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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Unresectable Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: ABBV-400
* Drug: Bevacizumab
* Drug: Folinic Acid
* Drug: Fluorouracil
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-400+Fluorouracil, Folinic Acid, and Bevacizumab (FFB) A<br>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<br>* Intravenous (IV) Infusion<br>Drug: Bevacizumab<br>* IV Infusion<br>Drug: Folinic Acid<br>* IV Infusion<br>Drug: Fluorouracil<br>* IV Infusion<br>|
| Experimental: ABBV-400+FFB B<br>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<br>* Intravenous (IV) Infusion<br>Drug: Bevacizumab<br>* IV Infusion<br>Drug: Folinic Acid<br>* IV Infusion<br>Drug: Fluorouracil<br>* IV Infusion<br>|
| Experimental: ABBV-400+FFB A Low<br>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<br>* Intravenous (IV) Infusion<br>Drug: Bevacizumab<br>* IV Infusion<br>Drug: Folinic Acid<br>* IV Infusion<br>Drug: Fluorouracil<br>* IV Infusion<br>|
| Experimental: ABBV-400+FFB A High<br>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<br>* Intravenous (IV) Infusion<br>Drug: Bevacizumab<br>* IV Infusion<br>Drug: Folinic Acid<br>* IV Infusion<br>Drug: Fluorouracil<br>* IV Infusion<br>|
| Experimental: ABBV-400+FFB B Low<br>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<br>* Intravenous (IV) Infusion<br>Drug: Bevacizumab<br>* IV Infusion<br>Drug: Folinic Acid<br>* IV Infusion<br>Drug: Fluorouracil<br>* IV Infusion<br>|
| Experimental: ABBV-400+FFB B High<br>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<br>* Intravenous (IV) Infusion<br>Drug: Bevacizumab<br>* IV Infusion<br>Drug: Folinic Acid<br>* IV Infusion<br>Drug: Fluorouracil<br>* IV Infusion<br>|
| Experimental: FFB+Irinotecan (Standard of Care [SOC])<br>Participants will receive SOC during the 3 year study duration. | Drug: Bevacizumab<br>* IV Infusion<br>Drug: Folinic Acid<br>* IV Infusion<br>Drug: Fluorouracil<br>* IV Infusion<br>Drug: Irinotecan<br>* IV Infusion<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Unresectable Metastatic Colorectal Cancer, ABBV-400, Fluorouracil, Folinic Acid, Bevacizumab