Study to Assess Adverse Events and Change in Disease Activity in Previously Treated Adult Participants Receiving Intravenous (IV) ABBV-400 With Unresectable Metastatic Colorectal Cancer in Combination With IV Fluorouracil, Folinic Acid, and Bevacizumab

A Phase 2, Randomized Study to Evaluate Safety, Efficacy, and Optimal Dose of ABBV-400 in Combination With Fluorouracil, Folinic Acid, and Bevacizumab in Previously Treated Subjects With Unresectable Metastatic Colorectal Cancer

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given in combination with Fluorouracil, Folinic Acid, and Bevacizumab to adult participants to treat unresctable metastatic colorectal cancer.

ABBV-400 is an investigational drug being developed for the treatment of unresectable metastatic colorectal cancer. Fluorouracil, folinic acid, and bevacizumab is an drug approved for the treatment of unresectable metastatic colorectal cancer. Study doctors put the participants in groups called treatment arms. Each treatment arm receives a different dose of ABBV-400 in combination with fluorouracil, folinic acid, and bevacizumab (FFB) in escalating doses on two different schedules (safety lead in), followed by low or high doses of ABBV-400 in combination with FFB or fluorouracil, folinic acid, irinotecan, and bevacizumab (standard of care [SOC]) [dose optimization] on its own. Approximately 206 adult participants with unresectable metastatic colorectal cancer will be enrolled in the study in 65 sites worldwide.

In the safety lead in, participants will receive escalating intravenous (IV) ABBV-400 in combination with IV FFB on two different schedules. During the dose optimization participants will receive IV ABBV-400 in combination with FFB at low or high doses determined in the safety lead in on two different dosing schedules. The dose optimization arm will also include a comparator cohort in which participants will receive SOC. The study will run for a duration of approximately 3 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Study Overview

• Status: Recruiting
• Conditions: Unresectable Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: ABBV-400; Drug: Bevacizumab; Drug: Folinic Acid; Drug: Fluorouracil; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Estimated): 206
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Israel
  • Tel-Aviv
    • Tel Aviv, Tel-Aviv, Israel, 6423906
      • Recruiting
      • Tel Aviv Sourasky Medical Center /ID# 257090
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91120
      • Recruiting
      • Hadassah /ID# 257088
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center Hospital /ID# 257286
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East /ID# 257282
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 606-8507
      • Recruiting
      • Kyoto University Hospital /ID# 257287
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital /ID# 257284
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital /ID# 257493
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Recruiting
      • Yonsei University Health System Severance Hospital /ID# 257492
• Taiwan
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hosp /ID# 257636
  • Taipei City, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital /ID# 257639
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Recruiting
      • Highlands Oncology Group, PA /ID# 259424
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center /ID# 257576
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Recruiting
      • Northwestern University Robert H. Lurie Comprehensive Cancer Center /ID# 260563
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Recruiting
      • Fort Wayne Medical Oncology and Hematology- South Office /ID# 259601
    • Indianapolis, Indiana, United States, 46250-2042
      • Recruiting
      • Community Health Network, Inc. /ID# 257078
      • Contact: Site Coordinator; Phone Number: 317-621-4300
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Recruiting
      • Duke Cancer Center /ID# 257236
      • Contact: Site Coordinator; Phone Number: 919-668-1861
  • South Carolina
    • Charleston, South Carolina, United States, 29425-8900
      • Recruiting
      • Medical University of South Carolina /ID# 258486
  • Texas
    • Houston, Texas, United States, 77090-3063
      • Recruiting
      • Millennium Research and Clinical Development /ID# 257780
      • Contact: Site Coordinator; Phone Number: 281-440-5006
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists - Fairfax /ID# 257261

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of histologically or cytologically confirmed unresectable metastatic colorectal cancer (mCRC).
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Exclusion Criteria:

• Harbor the BRAF V600E mutation.
• dMMR+/MSI-H.
• Progressed on only one first-line (1L) systemic treatment of combination chemotherapy in the metastatic setting with or without targeted therapy.
• Received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-400.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABBV-400+Fluorouracil, Folinic Acid, and Bevacizumab (FFB) A; Participants will receive escalating ABBV-400 in combination with FFB on dose schedule A as part of the safety lead in, during the 3 year study duration.	Drug: ABBV-400; Intravenous (IV) Infusion; Drug: Bevacizumab; IV Infusion; Drug: Folinic Acid; IV Infusion; Drug: Fluorouracil; IV Infusion
Experimental: ABBV-400+FFB B; Participants will receive escalating ABBV-400 in combination with FFB on dose schedule B as part of the safety lead in, during the 3 year study duration.	Drug: ABBV-400; Intravenous (IV) Infusion; Drug: Bevacizumab; IV Infusion; Drug: Folinic Acid; IV Infusion; Drug: Fluorouracil; IV Infusion
Experimental: ABBV-400+FFB A Low; Participants will receive ABBV-400 in combination with FFB at the low dose determined in the safety lead in on dose schedule A as part of the dose optimization, during the 3 year study duration.	Drug: ABBV-400; Intravenous (IV) Infusion; Drug: Bevacizumab; IV Infusion; Drug: Folinic Acid; IV Infusion; Drug: Fluorouracil; IV Infusion
Experimental: ABBV-400+FFB A High; Participants will receive ABBV-400 in combination with FFB at the high dose determined in the safety lead in on dose schedule A as part of the dose optimization, during the 3 year study duration.	Drug: ABBV-400; Intravenous (IV) Infusion; Drug: Bevacizumab; IV Infusion; Drug: Folinic Acid; IV Infusion; Drug: Fluorouracil; IV Infusion
Experimental: ABBV-400+FFB B Low; Participants will receive ABBV-400 in combination with FFB at the low dose determined in the safety lead in on dose schedule B as part of the dose optimization , during the 3 year study duration.	Drug: ABBV-400; Intravenous (IV) Infusion; Drug: Bevacizumab; IV Infusion; Drug: Folinic Acid; IV Infusion; Drug: Fluorouracil; IV Infusion
Experimental: ABBV-400+FFB B High; Participants will receive ABBV-400 in combination with FFB at the high dose determined in the safety lead in on dose schedule B as part of the dose optimization, during the 3 year study duration.	Drug: ABBV-400; Intravenous (IV) Infusion; Drug: Bevacizumab; IV Infusion; Drug: Folinic Acid; IV Infusion; Drug: Fluorouracil; IV Infusion
Experimental: FFB+Irinotecan (Standard of Care [SOC]); Participants will receive SOC during the 3 year study duration.	Drug: Bevacizumab; IV Infusion; Drug: Folinic Acid; IV Infusion; Drug: Fluorouracil; IV Infusion; Drug: Irinotecan; IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Objective Response	OR is defined as complete response (CR) and partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as assessed by the investigator.	Up to 24 Weeks
Progression Free Survival (PFS)	PFS is defined as the time from the first dose of study drug to the first occurrence of radiographic progression based on RECIST version 1.1 as determined by the investigator or death from any cause, whichever occurs earlier.	Up to 11 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR is defined as The time from the first documented CR or PR to the first occurrence of radiographic progression per RECIST v1.1 as determined by the investigator or death from any cause, whichever occurs first.	Up to 7 Months
Overall Survival (OS)	OS is defined as the time from first dose of study drug to the event of death from any cause.	Up to 3 Years
Percentage of Participants Achieving Best Overall Response (BOR)	BOR is defined as confirmed CR or confirmed PR, or stable disease (SD) based on RECIST, version 1.1 as determined by the investigator.	Up to 18 Weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: October 25, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Bevacizumab; Fluorouracil; Folinic Acid; ABBV-400; Unresectable Metastatic Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Hematinics; Fluorouracil; Bevacizumab; Leucovorin; Irinotecan; Levoleucovorin; Folic Acid
• Other Study ID Numbers: M24-311; 2023-505110-14-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes