OBP-301 + Pembrolizumab for Esophageal and Stomach Cancer

Overseen By Casey Owens

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies, others

Disqualifiers: Autoimmune disease, CNS metastases, 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: 301

Duration: Up to 2 years

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug OBP-301 + Pembrolizumab for esophageal and stomach cancer?

Pembrolizumab has been shown to improve survival in patients with advanced esophageal cancer, especially when combined with chemotherapy. It is approved for use in esophageal cancer and has demonstrated promising results in clinical trials. ^{1 2 3 4 5}

Is the combination of OBP-301 and Pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda) has been shown to be safe in various studies for different types of cancer, including esophageal and gastric cancer. It has been used safely in combination with other treatments, and even in elderly patients, it has been effective and safe. However, specific safety data for the combination of OBP-301 and Pembrolizumab is not provided in the available research. ^{1 6 7 8 9}

What makes the drug combination of OBP-301 and Pembrolizumab unique for treating esophageal and stomach cancer?

The combination of OBP-301 and Pembrolizumab is unique because it combines a novel oncolytic virus (OBP-301) that selectively targets cancer cells with an immune checkpoint inhibitor (Pembrolizumab) that helps the immune system attack cancer cells. This dual approach may enhance the effectiveness of treatment compared to using Pembrolizumab alone, which has shown benefits in esophageal cancer with certain biomarkers. ^{1 3 8 10 11}

What is the purpose of this trial?

The goal of this study is to learn about of the research study drug, telomelysin (OBP-301), in combination with pembrolizumab in advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer. The main question it aims to answer is whether this combination is safe and effective in this type of cancer. Participants will receive 5 injections of OBP-301, approximately every 2 weeks. OBP-301 will be injected directly into the tumor during an esophagogastroduodenoscopy (EGD). At the same time as the injection, a tumor biopsy will be taken. Participants will also receive pembrolizumab infusions every 6 weeks until disease progression or for a maximum of two years. Pembrolizumab infusions will occur on different days than OBP-301 injections.

Research Team

Manish Shah, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults with advanced or metastatic esophagogastric adenocarcinoma, which includes certain types of cancer in the esophagus, stomach, and gastroesophageal junction. Participants should be able to undergo procedures like tumor injections during an endoscopy.

Inclusion Criteria

My tumor is PD-L1 positive with a score of 1 or higher.

My cancer in the stomach or esophagus is confirmed and can be injected.

My tumor is HER2 negative according to a certified lab test.

Exclusion Criteria

I have not taken high-dose steroids or immunosuppressants in the last 7 days.

I have not had any cancer other than prostate cancer that is under control in the last 3 years.

I have not received a live vaccine within the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 injections of OBP-301 approximately every 2 weeks and pembrolizumab infusions every 6 weeks until disease progression or for a maximum of two years

Up to 2 years

OBP-301: 5 visits (in-person), Pembrolizumab: every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose of study drug

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 4 years from start of treatment

Treatment Details

Interventions

• OBP-301
• Pembrolizumab

Trial Overview The study tests a combination of two drugs: OBP-301 (telomelysin), injected directly into the tumor every 2 weeks via endoscopy, and pembrolizumab infusions every 6 weeks. The aim is to assess safety and effectiveness against this cancer type over a maximum period of two years.

Participant Groups

Group I: OBP-301 Plus Pembrolizumab Experimental Treatment 2 Interventions

All participants will receive 4 intratumoral injections of OBP-301 with each injection occurring approximately 2 weeks apart. All participants will also receive infusions of pembrolizumab every 6 weeks until disease progression or for a maximum of 2 years.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Oncolys BioPharma Inc

Industry Sponsor

Trials

8

Recruited

120+

Findings from Research

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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 of 340 Asian patients with advanced esophageal squamous cell carcinoma (ESCC), pembrolizumab significantly improved overall survival (10.0 months) compared to chemotherapy (6.5 months), indicating its efficacy as a second-line treatment.

Patients receiving pembrolizumab experienced fewer treatment-related adverse events (71.8%) compared to those on chemotherapy (89.8%), highlighting its safety profile, especially for those with PD-L1 combined positive score (CPS) ≥1, which was identified as a predictive marker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus chemotherapy for patients with esophageal squamous cell carcinoma enrolled in the randomized KEYNOTE-181 trial in Asia. Cao, Y., Qin, S., Luo, S., et al.[2022]

The KEYNOTE-975 trial is a Phase III study designed to evaluate the effectiveness of pembrolizumab combined with chemoradiotherapy as a first-line treatment for patients with locally advanced, unresectable esophageal or gastroesophageal junction cancer.

This trial aims to improve survival outcomes, as current treatments have poor results, and will measure overall survival and event-free survival as its primary endpoints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Shah, MA., Bennouna, J., Doi, T., et al.[2021]

In a study of 55 patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with chemotherapy or radiotherapy showed favorable long-term survival outcomes, with a 12-month overall survival rate of 78.8%.

The treatment was found to be safe and manageable, with long-term adverse effects reported in only a small number of patients, indicating that pembrolizumab is a promising option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. Wang, HC., Huang, X., Chen, J., et al.[2023]

Pembrolizumab (KEYTRUDA®) has shown efficacy and safety in treating recurrent high microsatellite instability (MSI-high) gastric cancer, as demonstrated in the KEYNOTE-158 and 061 trials.

In a case study of an elderly patient with recurrent gastric cancer after surgery, pembrolizumab was successfully used as a second-line treatment, suggesting it can be a viable option for older patients in late-line chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-Term Elderly Survivor with Recurrent MSI-High Gastric Cancer Using Pembrolizumab as a Second-Line Chemotherapy]. Hamada, S., Komatsu, S., Nishiko, M., et al.[2022]

In a phase II trial involving 20 patients with locally advanced esophageal squamous cell carcinoma (ESCC), toripalimab combined with docetaxel and cisplatin showed a promising objective response rate of 70%, indicating significant efficacy as a neoadjuvant therapy.

The treatment was found to be safe, with common adverse events including leucopenia and immune dermatitis, but no treatment-related deaths or significant delays in surgery, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2). Gao, L., Lu, J., Zhang, P., et al.[2022]

Preoperative treatment with pembrolizumab combined with chemoradiotherapy was found to be safe for 20 patients with resectable esophageal squamous cell carcinoma, with a high pathologic complete response (pCR) rate of 55.6%.

Despite some patients experiencing significant adverse events, including grade III lymphopenia in 65% of cases, the treatment did not delay surgery, indicating its feasibility for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Li, C., Zhao, S., Zheng, Y., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 39 patients with locally advanced esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with neoadjuvant chemotherapy resulted in a high objective response rate of 87.2% and a disease control rate of 100%.

The treatment led to significant surgical outcomes, with a major pathological response rate of 68.2% and a complete pathological response rate of 45.5% among those who underwent radical surgery, while maintaining a manageable safety profile with only 15.4% experiencing severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: a retrospective, single-center, three-arm study. Lin, W., Huang, Y., Zhu, L., et al.[2023]

Pembrolizumab, a monoclonal antibody that inhibits PD-1, shows significant survival benefits for patients with metastatic or recurrent esophageal cancer who have a PD-L1 CPS ≥10 when used as a second-line treatment.

Current research is exploring the effectiveness of combining pembrolizumab with other treatments, which may enhance outcomes for patients with esophageal squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of esophageal cancer. Yamamoto, S., Kato, K.[2021]

References

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

2. China pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus chemotherapy for patients with esophageal squamous cell carcinoma enrolled in the randomized KEYNOTE-181 trial in Asia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. [2021]

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

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

[Long-Term Elderly Survivor with Recurrent MSI-High Gastric Cancer Using Pembrolizumab as a Second-Line Chemotherapy]. [2022]

7. China pubmed.ncbi.nlm.nih.gov

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2). [2022]

8. England pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

10. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: a retrospective, single-center, three-arm study. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of esophageal cancer. [2021]