Combination Therapy for Esophageal and Stomach Cancers

Recruiting at 6 trial locations

Overseen By Yelena Janjigian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Ramucirumab, Paclitaxel, Docetaxel, others

Disqualifiers: Immunodeficiency, Active tuberculosis, Active hepatitis, 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

Duration: up to 2 years

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs to treat esophageal, stomach, and gastro-esophageal junction cancers. Researchers aim to assess the effectiveness of these drugs when used together, focusing on the disease's response to each treatment. The combination includes agenT-797, an experimental treatment, Balstilimab, Botensilimab, Paclitaxel (also known as Taxol, Onxol, Abraxane), and Ramucirumab (Cyramza). This trial suits individuals with advanced cancer that has spread or cannot be surgically removed and who have shown disease progression after previous treatment. Participants must have confirmed cases of these specific cancers and meet certain health criteria. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like ramucirumab or paclitaxel recently, and you should not be on systemic steroid therapy or other immunosuppressive treatments within 7 days before starting the trial.

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

Research has shown that the treatments in this clinical trial have promising safety records from earlier studies. AgenT-797 was tested in 82 patients and did not cause severe side effects or dosage issues, indicating patients generally tolerated it well.

For balstilimab and botensilimab, studies indicate that these drugs, when used together, have a manageable safety profile. Patients did not experience new serious immune-related problems, suggesting these treatments are fairly safe.

Paclitaxel, a chemotherapy drug already used in cancer treatment, has a safety profile that can vary but is generally well-understood and commonly used for similar conditions.

Ramucirumab, approved by the FDA for other cancers, has been shown to be safe for many patients and has a good safety record in real-world use for advanced stomach cancer.

Overall, these treatments have been well-tolerated in humans. While each person's experience may differ, the available data suggests a good safety profile for the trial treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for esophageal and stomach cancers because they introduce novel mechanisms and combinations that go beyond traditional chemotherapies like fluorouracil and cisplatin. agenT-797, Balstilimab, and Botensilimab are unique because they focus on harnessing the body's immune system to fight cancer, with Balstilimab and Botensilimab being checkpoint inhibitors that help the immune system recognize and attack cancer cells more effectively. Meanwhile, Ramucirumab, an angiogenesis inhibitor, works by cutting off the blood supply tumors need to grow, offering a different approach compared to standard treatments. This combination approach aims to enhance effectiveness and potentially improve patient outcomes by targeting cancer through multiple pathways.

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

Research shows that paclitaxel, a chemotherapy drug, effectively treats advanced esophageal and stomach cancers. Studies have found that it helps manage symptoms and improve patients' quality of life. In this trial, researchers are studying Ramucirumab, which has been shown to extend the time patients live without their cancer worsening. Early data on agenT-797, which participants in this trial may receive, suggests it is safe and is being tested with other drugs to evaluate its effectiveness. The trial also examines botensilimab and balstilimab to determine if they enhance treatment effects against these cancers. Combining these treatments aims to attack cancer cells in different ways, increasing the chances of success. ^{2 4 6 7 8}

Who Is on the Research Team?

Yelena Janjigian, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with certain types of cancer affecting the stomach, esophagus, or where they join together. Specific details on who can join are not provided here, but typically participants would need to meet certain health standards and have a diagnosis that matches the trial's focus.

Inclusion Criteria

My cancer has worsened after one treatment for its advanced stage.

My cancer can be measured or evaluated for treatment response.

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

Exclusion Criteria

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have been treated with ramucirumab before.

I have had a gastrointestinal perforation or fistula.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive study treatment with agenT-797, botensilimab, balstilimab, ramucirumab, and paclitaxel. The start of each agent depends on disease impact.

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• agenT-797
• Balstilimab
• Botensilimab
• Paclitaxel
• Ramucirumab

Trial Overview The study is testing a combination of treatments: agenT-797, botensilimab, balstilimab, ramucirumab, and paclitaxel in patients with esophageal or gastric cancers. The timing of each treatment may vary based on individual patient needs.

How Is the Trial Designed?

Group I: Participants diagnoses with Esophageal, Gastric, or Gastro-esophageal Junction Cancer Experimental Treatment 5 Interventions

Participants with measurable disease and with evaluable disease as defined by RECIST v1.1 will be enrolled on this study.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Ramucirumab significantly improved overall survival in patients with advanced gastric or gastroesophageal junction adenocarcinoma, both as a monotherapy (355 patients) and in combination with paclitaxel (665 patients), with hazard ratios of 0.78 and 0.81, respectively.

The most common side effects reported were hypertension and diarrhea for the monotherapy, and fatigue, neutropenia, diarrhea, and epistaxis for the combination therapy, indicating a manageable safety profile but with notable adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ramucirumab for Gastric Cancer. Casak, SJ., Fashoyin-Aje, I., Lemery, SJ., et al.[2023]

Ramucirumab, both as a monotherapy and in combination with paclitaxel, was evaluated for treating advanced gastric cancer, but the NICE committee found it to be not cost-effective, with incremental cost-effectiveness ratios (ICERs) significantly above acceptable thresholds (e.g., £188,100 per QALY for monotherapy).

Despite showing some clinical effectiveness, neither ramucirumab alone nor in combination with paclitaxel met the criteria for cost-effectiveness as they did not provide a meaningful extension of life (less than 3 months), leading to the conclusion that these treatments could not be recommended for use in the NHS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab for Treating Advanced Gastric Cancer or Gastro-Oesophageal Junction Adenocarcinoma Previously Treated with Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Büyükkaramikli, NC., Blommestein, HM., Riemsma, R., et al.[2023]

In a phase II trial involving 30 patients with advanced esophageal cancer, the combination of paclitaxel and cisplatin resulted in a significant anti-tumor response, with 59.3% of patients showing major objective responses, including 5 complete responses.

The treatment was associated with manageable toxicity, primarily alopecia and grade 3 to 4 neutropenia in 17.9% of patients, suggesting that this regimen can be a viable option for patients with advanced esophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma of esophagus]. Huang, J., Cai, RG., Meng, PJ., et al.[2015]

The combination of ramucirumab and paclitaxel as second-line therapy in Japanese patients with metastatic gastric adenocarcinoma was found to be safe and well-tolerated, with no dose-limiting toxicities reported in a phase Ib study involving 6 patients.

Patients experienced stable disease or partial response, with a median treatment duration of approximately 12.5 weeks, indicating potential efficacy of this treatment regimen in managing advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase ib study of safety and pharmacokinetics of ramucirumab in combination with paclitaxel in patients with advanced gastric adenocarcinomas. Ueda, S., Satoh, T., Gotoh, M., et al.[2023]

In a study involving 538 patients with advanced gastric or gastroesophageal junction adenocarcinoma, ramucirumab plus paclitaxel significantly improved progression-free survival and objective response rates compared to placebo plus paclitaxel in both Japanese and Western populations.

While the combination treatment had a higher incidence of grade 3 or higher adverse events, particularly neutropenia, the overall safety profiles were similar across populations, indicating that ramucirumab plus paclitaxel is an effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer. Shitara, K., Muro, K., Shimada, Y., et al.[2023]

Ramucirumab significantly improves overall survival and progression-free survival in adults with advanced gastric or gastro-oesophageal junction adenocarcinoma, based on results from two phase III trials (REGARD and RAINBOW) involving patients treated with 8 mg/kg every 2 weeks.

The treatment is generally well-tolerated, with hypertension being the most common serious side effect, making ramucirumab a valuable second-line therapy option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab: A Review in Advanced Gastric Cancer. Greig, SL., Keating, GM.[2023]

Key chemotherapy drugs for gastroesophageal cancer include fluoropyrimidine, platinum, taxanes, and irinotecan, with concurrent chemoradiotherapy being a primary treatment approach, especially for esophageal cancer.

Targeted therapies like trastuzumab for HER2-positive gastric cancer and ramucirumab combined with paclitaxel have been shown to improve patient survival, while anti-PD-1 antibodies are now available for later-line treatment, highlighting the importance of molecular profiling in optimizing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress of chemotherapy and biomarkers for gastroesophageal cancer. Maeda, O., Ando, Y.[2020]

Esophageal cancer, particularly adenocarcinoma, is increasingly common, with over half of patients presenting with metastatic disease, making palliative chemotherapy a crucial treatment option.

Recent studies show that weekly irinotecan and cisplatin is a highly effective and less toxic regimen for treating both adenocarcinoma and squamous cell carcinoma, while paclitaxel also shows promise with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in esophageal cancer. Enzinger, PC., Ilson, DH., Kelsen, DP.[2022]

In a study of 11 patients with unresectable and recurrent gastric cancer, the combination of Ramucirumab (RAM) and paclitaxel (PTX) demonstrated efficacy, with a 90.9% disease control rate and a median overall survival of 20.8 months.

The treatment was found to be safe, with no serious adverse events reported, and it was effective across different age groups, indicating its feasibility for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical usefulness of ramucirumab plus paclitaxel for unresectable and recurrent gastric cancer. Hayase, S., Yamada, L., Ujiie, D., et al.[2023]

The combination of paclitaxel, etoposide, and cisplatin (TPE) demonstrated high efficacy in treating locally advanced gastric and gastroesophageal carcinoma, with all 22 evaluable patients responding to the treatment, including 3 complete responders and 19 partial responders.

Despite significant hematologic toxicity, including Grade 3 anemia and neutropenia in all patients, the median survival was 12.5 months, suggesting that TPE chemotherapy is a promising regimen that warrants further investigation in Phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined paclitaxel, cisplatin, and etoposide for patients with previously untreated esophageal and gastroesophageal carcinomas. Lokich, JJ., Sonneborn, H., Anderson, NR., et al.[2019]

Ramucirumab (Cyramza) is a significant advancement in the treatment of gastric cancer, targeting the vascular endothelial growth factor receptor 2 (VEGFR-2) to inhibit tumor blood supply.

Clinical studies have demonstrated that ramucirumab improves overall survival in patients with advanced gastric cancer, making it a crucial option for those with this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab (Cyramza): A Breakthrough Treatment for Gastric Cancer. Singh, AD., Parmar, S.[2020]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06251973

NCT06251973 | A Study of agenT-797 in Combination With ... Paclitaxel is widely used across multiple cancer types and is a part of standard of care treatment for advanced EG adenocarcinoma after prior treatment with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS515

A phase II study of agenT-797 (invariant natural killer T- ... This is an investigator-initiated, single-arm phase II trial in adult patients (≥18 years) with esophageal, gastric, or gastro-esophageal junction (GEJ) ...

3. investor.minktherapeutics.com investor.minktherapeutics.com/news-releases/news-release-details/first-refractory-gastric-cancer-patient-dosed-phase-2-trial

First Refractory Gastric Cancer Patient Dosed in Phase 2 ... This Phase 2 Study will evaluate the clinical safety and efficacy of the combination of agenT-797 (iNKT cells), botensilimab, a novel fc- ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS4206

STAR-221: A randomized, open-label, multicenter, phase 3 ... A randomized, open-label, multicenter, phase 3 trial of domvanalimab, zimberelimab, and chemotherapy versus nivolumab and chemotherapy in previously untreated, ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/23-361

A Phase 2 Study of AgenT-797 Plus Botensilimab, ... Researchers are assessing a combination of medications to see if they work well against upper digestive cancers.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06251973

NCT06251973 | A Study of agenT-797 in Combination With ... Ramucirumab is a part of standard of care treatment for advanced gastric cancer or GEJ adenocarcinoma, after prior treatment with fluoropyrimidine- or platinum- ...

7. nature.com nature.com/articles/s41591-024-03083-7

Botensilimab plus balstilimab in relapsed/refractory ... The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with ...

8. journals.lww.com journals.lww.com/ajg/fulltext/2024/10001/s2343_efficacy_and_safety_of_sintilimab_in.2344.aspx

S2343 Efficacy and Safety of Sintilimab in Patients With... Sintilimab shows promising efficacy and a well-tolerated safety profile. Our results suggest its potential as an innovative therapeutic option.