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

Phase 2

Recruiting

• Conditions: Unresectable Metastatic Colorectal Cancer
• Interventions: Drug: ABBV-400; Drug: Bevacizumab; Drug: Folinic Acid; Drug: Fluorouracil; Drug: Irinotecan

• Registration Number: NCT06107413
• Lead Sponsor: AbbVie

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-25
• Study First Submitted QC: 2023-10-25
• Study First Posted: 2023-10-30
• Study Start: 2023-11-12
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-24
• Primary Completion: 2026-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 206

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ABBV-400+FFB A Low	ABBV-400	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.
ABBV-400+Fluorouracil, Folinic Acid, and Bevacizumab (FFB) A	ABBV-400	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.
ABBV-400+FFB A High	ABBV-400	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.
ABBV-400+FFB B Low	ABBV-400	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.
ABBV-400+Fluorouracil, Folinic Acid, and Bevacizumab (FFB) A	Folinic Acid	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.
ABBV-400+FFB B	ABBV-400	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.
ABBV-400+FFB B High	ABBV-400	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.
ABBV-400+Fluorouracil, Folinic Acid, and Bevacizumab (FFB) A	Bevacizumab	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.
ABBV-400+FFB B	Bevacizumab	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.
ABBV-400+Fluorouracil, Folinic Acid, and Bevacizumab (FFB) A	Fluorouracil	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.
ABBV-400+FFB B	Fluorouracil	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.
ABBV-400+FFB B	Folinic Acid	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.
ABBV-400+FFB A Low	Bevacizumab	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.
ABBV-400+FFB A Low	Fluorouracil	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.
ABBV-400+FFB A Low	Folinic Acid	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.
ABBV-400+FFB A High	Bevacizumab	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.
ABBV-400+FFB A High	Folinic Acid	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.
ABBV-400+FFB A High	Fluorouracil	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.
ABBV-400+FFB B Low	Bevacizumab	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.
ABBV-400+FFB B Low	Folinic Acid	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.
ABBV-400+FFB B Low	Fluorouracil	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.
ABBV-400+FFB B High	Bevacizumab	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.
ABBV-400+FFB B High	Folinic Acid	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.
ABBV-400+FFB B High	Fluorouracil	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.
FFB+Irinotecan (Standard of Care [SOC])	Bevacizumab	Participants will receive SOC during the 3 year study duration.
FFB+Irinotecan (Standard of Care [SOC])	Folinic Acid	Participants will receive SOC during the 3 year study duration.
FFB+Irinotecan (Standard of Care [SOC])	Fluorouracil	Participants will receive SOC during the 3 year study duration.
FFB+Irinotecan (Standard of Care [SOC])	Irinotecan	Participants will receive SOC during the 3 year study duration.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with Objective Response	Up to 24 Weeks	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.
Progression Free Survival (PFS)	Up to 11 Months	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Best Overall Response (BOR)	Up to 18 Weeks	BOR is defined as confirmed CR or confirmed PR, or stable disease (SD) based on RECIST, version 1.1 as determined by the investigator.
Duration of Response (DOR)	Up to 7 Months	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.
Overall Survival (OS)	Up to 3 Years	OS is defined as the time from first dose of study drug to the event of death from any cause.

Trial Locations

Locations (37)

Highlands Oncology Group, PA /ID# 259424; 🇺🇸 Springdale, Arkansas, United States

City of Hope National Medical Center /ID# 257576; 🇺🇸 Duarte, California, United States

Northwestern University Robert H. Lurie Comprehensive Cancer Center /ID# 260563; 🇺🇸 Chicago, Illinois, United States

Fort Wayne Medical Oncology and Hematology- South Office /ID# 259601; 🇺🇸 Fort Wayne, Indiana, United States

Community Health Network, Inc. /ID# 257078; 🇺🇸 Indianapolis, Indiana, United States

Duke Cancer Center /ID# 257236; 🇺🇸 Durham, North Carolina, United States

Medical University of South Carolina /ID# 258486; 🇺🇸 Charleston, South Carolina, United States

MD Anderson Cancer Center /ID# 258713; 🇺🇸 Houston, Texas, United States

Millennium Research and Clinical Development /ID# 257780; 🇺🇸 Houston, Texas, United States

Virginia Cancer Specialists - Fairfax /ID# 257261; 🇺🇸 Fairfax, Virginia, United States

Imelda Ziekenhuis /ID# 257082; 🇧🇪 Bonheiden, Antwerpen, Belgium

Universitair Ziekenhuis Antwerpen /ID# 257080; 🇧🇪 Edegem, Antwerpen, Belgium

Universitair Ziekenhuis Leuven /ID# 257079; 🇧🇪 Leuven, Vlaams-Brabant, Belgium

AZ-Delta /ID# 257084; 🇧🇪 Roeselare, West-Vlaanderen, Belgium

Institut Jules Bordet /ID# 257625; 🇧🇪 Anderlecht, Belgium

Tel Aviv Sourasky Medical Center /ID# 257090; 🇮🇱 Tel Aviv, Tel-Aviv, Israel

Hadassah /ID# 257088; 🇮🇱 Jerusalem, Yerushalayim, Israel

Aichi Cancer Center Hospital /ID# 257286; 🇯🇵 Nagoya-shi, Aichi, Japan

National Cancer Center Hospital East /ID# 257282; 🇯🇵 Kashiwa-shi, Chiba, Japan

Kyoto University Hospital /ID# 257287; 🇯🇵 Kyoto-shi, Kyoto, Japan

Shizuoka Cancer Center /ID# 257288; 🇯🇵 Sunto-gun, Shizuoka, Japan

National Cancer Center Hospital /ID# 257284; 🇯🇵 Chuo-ku, Tokyo, Japan

Chonnam National University Hwasun Hospital /ID# 258366; 🇰🇷 Hwasun-gun, Jeonranamdo, Korea, Republic of

Seoul National University Hospital /ID# 257493; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Asan Medical Center /ID# 257845; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Samsung Medical Center /ID# 257571; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Yonsei University Health System Severance Hospital /ID# 257492; 🇰🇷 Seoul, Korea, Republic of

Hospital Universitario Vall d'Hebron /ID# 257383; 🇪🇸 Barcelona, Spain

Hospital Universitario 12 de Octubre /ID# 257384; 🇪🇸 Madrid, Spain

Hospital Universitario HM Sanchinarro /ID# 258549; 🇪🇸 Madrid, Spain

Hospital Universitario Miguel Servet /ID# 257388; 🇪🇸 Zaragoza, Spain

Kaohsiung Chang Gung Memorial Hospital /ID# 257675; 🇨🇳 Kaohsiung City, Kaohsiung, Taiwan

National Taiwan University Hospital /ID# 257639; 🇨🇳 Taipei City, Taipei, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 257637; 🇨🇳 Kaohsiung, Taiwan

National Cheng Kung University Hospital /ID# 257638; 🇨🇳 Tainan, Taiwan

Taipei Veterans General Hosp /ID# 257636; 🇨🇳 Taipei, Taiwan

Linkou Chang Gung Memorial Hospital /ID# 257640; 🇨🇳 Taoyuan City, Taiwan