ABBV-400 vs Standard Treatment for Colorectal Cancer

(AndroMETa-CRC- Trial)

Recruiting in Palo Alto (17 mi)

+50 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

Must not be taking: C-MET antibodies, ADCs

Disqualifiers: Allergy to bevacizumab, Active infection, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

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}

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.

Trial 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 (Monoclonal Antibodies)
• Bevacizumab (Monoclonal Antibodies)
• Trifluridine/Tipiracil (Anti-metabolites)

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Washington University /ID# 267872 Saint Louis, MO

University of Virginia /ID# 268108 Charlottesville, VA

St. Luke's Cancer Institute: Boise /ID# 268095 Boise, ID

The University of Texas MD Anderson Cancer Center /ID# 268098 Houston, TX

More Trial Locations

Who Is Running the Clinical Trial?

AbbVie Lead Sponsor

References

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

Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer. [2018] The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer.

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

[New therapy options in colorectal carcinoma]. [2018] The introduction of new agents improved chemotherapeutic options in colorectal cancer. Combination therapy with irinotecan or oxaliplatin, both with infusional 5-FU and folinic acid increased response rates to ca. 50% and prolongs--with effective second line therapy--median overall survival to 20 months in patients with metastatic colorectal cancer. Furthermore, the increased response rates allow neoadjuvant treatment of liver metastasis with the aim of a secondary' resection of liver metastasis. Oral 5-FU prodrugs (i.e. capecitabine) are a convenient alternative but have to prove a comparable efficacy to infusional 5-FU. The most recent studies investigated monoclonal antibodies in the treatment of metastatic colorectal cancer. The additional therapy with the VEGF-antibody bevacizumab prolongs survival by more than 4 months compared to chemotherapy alone. The EGF-receptor antibody cetuximab is an effective therapy after progression with irinotecan.

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

[Which role do new therapeutic options play in palliative care of colorectal cancer?]. [2018] Therapeutic options in the treatment of metastatic colorectal cancer have recently been expanded by the introduction of two new monoclonal antibodies: bevacizumab and cetuximab. These antibodies were the proof of principle of two exciting new antitumor strategies: antiangiogenesis and inhibition of epidermal growth factor (EGF) receptor. Bevacizumab binds to vascular endothelial growth factor and thus blocks its angiogenic effects. In a randomized phase III trial bevacizumab in combination with irinotecan + 5-fluorouracil/leucovorin (IFL) was compared to chemotherapy alone as first-line treatment. The combination showed a superior response rate, a prolonged progression-free and overall survival. Cetuximab binds to the EGF receptor and thus inhibits its activation by its natural ligand. In a randomized phase II trial irinotecan refractory patients were treated with cetuximab alone or cetuximab plus irinotecan. The combination showed a response rate of 22,5% and a prolonged progression-free survival identifying cetuximab as an important new option for this patient group.

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

Drug Duo Disappoints in Colorectal Cancer. [2019] A phase III study determined that the combination of atezolizumab and cobimetinib wasn't more effective than standard therapy in patients with inoperable, locally advanced or metastatic colorectal cancer. The overall survival for patients treated with the combination was 8.9 months, versus 8.5 months for standard-of-care regorafenib. Further, only 2.7% of patients responded to the drug duo, versus 2.2% for regorafenib.

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] The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.

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

[Adjuvant treatment of colorectal cancer]. [2018] Colorectal cancer is a real national healthy problem because of high frequency and high rate of mortality. Folfox4 is the new standard treatment since publication of Mosaic' results. Irinotecan associated with 5 fluorouracil (5FU) and leucovorin (LV) failed to demonstrate superiority over LV modulated 5FU. Oral fluoropyrimidines (capecitabine or UFT + LV) are an effective alternative to intravenous 5FU and LV. In stage II colon cancer, treatment strategies are more debated. Some data suggest that chemotherapy is not mandatory for stage II tumors low risk (T3N0 without risk factors). For stage II tumors with high risk factors (T4 or bowel obstruction, perforation, poorly differenciated tumor or,

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] Combination irinotecan and cetuximab is approved for irinotecan-refractory metastatic colorectal cancer (mCRC). It is unknown if adding bevacizumab improves outcomes.

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] Combinations of fluoropyrimidines with oxaliplatin or irinotecan plus a biologic agent are standard treatments for metastatic colorectal cancer (mCRC). Recent approvals of first-line cetuximab, second-line ziv-aflibercept, and regorafenib as salvage therapy have increased the complexity of the treatment armamentarium. To define optimal regimens, we systematically reviewed combination chemotherapy trials (N=83). Descriptive analyses focusing on fluoropyrimidine formulation, oxaliplatin vs irinotecan combinations, and compatibility with biologics indicated the following: infusional 5-fluorouracil (5-FU) yielded better efficacy and safety than bolus 5-FU. Capecitabine had similar outcomes and better safety than 5-FU with oxaliplatin but not irinotecan. First-line oxaliplatin and irinotecan appeared equivalent. Antiangiogenics, such as bevacizumab and ziv-aflibercept, and epidermal growth factor receptor-targeted monoclonal antibodies cetuximab and panitumumab further improved efficacy. The treatment landscape for mCRC has become complex, and we are approaching individualized therapy based on predictive factors, including KRAS mutational status. Appropriate administration of chemotherapy/biologic combinations is critical.