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 and to Evaluate Safety and Efficacy of ABBV-400 in Combination With 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 (FFB) is an approved drug 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 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, ending with low or high doses of ABBV-400 in combination with FFB for continued dose optimization and expansion. Approximately 280 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 IV FFB at low or high doses determined in the safety lead in. The dose optimization arm will also include a comparator cohort in which participants will receive SOC. During the dose optimization and expansion stage, participants will receive IV ABBV-400 in combination with IV FFB at low or high doses that have been determined from the previous stages. 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: Active, not 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): 280
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet /ID# 257625
  • Antwerpen
    • Bonheiden, Antwerpen, Belgium, 2820
      • Imelda Ziekenhuis /ID# 257082
    • Edegem, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen /ID# 257080
  • Brussels Capital
    • Brussels, Brussels Capital, Belgium, 1200
      • Cliniques Universitaires UCL Saint-Luc /ID# 257081
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 257083
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven /ID# 257079
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • AZ-Delta /ID# 257084
• Germany
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin Campus Virchow-Klinikum /ID# 257785
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf /ID# 257782
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitatsklinikum Mannheim /ID# 257781
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen /ID# 258780
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitaetsklinikum Ulm /ID# 257783
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden /ID# 257787
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 257344
  • Tel Aviv, Israel, 6789140
    • Assuta Medical Center /ID# 267581
  • Central District
    • Kfar Saba, Central District, Israel, 4428164
      • Meir Medical Center /ID# 257089
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91031
      • Shaare Zedek Medical Center /ID# 259253
    • Jerusalem, Jerusalem, Israel, 91120
      • Hadassah /ID# 257088
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 257312
    • Tel Aviv, Tel Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 257090
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center Hospital /ID# 257286
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 257282
  • Kyoto
    • Kyoto, Kyoto, Japan, 606-8507
      • Kyoto University Hospital /ID# 257287
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center /ID# 257288
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 257284
• South Korea
  • Seoul, South Korea, 03722
    • Yonsei University Health System Severance Hospital /ID# 257492
  • Jeonranamdo
    • Hwasun-gun, Jeonranamdo, South Korea, 58128
      • Chonnam National University Hwasun Hospital /ID# 258366
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Seoul National University Hospital /ID# 257493
    • Seoul, Seoul Teugbyeolsi, South Korea, 05505
      • Asan Medical Center /ID# 257845
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center /ID# 257571
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall de Hebron /ID# 257383
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon /ID# 257387
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 257384
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro /ID# 258549
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia /ID# 257385
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet /ID# 257388
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 257637
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital /ID# 257638
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 257636
  • Taoyuan, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital /ID# 257640
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 833
      • Kaohsiung Chang Gung Memorial Hospital /ID# 257675
  • Taipei
    • Taipei City, Taipei, Taiwan, 100
      • National Taiwan University Hospital /ID# 257639
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona /ID# 262610
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group, PA /ID# 259424
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center /ID# 257576
    • Irvine, California, United States, 92618
      • City of Hope - Orange County Lennar Foundation Cancer Center /ID# 268365
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine /ID# 257494
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital Jacksonville /ID# 262609
  • Illinois
    • Chicago, Illinois, United States, 60607
      • University of Illinois Hospital and Health Sciences System /ID# 257300
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine - Northwestern Memorial Hospital /ID# 260563
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology- South Office /ID# 259601
    • Indianapolis, Indiana, United States, 46202-5116
      • Indiana University Melvin and Bren Simon Cancer Center /ID# 258789
    • Indianapolis, Indiana, United States, 46250-2042
      • Community Health Network, Inc. /ID# 257078
  • Louisiana
    • Henderson, Louisiana, United States, 89052
      • Comprehensive Cancer Centers of Nevada /ID# 257642
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - Rochester /ID# 257301
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health Levine Cancer Institute /ID# 258840
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute /ID# 257236
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University, Knight Cancer Institute- /ID# 259190
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina /ID# 258486
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute /ID# 257949
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center /ID# 258713
    • Houston, Texas, United States, 77090-3063
      • Texas Oncology PA /ID# 257780
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute - Fairfax - Innovation Park Drive /ID# 257448
    • Fairfax, Virginia, United States, 22031
      • 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.
• Progressed on only one first-line (1L) systemic treatment of combination chemotherapy in the metastatic setting with or without targeted therapy.

Exclusion Criteria:

• Harbor the BRAF V600E mutation.
• dMMR+/MSI-H.
• 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: Stage 1: ABBV-400+FFB A; Participants will receive escalating ABBV-400 in combination with Fluorouracil, Folinic Acid, and Bevacizumab (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: Stage 1: 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: Stage 2: 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: Stage 2: 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: Stage 2: 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
Experimental: Stage 3: ABBV-400+Bevacizumab C High; Participants will receive ABBV-400 in combination with Bevacizumab at the high dose determined in the safety lead in on dose schedule C as part of the dose optimization/expansion, during the 3 year study duration.	Drug: ABBV-400; Intravenous (IV) Infusion; Drug: Bevacizumab; IV Infusion
Experimental: Stage 3: 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 A as part of the dose optimization/expansion, 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Percentage of Participants with Objective Response	OR is defined as complete response (CR) or 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
Number of Participants with Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.	Up to 3 Years

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): December 1, 2026
• Study Completion (Estimated): December 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): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Cancer; Bevacizumab; Fluorouracil; Folinic Acid; ABBV-400; Unresectable Metastatic Colorectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Bevacizumab; Irinotecan; Fluorouracil; Leucovorin
• Other Study ID Numbers: M24-311; 2023-505110-14 (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 clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about 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

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