ABBV-400 vs Standard Treatment for Colorectal Cancer

(AndroMETa-CRC- Trial)

Recruiting at 51 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: C-MET antibodies, ADCs

Disqualifiers: Allergy to bevacizumab, Active infection, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

460 Participants Needed

Trial Summary

What is the purpose of this trial?

Colorectal cancer (CRC) is the third most common type of cancer diagnosed worldwide and in China. The purpose of this study is to assess adverse events disease activity when comparing intravenously (IV) infused ABBV-400 to trifluridine and tipiracil (LONSURF) oral tablets plus IV infused bevacizumab in adult participants with c-Met over-expressed refractory metastatic colorectal cancer (mCRC). ABBV-400 is an investigational drug being developed for the treatment of CRC. Participants are put into treatment arms as part of 2 stages. Each treatment arm in stage 1 receives a different dose of ABBV-400. Each treatment arm in stage 2 receives the optimal dose of ABBV-400 or LONSURF plus bevacizumab. Up to approximately 460 adult participants with c-Met over-expressed (OE) refractory mCRC, will be enrolled in the study in approximately 160 sites in 15-20 countries. In stage 1, participants will receive intravenously (IV) infused ABBV-400 dose A or B. In stage 2, participants will receive the optimal dose of IV infused ABBV-400 or the standard of care (SOC), LONSURF oral tablets plus IV infused bevacizumab. The total study duration will be approximately 4 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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug ABBV-400 for colorectal cancer?

Research shows that bevacizumab, a component of the treatment, can prolong survival in colorectal cancer patients when combined with chemotherapy. This suggests that ABBV-400, which includes bevacizumab, might also be effective. ^{1 2 3 4 5}

How is the drug ABBV-400 different from other colorectal cancer treatments?

ABBV-400, also known as Telisotuzumab adizutecan, is unique because it is an antibody-drug conjugate, which means it combines an antibody with a drug to specifically target and kill cancer cells, potentially offering a more targeted approach compared to traditional chemotherapy that affects both healthy and cancerous cells. ^{3 4 6 7 8}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with a specific type of advanced colorectal cancer that has resisted previous treatments and shows c-Met over-expression. Participants should have measurable disease, an expected survival of at least 12 weeks, and be in good physical condition with an ECOG performance status of 0 or 1.

Inclusion Criteria

Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

Life expectancy >= 12 weeks per investigator assessment

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients, or to compounds similar to trifluridine/tipiracil

I have been treated with a c-MET targeting therapy before.

I do not have any current infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage 1

Participants receive intravenously (IV) infused ABBV-400 dose A or B

Up to 4 years

Regular visits at approved institutions

Treatment Stage 2

Participants receive the optimal dose of IV infused ABBV-400 or LONSURF oral tablets plus IV infused bevacizumab

Up to 4 years

Regular visits at approved institutions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ABBV-400
• Bevacizumab
• Trifluridine/Tipiracil

Trial Overview The study compares the effects and safety of ABBV-400 given through IV to standard oral medication LONSURF plus IV Bevacizumab in two stages. Initially, different doses of ABBV-400 are tested; then the best dose is compared to the standard treatment.

Participant Groups

Group I: Stage 2: Standard of Care (SOC) Experimental Treatment 2 Interventions

Participants will receive the SOC, as part of the approximately 4 year study duration.

Group II: Stage 2: ABBV-400 Optimal Dose Experimental Treatment 1 Intervention

Participants will receive the optimal dose of ABBV-400, as part of the approximately 4 year study duration.

Group III: Stage 1: ABBV-400 Dose B Experimental Treatment 1 Intervention

Participants will receive ABBV-400 dose B, as part of the approximately 4 year study duration.

Group IV: Stage 1: ABBV-400 Dose A Experimental Treatment 1 Intervention

Participants will receive ABBV-400 dose A, as part of the approximately 4 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

Findings from Research

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]

Combination therapy using irinotecan or oxaliplatin with infusional 5-FU and folinic acid has increased response rates to about 50% and extended median overall survival to 20 months in patients with metastatic colorectal cancer.

Monoclonal antibodies like bevacizumab and cetuximab have shown to significantly enhance treatment outcomes, with bevacizumab extending survival by over 4 months compared to chemotherapy alone, and cetuximab being effective after progression with irinotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapy options in colorectal carcinoma]. Folprecht, G., Köhne, CH.[2018]

Bevacizumab, a monoclonal antibody that blocks vascular endothelial growth factor, significantly improved response rates and survival in metastatic colorectal cancer when combined with chemotherapy, based on a randomized phase III trial.

Cetuximab, which inhibits the epidermal growth factor receptor, demonstrated a 22.5% response rate and prolonged progression-free survival in irinotecan-refractory patients, highlighting its effectiveness as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Which role do new therapeutic options play in palliative care of colorectal cancer?]. Verbeek, W., Graeven, U.[2018]

A phase III study found that the combination of atezolizumab and cobimetinib did not show improved effectiveness compared to standard therapy (regorafenib) in patients with inoperable, locally advanced, or metastatic colorectal cancer.

The overall survival for patients receiving the combination treatment was 8.9 months, slightly higher than the 8.5 months for those on standard therapy, but the response rates were very similar at 2.7% for the combination versus 2.2% for regorafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Duo Disappoints in Colorectal Cancer. [2019]

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]

Folfox4 has become the new standard treatment for colorectal cancer, particularly after the Mosaic study, while oral fluoropyrimidines like capecitabine offer effective alternatives to traditional intravenous treatments.

In stage II colon cancer, chemotherapy may not be necessary for low-risk tumors, but high-risk tumors should consider adjuvant treatments like Folfox4 or fluoropyrimidine combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of colorectal cancer]. Segura, C., Afchain, P., de Gramont, A., et al.[2018]

In a phase II trial involving 36 patients with irinotecan-refractory metastatic colorectal cancer, the combination of cetuximab, bevacizumab, and irinotecan (CBI) showed a statistically significant improvement in overall survival (OS) compared to cetuximab and irinotecan alone (CI), with median OS of 19.7 months versus 10.2 months.

Although there was no significant difference in progression-free survival (PFS) between the two treatment groups, the study suggests that further investigation into the CBI combination is warranted due to the observed benefits in overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial. Lipsyc-Sharf, M., Ou, FS., Yurgelun, MB., et al.[2022]

Infusional 5-fluorouracil (5-FU) is more effective and safer than bolus 5-FU in treating metastatic colorectal cancer (mCRC), while capecitabine offers similar efficacy with improved safety compared to 5-FU when combined with oxaliplatin.

The combination of chemotherapy with biologic agents like bevacizumab and cetuximab enhances treatment efficacy, and the approach to mCRC is shifting towards individualized therapy based on factors like KRAS mutational status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seeing the forest through the trees: a systematic review of the safety and efficacy of combination chemotherapies used in the treatment of metastatic colorectal cancer. Bekaii-Saab, T., Wu, C.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

[New therapy options in colorectal carcinoma]. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

[Which role do new therapeutic options play in palliative care of colorectal cancer?]. [2018]

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

Drug Duo Disappoints in Colorectal Cancer. [2019]

5. 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]

6. France pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of colorectal cancer]. [2018]

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

Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Seeing the forest through the trees: a systematic review of the safety and efficacy of combination chemotherapies used in the treatment of metastatic colorectal cancer. [2018]