ABBV-400 Combination Therapy for Stomach and Esophageal Cancers

(AndroMETa-GEA Trial)

Recruiting at 30 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Disqualifiers: Prior systemic therapy, Lung illnesses, 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

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for certain stomach and esophagus cancers that cannot be surgically removed or have spread. Researchers aim to evaluate the effectiveness of a new drug, ABBV-400, combined with existing cancer drugs, against these cancers. Participants will be divided into groups to determine the optimal dose of ABBV-400. This trial may suit individuals diagnosed with advanced stomach or esophageal cancer that cannot be operated on or has spread, and who have not yet received specific treatments for their condition. Regular check-ups and tests will monitor progress and side effects. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found Budigalimab to be safe for patients with other types of cancer, with most patients experiencing no severe side effects. Similarly, ABBV-400, when tested with other drugs, was generally safe for patients with advanced cancers.

Fluorouracil and Leucovorin are already approved for treating stomach and esophageal cancers. While Fluorouracil can cause side effects like nausea or tiredness, it is widely used, and its safety is well-known. Leucovorin is used alongside it to enhance effectiveness and reduce some side effects.

Although ABBV-400 and Budigalimab are still under study, earlier research suggests they are generally well-tolerated. However, since this is a Phase 2 trial, monitoring for any new side effects as the treatment progresses is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ABBV-400 because it represents a new approach to treating stomach and esophageal cancers. Unlike traditional chemotherapy options, which often include drugs like oxaliplatin, ABBV-400 is combined with budigalimab, a monoclonal antibody that may enhance the immune system's ability to fight cancer. This combination could potentially improve treatment efficacy by targeting cancer cells more precisely while minimizing damage to healthy cells. Moreover, the dose escalation and optimization strategies aim to find the most effective and least toxic dose, which could lead to better patient outcomes.

What evidence suggests that this trial's treatments could be effective for stomach and esophageal cancers?

Research has shown that ABBV-400 targets the MET gene, often linked to worse outcomes in stomach cancer. This drug has demonstrated promise by reducing levels of circulating tumor DNA, indicating potential cancer progression. In this trial, participants in certain arms will receive ABBV-400 combined with the chemotherapy drugs Fluorouracil and Leucovorin, which might enhance the effectiveness against cancer cells. Budigalimab, also part of the treatment in these arms, is a PD1 inhibitor that helps the immune system attack cancer more effectively.

In a separate arm of this trial, participants will receive the FOLFOX treatment, which includes Oxaliplatin, Fluorouracil, and Leucovorin. Studies have shown that FOLFOX can extend survival for patients with advanced stomach cancer, with an average survival time of about 11 months, indicating it can slow disease progression. Overall, the various treatment combinations in this trial aim to improve outcomes for patients with advanced stages of stomach and esophageal cancers. ^{1 3 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma that can't be surgically removed. Participants should have a good performance status (able to carry out daily activities), tested negative for HER2, and have measurable disease according to specific criteria. They must know their PD-L1 status.

Inclusion Criteria

My cancer is HER2 negative.

My cancer is advanced and cannot be removed by surgery.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of ABBV-400 in combination with a fixed dose of fluorouracil, leucovorin, and budigalimab

Part of the approximately 6-year study duration

Regular visits at an approved institution

Dose Optimization

Participants receive either FOLFOX or one of two optimized doses of ABBV-400 in combination with fluorouracil, leucovorin, and budigalimab

Part of the approximately 6-year study duration

Regular visits at an approved institution

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Budigalimab
• Fluorouracil
• Leucovorin
• Oxaliplatin

Trial Overview The study tests ABBV-400 combined with Fluorouracil, Leucovorin, and Budigalimab in two stages: finding the best dose of ABBV-400 and then comparing it with standard chemotherapy (FOLFOX). The goal is to find an effective treatment regimen for certain types of stomach cancers.

How Is the Trial Designed?

Group I: Stage 2 Arm 3: Dose Optimization Standard of Care (SOC) Experimental Treatment 4 Interventions

Participants will receive a fixed dose of leucovorin (folinic acid), fluorouracil, oxaliplatin (FOLFOX) and budigalimab as part of the approximately 6 year study duration.

Group II: Stage 2 Arm 2: Dose Optimization ABBV-400 Dose B Experimental Treatment 4 Interventions

Participants will receive ABBV-400 dose B in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.

Group III: Stage 2 Arm 1: Dose Optimization ABBV-400 Dose A Experimental Treatment 4 Interventions

Participants will receive ABBV-400 dose A in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.

Group IV: Stage 1: Dose Escalation ABBV-400 Experimental Treatment 4 Interventions

Participants will receive escalating doses of ABBV-400 in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 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

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

In a study involving 67 patients with advanced upper gastrointestinal cancers, penpulimab showed an acceptable safety profile, with 44.8% experiencing treatment-related adverse events, and only 7.5% having severe adverse events (grade ≥3).

The treatment demonstrated promising anti-tumor activity, with confirmed objective response rates ranging from 11.1% to 26.3% across different cancer types, and 85% of responders had ongoing responses at the time of the data cutoff.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penpulimab, an anti-PD1 IgG1 antibody in the treatment of advanced or metastatic upper gastrointestinal cancers. Zheng, Y., Mislang, ARA., Coward, J., et al.[2022]

In a study of 277 patients with non-metastatic esophagogastric cancer treated with the FLOT protocol, the median survival was 61 months, and the postoperative in-hospital mortality rate was low at 2%.

Recurrence after treatment predominantly occurred within the first 24 months, with gastric cancer mostly recurring as peritoneal carcinomatosis (56%) and esophageal cancer as distant organ metastasis (78%), but the site of recurrence did not affect overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern of Recurrence and Patient Survival after Perioperative Chemotherapy with 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) for Locally Advanced Esophagogastric Adenocarcinoma in Patients Treated Outside Clinical Trials. Glatz, T., Verst, R., Kuvendjiska, J., et al.[2020]

In a study of 160 Western patients with chemotherapy-refractory esophagogastric cancer, nivolumab and nivolumab plus ipilimumab showed clinically meaningful antitumor activity, with objective response rates of 12% to 24% across different treatment groups.

The treatments demonstrated encouraging long-term overall survival rates of 24% to 39% at 12 months, with a manageable safety profile, as only 17% to 47% of patients experienced severe treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. Janjigian, YY., Bendell, J., Calvo, E., et al.[2021]

In the EV-201 trial involving 125 patients with advanced urothelial carcinoma, enfortumab vedotin (EV) demonstrated a stable health-related quality of life (HRQoL) throughout treatment, with no worsening of global health status or physical functioning.

Patients who responded to EV therapy reported lower pain and fatigue levels, particularly those with bone metastases, suggesting potential improvements in symptoms alongside the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. McGregor, B., O'Donnell, PH., Balar, A., et al.[2023]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

The combination of nivolumab (an anti-PD-1 antibody) with irinotecan and a fluoropyrimidine showed a disease control rate of 73.3% in 15 patients with advanced unresectable gastroesophageal cancers, indicating potential efficacy in this challenging patient population.

The treatment was generally feasible, with a median progression-free survival of 7 months and overall survival of 13.3 months, although 33% of patients experienced dose delays or adjustments primarily due to fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. Rogers, JE., Xiao, L., Trail, A., et al.[2023]

In a meta-analysis of 1231 patients, pembrolizumab and paclitaxel showed no significant difference in effectiveness for treating advanced gastroesophageal cancer, with similar objective response rates.

Both treatments can be considered viable options for patients, as they provide comparable time to response and similar rates of partial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials. Swed, S., Shaheen, N., Hafez, W., et al.[2022]

Budigalimab, a monoclonal antibody targeting PD-1, demonstrated a safety profile similar to other PD-1 inhibitors, with the most common severe side effect being anemia in 22% of HNSCC patients and 13% of NSCLC patients.

In terms of efficacy, budigalimab showed objective response rates of 13% in head and neck squamous cell carcinoma (HNSCC) and 19% in non-small cell lung cancer (NSCLC), with median progression-free survival of 3.6 months and 1.9 months, respectively, indicating it may be a viable treatment option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma. Italiano, A., Cassier, PA., Lin, CC., et al.[2023]

The SOBIC trial demonstrated that sequential oral combination chemotherapy regimens, including S-1 with oxaliplatin and irinotecan, are effective for treating metastatic colorectal cancer (mCRC), with a median overall survival of 35.2 months among 50 patients.

The treatment was generally safe, with the most common severe side effects being sensory neuropathy (18%) and fatigue (10%), and importantly, there were no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of S-1-based sequential combination chemotherapy including oxaliplatin plus bevacizumab and irinotecan with or without cetuximab for metastatic colorectal cancer: the SOBIC trial. Nakamoto, Y., Noda, M., Mikami, R., et al.[2020]

In a phase II clinical trial, patients with gastric or esophagogastric cancer who received combination chemotherapy with rilotumumab experienced longer progression-free survival compared to those who received chemotherapy alone.

The greatest survival benefit was observed in patients with MET-positive disease, leading to the initiation of a phase III trial to further investigate this combination treatment in that specific population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rilotumumab extends PFS in gastric cancer. [2018]

In a phase III study involving 232 patients with advanced oesophageal, gastric, and pancreatic cancer, the FLP chemotherapy regimen showed comparable efficacy to the FP regimen, with similar tumor response rates and overall survival times.

The FLP regimen had a significant safety advantage, with lower rates of severe mucositis (4.5% vs. 16.4% in FP), suggesting it may be a preferable alternative for patients requiring first-line chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial). Duffour, J., Bouché, O., Rougier, P., et al.[2013]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS4202

Telisotuzumab adizutecan (ABBV-400; Temab-A) in ... MET gene amplification and increased c-Met protein expression are associated with poor survival outcomes in gastric cancer. The antibody-drug ...

2. news.abbvie.com news.abbvie.com/2025-10-13-AbbVie-to-Present-New-Data-at-ESMO-2025-Reinforcing-Leadership-in-Advancing-Targeted-Therapies-for-Solid-Tumors

AbbVie to Present New Data at ESMO 2025 Reinforcing ... In the same trial, ABBV-706 treatment also resulted in rapid clearance of circulating tumor DNA (ctDNA) and circulating tumor cells (CTC).

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-abbv-400-fluorouracil-leucovorin-and-budigalimab-for-advanced-or-metastatic-stomach-and-esophageal-cancer-patients/

Study on ABBV-400, Fluorouracil, Leucovorin, and ... It helps enhance the effectiveness of the chemotherapy, making it more potent against cancer cells. Leucovorin can also help reduce some of the side effects ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06628310

NCT06628310 | A Study to Evaluate the Adverse Events, ... The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given in combination with Fluorouracil, Leucovorin, and a ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03024-2/pdf

1439P ABBV-400, a c-Met protein- ... Conclusions: Zolbetuximab + chemotherapy continued to demonstrate statistically significant and clinically meaningful improvement in PFS and OS vs placebo +.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03000257

NCT03000257 | A Study of Budigalimab (ABBV-181) in ... This study will also evaluate the safety and tolerability of budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with ...

7. withpower.com withpower.com/trial/phase-2-adenocarcinoma-11-2024-99298

ABBV-400 Combination Therapy for Stomach and ... The safety of Budigalimab (also known as ABBV-181) was evaluated in a study for non-small cell lung cancer and head and neck cancer, showing it was generally ...