A Study in Advanced Cancers Using Ramucirumab (LY3009806) and Other Targeted Agents

An Open-Label, Phase 1a/1b Study of Ramucirumab in Combination With Other Targeted Agents in Advanced Cancers

The main purpose of this study is to evaluate the safety of ramucirumab in combination with other targeted agents in participants with advanced cancers.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Mantle Cell Lymphoma; Advanced Cancer
• Intervention / Treatment: Drug: Abemaciclib; Drug: Ramucirumab; Drug: Merestinib

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69373
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Marseille, France, 13385
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Uab Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Study Arm 1:

  • histopathologically confirmed advanced or metastatic colorectal cancer, excluding primary tumors of appendiceal origin
  • have at least 1 measurable lesion assessable by radiological imaging. Tumor lesions located in a previously irradiated area are considered measureable if progression has been demonstrated in such lesions
  • have received prior second-line treatment with oxaliplatin and/or irinotecan, and no other licensed/standard-of-care therapies are available. If the participant has RAS wild type colorectal cancer, he or she also must have received prior treatment with an epidermal growth factor receptor monoclonal antibody

• Study Arm 2

  • pathologically confirmed mantle cell lymphoma (MCL), with (a) measurable nodal disease on positron emission tomography computed tomography (PET-CT) per Lugano classification. Prior to enrollment, pathology must be reviewed and confirmed at the investigational site where the participant is entered
  • have MCL that relapsed after or is refractory to (a) first-line combination chemotherapy with or without stem cell transplant and (b) at least 1 other locally available therapy
  • provide a newly obtained tumor tissue sample. Tumor tissue biopsies may be taken by surgical resection, core needle biopsy, or fine needle biopsy

• All Study Arms:

  • have not received previous systemic therapy (including investigational agents) targeting programmed cell death protein 1 (PD-1)/ PD-1 ligand (PDL 1) or PD-1/PDL-2 signaling pathways. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anticytotoxic T-lymphocyte-associated antigen-4 antibody, is not permitted
  • have adequate organ function
  • are, in the judgment of the investigator, appropriate candidates for experimental therapy after available standard therapies have failed to provide clinical benefit
  • have discontinued all previous treatments for cancer and recovered from the acute effects of therapy, other than less than or equal to Grade 2 neuropathy or nonserious and nonlife-threatening toxicities such as alopecia, altered taste, and nail changes
  • have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale
  • men and women must agree to the use an effective method of contraception during the study and for at least 3 months post last dose of study drug administration. Women of child-bearing potential must have negative serum and urine pregnancy tests at screening and during each treatment cycle, respectively

Exclusion Criteria:

• Study Arm 1

  • have a serious illness or medical condition including, but not limited to, the following: active or uncontrolled clinically serious infection; inadequate biliary drainage with evidence of unresolved biliary obstruction

• Study Arm 2

  • have a serious illness or medical condition including, but not limited to, the following: active or uncontrolled clinically serious infection, including chronic viral hepatitis

• All Arms:

  • have prior or concurrent malignancies, inclusive of hematologic, primary brain tumor, sarcoma, and other solid tumors, unless in complete remission with no therapy for a minimum of 5 years
  • have active gastrointestinal (GI) disease characterized by inflammatory bowel disease, malabsorption syndrome, or frequent Grade 2 or more diarrhea
  • are pregnant or breastfeeding
  • have previously documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression
  • have experienced any of the following: a major surgical procedure, significant traumatic injury, non-healing wound, peptic ulcer, or bone fracture less than or equal to 28 days prior to enrollment, or placement of a subcutaneous venous access device less than or equal to 7 days prior to the first dose of study treatment unless the procedure is of low risk of bleeding in the judgment of the investigator
  • have an elective or a planned major surgery during the course of the trial
  • have a known allergy or hypersensitivity reaction to any of the treatment components
  • have uncontrolled hypertension
  • have experienced any arterial thromboembolic event within 6 months prior to enrollment
  • have experienced any Grade 3 or 4 venous thromboembolic event that is considered by the investigator to be life threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within 6 months prior to enrollment
  • have a history of GI perforation and/or fistulae within 6 months prior to enrollment
  • have experienced any bleeding episode considered life-threatening, or any Grade 3 or 4 GI/variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention
  • have congestive heart failure or poorly controlled cardiac arrhythmia per New York Heart Association Class II-IV heart disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ramucirumab + Merestinib; Ramucirumab intravenously (IV) on day 1 and day 15 in combination with merestinib orally once a day over a 28 day cycle. Participants receiving benefit may continue until disease progression.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; Drug: Merestinib; Administered orally; Other Names: LY2801653
Experimental: Ramucirumab + Abemaciclib; Ramucirumab IV on day 1 and day 15 in combination with abemaciclib orally twice a day over a 28 day cycle. Participants receiving benefit may continue until disease progression. On June 21st 2017 the Ramucirumab + Abemaciclib arm was cancelled with no participants enrolled.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Ramucirumab; Administered IV; Other Names: LY3009806

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab, Merestinib and Abemaciclib	Predose Cycle 1 Day 1 through Predose Cycle 6 Day 1 (28 day cycles)
Proportion of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]	Baseline through Measured Progressive Disease or Death (Estimated up to 24 months)
Progression Free Survival (PFS)	Baseline through Measured Progressive Disease or Death (Estimated up to 24 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Saleh M, Cassier PA, Eberst L, Naik G, Morris VK, Pant S, Terret C, Gao L, Long A, Mao H, McNeely S, Wagner EK, Carlesi RM, Fu S. Phase I Study of Ramucirumab Plus Merestinib in Previously Treated Metastatic Colorectal Cancer: Safety, Preliminary Efficacy, and Pharmacokinetic Findings. Oncologist. 2020 Nov;25(11):e1628-e1639. doi: 10.1634/theoncologist.2020-0520. Epub 2020 Jul 17.

Helpful Links

• Click here for more information about this study: A Study in Advanced Cancers Using Ramucirumab (LY3009806) and Other Targeted Agents

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2016
• Primary Completion (Actual): November 5, 2018
• Study Completion (Actual): January 22, 2019

Study Registration Dates

• First Submitted: April 18, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimate): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 2, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms; Lymphoma, Mantle-Cell; Antineoplastic Agents; Ramucirumab
• Other Study ID Numbers: 16165; I4T-MC-JVDK (Other Identifier: Eli Lilly and Company); 2015-004381-28 (EudraCT Number)