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

AbbVie

Status and phase: Active, not recruiting; Phase 2

Conditions: Unresectable Metastatic Colorectal Cancer

Treatments: Drug: Fluorouracil; Drug: Irinotecan; Drug: ABBV-400; Drug: Bevacizumab; Drug: Folinic Acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT06107413

2023-505110-14 (Other Identifier)

M24-311

Details and patient eligibility

About

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.

Enrollment: 280 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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280 participants in 7 patient groups

Stage 1: ABBV-400+FFB A

Experimental group

Description:

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.

Treatment:

Drug: Folinic Acid

Drug: Bevacizumab

Drug: ABBV-400

Drug: Fluorouracil

Stage 1: ABBV-400+FFB B

Experimental group

Description:

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.

Treatment:

Drug: Folinic Acid

Drug: Bevacizumab

Drug: ABBV-400

Drug: Fluorouracil

Stage 2: ABBV-400+FFB A Low

Experimental group

Description:

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.

Treatment:

Drug: Folinic Acid

Drug: Bevacizumab

Drug: ABBV-400

Drug: Fluorouracil

Stage 2: ABBV-400+FFB A High

Experimental group

Description:

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.

Treatment:

Drug: Folinic Acid

Drug: Bevacizumab

Drug: ABBV-400

Drug: Fluorouracil

Stage 2: FFB+Irinotecan (Standard of Care [SOC])

Experimental group

Description:

Participants will receive SOC during the 3 year study duration.

Treatment:

Drug: Folinic Acid

Drug: Bevacizumab

Drug: Irinotecan

Drug: Fluorouracil

Stage 3: ABBV-400+FFB B Low

Experimental group

Description:

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.

Treatment:

Drug: Folinic Acid

Drug: Bevacizumab

Drug: ABBV-400

Drug: Fluorouracil

Stage 3: ABBV-400+Bevacizumab C High

Experimental group

Description:

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.

Treatment:

Drug: Bevacizumab

Drug: ABBV-400