Immunotherapy + Chemoradiation for Gastroesophageal Cancer

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

32 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment combining immunotherapy and chemoradiation for gastroesophageal cancer?

Research shows that combining radiation therapy with PD-1 inhibitors, like nivolumab, can enhance immune responses against tumors in gastroesophageal cancer. Additionally, carboplatin and paclitaxel are effective in chemoradiation for esophageal cancer, providing a viable alternative for patients who cannot tolerate other treatments. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemoradiation generally safe for treating gastroesophageal cancer?

Carboplatin and paclitaxel, when used with radiation, have been shown to be a safer alternative to other treatments for esophageal cancer, with less severe side effects. Immunotherapy with nivolumab has also been used safely in combination with these drugs for esophageal cancer. ^{5 6 7 8 9}

How is the treatment with Carboplatin, Nivolumab, Paclitaxel, Radiation, and Relatlimab different for gastroesophageal cancer?

This treatment combines chemoradiation with immunotherapy, using drugs like Nivolumab and Relatlimab, which are immune checkpoint inhibitors that help the immune system attack cancer cells. This approach is unique because it integrates multiple therapies to potentially improve outcomes for patients with locally advanced gastroesophageal cancer, compared to traditional chemotherapy alone. ^{1 4 9 10 11}

What is the purpose of this trial?

Anti-PD-1 (nivolumab) or Anti-PD1/Anti LAG-3- (relaltimab) administration in the pre-operative setting with chemoradiation will be safe and feasible in patients with resectable distal esophageal/gastroesophageal junction cancer and will change cellular and molecular characteristics of the tumor microenvironment that will improve survival.

Research Team

Vincent Lam, M.D.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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]

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]

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 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]

References

1. England 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. [2023]

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

A Phase 2 Trial Combining Pembrolizumab and Palliative Radiation Therapy in Gastroesophageal Cancer to Augment Abscopal Immune Responses. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

PD-1 and PD-L1 expression predict regression and prognosis following neoadjuvant radiochemotherapy of oesophageal adenocarcinoma. [2022]

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. England pubmed.ncbi.nlm.nih.gov

Outcome of Weekly Carboplatin-Paclitaxel-based Definitive Chemoradiation in Oesophageal Cancer in Patients Not Considered to be Suitable for Platinum-Fluoropyrimidine-based Treatment: A Multicentre, Retrospective Review. [2020]

6. New Zealand 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. [2021]

7. South Africa pubmed.ncbi.nlm.nih.gov

Carboplatin in the treatment of oesophageal cancer. [2014]

8. England 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. [2021]

9. France pubmed.ncbi.nlm.nih.gov

[News in gastrointestinal radiotherapy: The esophageal cancer]. [2022]

10. 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]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors in the Treatment of Gastroesophageal Cancer. [2022]