ABBV-400 + Chemotherapy for Colorectal Cancer

Recruiting at 64 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Must be taking: Fluorouracil, Folinic acid, Bevacizumab

Must not be taking: Anticancer therapy

Disqualifiers: BRAF V600E mutation, dMMR+/MSI-H, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

280 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ABBV-400, combined with three existing drugs to treat advanced colorectal cancer in adults. It aims to find the best dose that controls cancer growth and minimizes side effects. The study involves regular hospital visits and various medical tests.

Will I have to stop taking my current medications?

The trial requires that you have not received any anticancer therapy, including chemotherapy, radiation, immunotherapy, biologic, or investigational therapy, within 28 days or 5 half-lives of the drug (whichever is shorter) before starting ABBV-400. This means you may need to stop certain medications before joining the trial.

What safety data exists for ABBV-400 and related treatments in colorectal cancer?

Bevacizumab, used in combination with chemotherapy for colorectal cancer, has been associated with side effects like gastrointestinal perforation (a hole in the stomach or intestines), bleeding, blood clots, and protein in the urine. However, in some studies, it was generally well-tolerated with no specific adverse reactions directly linked to bevacizumab. Irinotecan and 5-fluorouracil, often used together, have shown safety in treating colorectal cancer, with manageable side effects. ^{1 2 3 4 5}

What makes the drug ABBV-400 + Chemotherapy unique for colorectal cancer?

The drug ABBV-400 combined with chemotherapy is unique because it includes Telisotuzumab adizutecan (ABBV-400), which is not a standard component in existing colorectal cancer treatments. This combination may offer a novel approach by potentially targeting cancer cells differently compared to traditional regimens like FOLFOX or FOLFIRI, which are commonly used with bevacizumab. ^{4 6 7 8 9}

What data supports the effectiveness of the drug ABBV-400 + Chemotherapy for Colorectal Cancer?

Research shows that bevacizumab, when combined with chemotherapy drugs like irinotecan, fluorouracil, and leucovorin, provides a survival benefit in metastatic colorectal cancer. This suggests that similar combinations, like those in the ABBV-400 trial, may also be effective. ^{1 4 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with confirmed unresectable metastatic colorectal cancer that can be measured by certain medical criteria. Participants must have been treated before and are able to attend regular study visits at a participating institution.

Inclusion Criteria

My colorectal cancer cannot be removed by surgery and has spread.

You have a quantifiable illness according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Participants receive escalating doses of ABBV-400 in combination with FFB on two different schedules

Approximately 3 years

Regular visits at approved institutions

Dose Optimization

Participants receive low or high doses of ABBV-400 in combination with FFB or SOC based on safety lead-in results

Approximately 3 years

Regular visits at approved institutions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-400
• Bevacizumab
• Fluorouracil
• Folinic Acid
• Irinotecan

Trial Overview The trial is testing ABBV-400, an experimental drug, in combination with Fluorouracil, Folinic Acid, and Bevacizumab for treating colorectal cancer. It involves different doses of ABBV-400 and compares it to the standard chemotherapy regimen in about 206 patients worldwide over approximately 3 years.

How Is the Trial Designed?

Group I: Stage 3: ABBV-400+FFB B Low Experimental Treatment 4 Interventions

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/expansion, during the 3 year study duration.

Group II: Stage 3: ABBV-400+Bevacizumab C High Experimental Treatment 2 Interventions

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.

Group III: Stage 2: FFB+Irinotecan (Standard of Care [SOC]) Experimental Treatment 4 Interventions

Participants will receive SOC during the 3 year study duration.

Group IV: Stage 2: ABBV-400+FFB A Low Experimental Treatment 4 Interventions

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.

Group V: Stage 2: ABBV-400+FFB A High Experimental Treatment 4 Interventions

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.

Group VI: Stage 1: ABBV-400+FFB B Experimental Treatment 4 Interventions

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.

Group VII: Stage 1: ABBV-400+FFB A Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a phase III study, both bevacizumab (BV) combined with irinotecan, fluorouracil, and leucovorin (IFL) and oxaliplatin with fluorouracil and leucovorin (FOLFOX) showed significant improvements in progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer, regardless of whether they responded to the initial treatment.

The study found that even nonresponders to initial therapy benefited from these superior treatments, indicating that tumor response is not necessary for patients to experience survival benefits from these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. Grothey, A., Hedrick, EE., Mass, RD., et al.[2022]

In a study of 213 patients with metastatic colorectal cancer, the addition of bevacizumab (BV) to the FOLFOX4 regimen significantly improved median progression-free survival (PFS) from 9.9 months to 17.0 months and overall survival (OS) from 20.5 months to 38.8 months.

The results suggest that adding BV to FOLFOX4 provides substantial survival benefits, and maintenance therapy with 5-fluorouracil plus leucovorin during oxaliplatin suspension may further enhance survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis on the efficacy of bevacizumab with FOLFOX as a first-line treatment in Japanese patients with metastatic colorectal cancer. Suenaga, M., Mizunuma, N., Matsusaka, S., et al.[2015]

The modified FOLFIRI regimen, which includes irinotecan, 5-fluorouracil, and a low dose of leucovorin, demonstrated a 47.8% overall response rate in 44 patients with recurrent or metastatic colorectal cancer, indicating its efficacy as a first-line treatment.

The treatment was well-tolerated, with mild and manageable toxicities; only a few patients experienced severe side effects, such as Grade 3/4 leukopenia and diarrhea, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, continuous 5-fluorouracil, and low dose of leucovorin (modified FOLFIRI) as first line of therapy in recurrent or metastatic colorectal cancer. Lee, MA., Byun, JH., Shim, BY., et al.[2019]

In a study of 34 patients with metastatic colorectal cancer who did not respond to first-line oxaliplatin-based chemotherapy, the combination of FOLFIRI and bevacizumab (BV) showed an overall response rate of 23.5% and a median overall survival of 651 days, indicating its efficacy as a second-line treatment.

Baseline levels of carbohydrate antigen 125 (CA125) were identified as an independent negative predictor of progression-free survival and overall survival, suggesting it could serve as a useful biomarker for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of the efficacy of FOLFIRI plus bevacizumab as second-line treatment in metastatic colorectal cancer patients. Suenaga, M., Matsusaka, S., Ueno, M., et al.[2021]

In a study of 63 patients with KRAS wild-type metastatic colorectal cancer, the combination of irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment was found to be safe and well tolerated, with a toxicity profile consistent with the individual drugs.

The treatment resulted in a median progression-free survival of 6.1 months and a median overall survival of 11.9 months, indicating a significant level of disease control in patients who had already undergone multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer. Larsen, FO., Markussen, A., Nielsen, D., et al.[2018]

In a study involving 27 heavily pretreated patients with metastatic colorectal cancer, the combination of irinotecan, cetuximab, and bevacizumab was well tolerated and resulted in a progression-free survival (PFS) of 8.3 months and a median overall survival (mOS) of 12.0 months.

The addition of bevacizumab to the treatment regimen showed a trend towards improved outcomes in patients without KRAS mutations, suggesting that this combination therapy may be particularly effective for certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer. Larsen, FO., Pfeiffer, P., Nielsen, D., et al.[2018]

In a phase Ib study involving 28 patients with metastatic colorectal cancer, the combination of trifluridine/tipiracil, irinotecan, and bevacizumab showed moderate antitumor activity, with 19% of patients achieving a partial response and 5 having stable disease for over 4 months.

However, the treatment was associated with a high risk of severe myelotoxicity, as 86% of patients experienced grade ≥3 neutropenia, leading to significant dose reductions and delays in 94% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, Irinotecan, and Biweekly Trifluridine/Tipiracil for Metastatic Colorectal Cancer: MODURATE, a Phase Ib Study. Taniguchi, H., Yamazaki, K., Masuishi, T., et al.[2023]

In a study of six patients with unresectable colorectal cancer treated with bevacizumab, the combination chemotherapy was well-tolerated, with most adverse drug reactions being grade 2 or less.

Only one patient experienced grade 3 neutropenia, and there were no specific adverse effects directly related to bevacizumab, suggesting it can be safely used in combination with chemotherapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical experience in treatment with bevacizumab for unresectable colorectal cancer]. Fujimoto, T., Yoshimatsu, K., Yokomizo, H., et al.[2016]

In a study of patients with advanced colorectal cancer, those who received bolus chemotherapy with 5-fluorouracil and leucovorin had a median survival of 11 months, compared to 8 months for those who did not receive chemotherapy, indicating a significant survival benefit of 3 months (p = 0.009).

The analysis confirmed that both chemotherapy and the location of metastases were significant factors influencing survival, suggesting that chemotherapy can be an effective treatment option for patients with irresectable metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of 5-FU-based bolus chemotherapy on survival in patients with advanced colorectal cancer. Van Halteren, HK., Roumen, RM., Coebergh, JW., et al.[2013]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Retrospective analysis on the efficacy of bevacizumab with FOLFOX as a first-line treatment in Japanese patients with metastatic colorectal cancer. [2015]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Irinotecan, continuous 5-fluorouracil, and low dose of leucovorin (modified FOLFIRI) as first line of therapy in recurrent or metastatic colorectal cancer. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

Predictors of the efficacy of FOLFIRI plus bevacizumab as second-line treatment in metastatic colorectal cancer patients. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Bevacizumab, Irinotecan, and Biweekly Trifluridine/Tipiracil for Metastatic Colorectal Cancer: MODURATE, a Phase Ib Study. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

[A clinical experience in treatment with bevacizumab for unresectable colorectal cancer]. [2016]

9. Greece pubmed.ncbi.nlm.nih.gov

The impact of 5-FU-based bolus chemotherapy on survival in patients with advanced colorectal cancer. [2013]