ABBV-400 Combination Therapy for Stomach and Esophageal Cancers

(AndroMETa-GEA Trial)

Recruiting at 12 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

Trial Summary

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 Combination Therapy for Stomach and Esophageal Cancers?

The research highlights that biologic therapies, including targeted antibodies and immunomodulators, are showing promise in treating esophageal and gastric cancers. While specific data on ABBV-400 is not provided, similar treatments like trastuzumab and ramucirumab have shown effectiveness in improving survival rates in these cancers, suggesting potential for ABBV-400. ^{1 2 3 4 5}

Is ABBV-400 Combination Therapy generally safe for humans?

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 safe for patients. Additionally, 5-Fluorouracil (5-FU) and Leucovorin have been studied in combination with other drugs for gastrointestinal cancers, indicating they have an acceptable safety profile. ^{6 7 8 9 10}

What makes the ABBV-400 Combination Therapy unique for stomach and esophageal cancers?

The ABBV-400 Combination Therapy is unique because it combines Budigalimab, an immunotherapy drug, with chemotherapy agents like Fluorouracil and Leucovorin, potentially offering a novel approach by targeting the immune system alongside traditional chemotherapy to treat stomach and esophageal cancers. ^{1 2 4 11 12}

What is the purpose of this trial?

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, Leucovorin, and a programmed cell death receptor 1 (PD1) inhibitor (Budigalimab) (AFLB) to adult participants to treat locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEA). ABBV-400 and Budigalimab are investigational drugs being developed for the treatment of mGEA. Fluorouracil and Leucovorin are drugs approved for the treatment of mGEA. This study will be divided into two stages, with the first stage treating participants with increasing doses of ABBV-400 within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into groups called treatment arms where one group will receive fluorouracil, leucovorin, and oxaliplatin (FOLFOX). A further two treatment groups will receive AFLB, but with two optimized doses of ABBV-400 to allow for the best dose to be studied in the future. Approximately 180 adult participants with mGEA will be enrolled in the study in 51 sites worldwide. In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of ABBV-400 within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive FOLFOX or receive AFLB, but with one of two optimized doses of ABBV-400The study will run for a duration of approximately 6 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.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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 advanced and cannot be removed by surgery.

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

My cancer is HER2 negative.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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]

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]

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]

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 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]

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]

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 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]

References

1. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

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

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. [2023]

3. Japan 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. [2020]

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

CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. [2021]

5. United States 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. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Penpulimab, an anti-PD1 IgG1 antibody in the treatment of advanced or metastatic upper gastrointestinal cancers. [2022]

7. Germany 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. [2023]

8. Switzerland 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. [2023]

9. Greece 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). [2013]

10. Switzerland 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. [2023]

11. Switzerland 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. [2020]

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

Rilotumumab extends PFS in gastric cancer. [2018]