectal Cancer AJCC v8; Unresectable Colon Adenocarcinoma; Unresectable Colorectal Carcinoma; Unresectable Rectal Adenocarcinoma; Stage IIIA Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

• Overall survival

  From enrollment until death, assessed up to 1 year

• Progression-free survival (PFS)

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

• Incidence of adverse events

  Up to 30 days

Study Arms (2)

Arm A (ERK1/2 inhibitor LY3214996, cetuximab)

EXPERIMENTAL

Patients 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.

Biological: Cetuximab; Drug: ERK1/2 Inhibitor LY3214996

Arm B (ERK1/2 inhibitor LY3214996, cetuximab, abemaciclib)

EXPERIMENTAL

Patients 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.

Drug: Abemaciclib; Biological: Cetuximab; Drug: ERK1/2 Inhibitor LY3214996

Interventions

Abemaciclib DRUG

Given PO

Also known as: LY-2835219, LY2835219, Verzenio

Arm B (ERK1/2 inhibitor LY3214996, cetuximab, abemaciclib)

Cetuximab BIOLOGICAL

Given IV

Also known as: Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225

Arm A (ERK1/2 inhibitor LY3214996, cetuximab); Arm B (ERK1/2 inhibitor LY3214996, cetuximab, abemaciclib)

ERK1/2 Inhibitor LY3214996 DRUG

Given PO

Also known as: LY 3214996, LY3214996

Arm A (ERK1/2 inhibitor LY3214996, cetuximab); Arm B (ERK1/2 inhibitor LY3214996, cetuximab, abemaciclib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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)

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms; Rectal Neoplasms

Interventions

abemaciclib; Cetuximab; LY3214996

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christine M Parseghian, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: November 4, 2020
• Study Start: December 2, 2020
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

US (1)