Immunotherapy + Chemoradiation for Gastroesophageal Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Brain metastasis, Infection, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for distal esophageal or gastroesophageal junction cancer before surgery. Researchers aim to determine if combining immunotherapy (drugs that help the immune system fight cancer) with chemoradiation (chemotherapy and radiation together) is safe and can improve survival. Participants will receive either nivolumab (Opdivo) alone or nivolumab with relatlimab, along with standard chemoradiation, which includes carboplatin (Paraplatin) and paclitaxel (Taxol). Individuals with these cancers who can eat normally and don't require tube feeding might be suitable for the trial.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you must stop them at least 14 days before the first dose, unless they are inhaled, topical, or for adrenal replacement.

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

Research has shown safety concerns when combining nivolumab with chemotherapy. In one study, 2% of patients experienced fatal side effects, such as lung inflammation. However, this combination also extended the lives of patients with stomach and gastroesophageal junction cancer.

For the combination of nivolumab and relatlimab with chemotherapy, studies found that 61% to 69% of patients experienced serious side effects. Despite these risks, some patients lived longer.

Overall, both treatment combinations have demonstrated potential benefits, but significant risks of serious side effects exist. Potential trial participants should discuss these risks with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for gastroesophageal cancer because they combine immunotherapy with traditional chemoradiation to enhance the body's ability to fight cancer. In Arm A, Nivolumab, a checkpoint inhibitor that boosts the immune system's response to cancer cells, is paired with standard chemoradiation. Arm B adds another layer by including Relatlimab, another immunotherapy that targets a different checkpoint, potentially providing a more robust immune response. This dual approach aims to improve outcomes beyond what is typically achieved with standard chemotherapy and radiation alone.

What evidence suggests that this trial's treatments could be effective for gastroesophageal cancer?

Research has shown that adding nivolumab to chemotherapy extends the lives of patients with advanced gastroesophageal cancer. One study found that patients receiving both nivolumab and chemotherapy lived longer than those receiving only chemotherapy. In this trial, participants in Arm A will receive nivolumab followed by standard chemoradiation. Studies also indicate that combining nivolumab with relatlimab is safe and effective for similar cancers. Participants in Arm B will receive this combination before standard chemoradiation. These findings suggest that using nivolumab, with or without relatlimab, alongside chemoradiation could improve outcomes for people with gastroesophageal cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Vincent Lam, M.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Adults with resectable esophageal or gastroesophageal junction cancer, who have not undergone certain treatments and do not have autoimmune diseases, active infections, or recent heart issues. Participants must meet specific health criteria like normal organ function tests, be able to undergo surgery, and agree to use contraception.

Inclusion Criteria

I can eat and maintain my weight without special feeding tubes or IV nutrition.

I had surgery that allows for my tissue to be tested for specific markers.

My cancer in the esophagus or where it meets the stomach has been confirmed by a biopsy.

Exclusion Criteria

I have an autoimmune disease, but it's not one of the exceptions listed.

My esophageal cancer is located in the middle or upper part of my esophagus.

I do not have an active infection, Hepatitis B/C, HIV/AIDS, or allergies to the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive 2 cycles of induction nivolumab or nivolumab/relatlimab

4 weeks

2 visits (in-person)

Concurrent Chemoradiation

Participants receive standard of care chemoradiation with weekly carboplatin/paclitaxel and concurrent radiation

6 weeks

6 visits (in-person)

Surgical Resection

Participants undergo surgical resection after chemoradiation

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nivolumab
• Paclitaxel
• Radiation
• Relatlimab

Trial Overview The trial is testing the safety and effectiveness of Nivolumab alone or combined with Relatlimab before chemoradiation therapy in patients preparing for surgery. It aims to see if these drugs can change tumor characteristics to improve survival rates.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 5 Interventions

Nivolumab 240mg administered IV over 30 minutes followed by relatlimab 80mg administered IV over 60 minutes on Day 1 every 2 weeks for 2 cycles and then standard of care chemoradiation (weekly carboplatin/paclitaxel and concurrent radiation).

Group II: Arm A Experimental Treatment 4 Interventions

Nivolumab 240mg administered IV over 30 minutes every 2 weeks for 2 cycles and then standard of care chemoradiation (weekly carboplatin/paclitaxel and concurrent radiation

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

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 safety run-in of the IMMUNOBIL PRODIGE 57 trial involving 20 patients, the combination of durvalumab and tremelimumab with paclitaxel resulted in a high rate of dose-limiting toxicities (50%), including serious anaphylactic reactions and other severe adverse events.

Due to the safety concerns raised by the combination therapy, the trial will proceed with only the durvalumab and tremelimumab combination, indicating that the addition of paclitaxel may not be safe for patients with advanced biliary tract carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. Boilève, A., Hilmi, M., Gougis, P., et al.[2021]

In a study of 14 patients with metastatic gastroesophageal cancer, combining palliative radiation therapy with the PD-1 inhibitor pembrolizumab resulted in an objective response rate of 28.6%, indicating potential effectiveness in this challenging cancer type.

While the combination therapy showed promising durable responses, the study did not find significant changes in PD-L1 expression that could explain the observed effects, suggesting that further research is needed to identify other biomarkers that may predict patient benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial Combining Pembrolizumab and Palliative Radiation Therapy in Gastroesophageal Cancer to Augment Abscopal Immune Responses. Chao, J., He, TF., D'Apuzzo, M., et al.[2022]

The ARION trial is investigating the efficacy of the anti-PD-L1 drug durvalumab combined with standard chemoradiotherapy (CRT) in patients with locally advanced unresectable esophageal cancer, aiming to improve progression-free survival from 50% to 68% at 12 months.

This multicenter phase II trial will also explore potential biomarkers, such as PD-L1 expression and gut microbiota, to better understand the immune response and treatment outcomes, highlighting the importance of combining immunotherapy with traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma-randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol. Modesto, A., Tougeron, D., Tremolières, P., 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]

In a safety analysis of 6 patients with locally advanced esophageal cancer, the combination of pemetrexed, carboplatin, and radiation followed by surgery showed a favorable safety profile, with only one patient experiencing a severe adverse event (grade 4 neutropenia).

The treatment resulted in promising outcomes, with one patient achieving a complete pathologic response and three showing partial responses, indicating potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. Katipamula, R., Jatoi, A., Foster, NR., et al.[2021]

Pre-operative chemotherapy with Paclitaxel-Carboplatin followed by adjuvant immunotherapy using Nivolumab has significantly improved the management of locally advanced esophageal cancer, which historically has a poor prognosis.

Current trials are exploring the effectiveness of immunotherapy for non-operable esophageal cancers, while strategies like dose escalation and combining pre-operative chemo-radiotherapy with trastuzumab have not shown benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[News in gastrointestinal radiotherapy: The esophageal cancer]. Quéro, L., Besnard, C., Guillerm, S., et al.[2022]

In a study of 11 patients with advanced oesophageal cancer, carboplatin showed a partial response in 9% of patients and minor responses in 2 cases, indicating some level of antitumor activity.

Carboplatin was well tolerated, with only one case of reversible myelosuppression reported, and no nephrotoxicity or vomiting, suggesting it may be a safer alternative to cisplatin in chemotherapy regimens for oesophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in the treatment of oesophageal cancer. Mannell, A., Winters, Z.[2014]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01601

3-Year Follow-Up of the Phase III CheckMate 649 Trial At 12.1-month minimum follow-up, nivolumab plus chemotherapy demonstrated improvement in all efficacy measures, including superior overall ...

2. opdivo.com opdivo.com/gastroesophageal-cancer/clinical-trial-results/advanced-gastric-gej-esophageal-immunotherapy-chemo

Clinical trial results for advanced gastroesophageal cancer An FDA-approved combination of immunotherapy and chemotherapy that helped people live longer compared to chemotherapy alone.

3. opdivohcp.com opdivohcp.com/efficacy/gastro

Efficacy Data for Gastroesophageal Cancers - Opdivo Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949819824000335

Safety and efficacy of first-line nivolumab plus ... At a median follow-up of 14.0 months, the median progression-free survival (PFS) and overall survival (OS) were 7.9 and 21.7 months, respectively. In patients ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11583461/

Efficacy and safety of Nivolumab in advanced gastric and ... Nivolumab, both alone and in combination with chemotherapy, improves OS and PFS in patients with advanced gastric and gastroesophageal junction cancer.

6. opdivohcp.com opdivohcp.com/safety/gastro/opdivo-chemo

Selected safety profile - Opdivo Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), ...

7. opdivo.com opdivo.com/gastroesophageal-cancer/clinical-trial-results/after-surgery-gej-esophageal-immunotherapy

Esophageal or Gastroesophageal Junction (GEJ) Cancer ... People given OPDIVO after chemoradiation and surgery had a 31% lower risk of their esophageal or GEJ cancer returning compared to people given placebo.