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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two drugs, OBP-301 (also known as Telomelysin or Suratadenoturev) and pembrolizumab, is safe and effective for treating certain esophageal and stomach cancers. Participants will receive OBP-301 injections directly into their tumors and pembrolizumab infusions. The trial targets individuals with advanced or metastatic gastric or gastroesophageal junction cancer, whose tumors are at least 1 cm in size, PD-L1 positive, and HER2 negative. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that using OBP-301 with pembrolizumab is generally safe for patients. Studies have found that injecting OBP-301 directly into tumors is well-tolerated, with most patients not experiencing severe side effects. While some might have mild reactions, serious problems are rare.

The FDA has already approved pembrolizumab for treating other types of cancer, indicating its usual safety. However, some people might experience mild to moderate side effects, such as tiredness or a skin rash.

Overall, studies on similar conditions have used the combination of OBP-301 and pembrolizumab safely. While side effects can occur, they are mostly manageable. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for esophageal and stomach cancer?

Researchers are excited about OBP-301 plus pembrolizumab for esophageal and stomach cancer because it combines a novel approach with an established immunotherapy. Unlike traditional chemotherapy or surgery, OBP-301 is a gene therapy that specifically targets and destroys cancer cells, potentially enhancing the effectiveness of pembrolizumab, a well-known immune checkpoint inhibitor that helps the body's immune system fight cancer. This combination aims to provide a more targeted attack on tumors, which could lead to better outcomes with fewer side effects compared to conventional treatments.

What evidence suggests that this treatment might be an effective treatment for esophageal and stomach cancer?

Research shows that using OBP-301 (telomelysin) with pembrolizumab may effectively treat stomach and gastroesophageal junction cancer. In this trial, all participants will receive both OBP-301 and pembrolizumab. Earlier studies found that injecting OBP-301 directly into tumors was safe and feasible. When combined with pembrolizumab, this treatment has shown promising results, with some patients experiencing long-lasting benefits. This suggests the treatment might help manage the disease and potentially improve outcomes for people with these types of cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Manish Shah, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4052

Phase II study of telomelysin (OBP-301) in combination ... Conclusions: OBP-301 viral particle injection into the tumor is feasible and safe. OBP-301 with pembrolizumab has encouraging activity in GEA, with durable ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03921021

NCT03921021 | Phase 2 Study of Telomelysin (OBP-301) ... In this aim we will summarize the results from all patient data to assess what are the consistent changes observed in cellular composition in response to ...

3. oncolys.com oncolys.com/en/pdf/E_Press_Release_01072019.pdf

Pembrolizum “The combination of Telomelysin (OBP-301) and Pembrolizumab may improve the control of this disease. Data from this study will provide a ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-05845

Phase 2 Study of Telomelysin (OBP-301) in Combination ... This is a phase II study of OBP-301 with pembrolizumab in advanced gastric and gastroesophageal junction adenocarcinoma that has progressed on at least 2 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06340711

Study of Suratadenoturev (OBP-301) in Combination With ... 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, ...