Study of Suratadenoturev (OBP-301) in Combination With Pembrolizumab in Esophagogastric Adenocarcinoma

Phase II Study of Suratadenoturev (OBP-301) in Combination With Pembrolizumab in Immunotherapy Refractory Esophagogastric Adenocarcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: OBP-301; Drug: Pembrolizumab

Detailed Description

This is a phase II study of suratadenoturev (OBP-301) with pembrolizumab in advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma that has progressed on at least 1 line of prior therapy for advanced disease. Patients must have received prior immunotherapy (anti PD-1 therapy). This study will examine the addition of OBP-301 with pembrolizumab patients who are refractory to first line immunotherapy.

Patients will undergo intra-tumoral injection of OBP-301 followed 2-4 days later by the administration of pembrolizumab. The OBP-301 injection will then be repeated every two weeks for 4 planned treatments, and up to one additional optional treatment. Pembrolizumab will be administered every 6 weeks until disease progression.

The primary endpoint is objective response rate, with the target response rate of 20%, to examine the hypothesis that OBP-301 can overcome checkpoint resistance. The expected response to continuing anti-PD-1 therapy in this patient population would anticipated to be <5%. As a key secondary endpoint, the investigators will also examine duration of response and progression free survival. In a previous trial of OBP-301 and pembrolizumab in the third line setting, two patients who had a partial response are now off therapy and without evidence of disease, with a duration of response 33+ months and 20+ months. The third patient with a partial response has been on therapy for 15+ months.

This trial utilizes a Simon's two-stage Minimax design. In the first stage of the trial, 13 patients will be accrued. If there are 0 responses in these 13 patients, the study will be stopped. Otherwise, 14 additional patients will be accrued for a total of 27 patients.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Casey Owens; Phone Number: 646-962-8189; Email: cdo4001@med.cornell.edu
• Study Contact Backup: Name: Myriam Elizaire-Williams; Email: mye4001@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine/NewYork-Presbyterian Hospital
      • Contact: Casey Owens; Email: cdo4001@med.cornell.edu
      • Principal Investigator: Manish Shah, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma amenable to intra-tumoral injection (i.e. at least 1 cm in size)
• Tumor must be PD-L1 positive as defined by a combined positive score (CPS), i.e. CPS ≥ 1 by approved, commercial diagnostic assay
• Tumor must be HER2 negative as determined by a CLIA-approved laboratory

Exclusion Criteria:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 3 weeks of study Day 1.
• Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (greater than equivalent of 20 mg/day) or any other form of immunosuppressive therapy within 7 days prior to study Day 1.
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has had prior anti-cancer monoclonal antibody chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1, who has not recovered from adverse events due to a previously administered agent.
• Has a known additional malignancy within 3 years before the first OBP-301 administration that is progressing or requires active treatment, with the exception of prostate cancer controlled with androgen deprivation therapy.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Is known to have acute or chronic active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy within 2 weeks of Day 1.
• Is unable to comply with protocol procedures
• Previous severe hypersensitivity (≥ Grade 3) to any monoclonal antibody
• Has not adequately recovered from major surgery or has ongoing surgical complications.
• Has had an allogenic tissue/solid organ transplant
• Has certain uncontrolled illnesses
• Is pregnant or breastfeeding or planning to become pregnant or start breast feeding during the study time period
• Is expecting to get someone else pregnant during the study time period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OBP-301 Plus Pembrolizumab; 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.	Drug: OBP-301; 2×10(12) viral particles per injection given intratumorally every 2 weeks for a total of 4 injections starting on Day 1 of the study; Other Names: Suratadenoturev; Drug: Pembrolizumab; 400 mg IV given every 6 weeks starting on day 4 of the study and given for up to 2 years; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate as assessed by the RECIST v1.1	Overall response is defined as the sum of partial responses plus complete responses as defined by RECIST v1.1 criteria.	Until disease progression or death, or for a maximum of approximately 2 years
Number of serious adverse events (SAEs) tabulated by severity and classification per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	All SAEs will be recorded and coded by CTCAE v5 term and reported by severity and potential relatedness to study drugs	Until 90 days after the last dose of study drug
Number of adverse events (AEs) tabulated by severity and classification per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	All AEs will be recorded and coded by CTCAE v5 term and reported by severity and potential relatedness to study drugs	Until 30 days after the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Disease control rate is defined as the percentage of patients who have achieved complete response, partial response or stable disease.	Until disease progression or death, for a maximum of approximately 2 years from start of treatment
Duration of response (DoR)	Duration of response is defined as the duration that subjects who have responded to combination therapy remain without disease progression	Until disease progression or death, or for a maximum of approximately 2 years from start of treatment
Overall Survival (OS)	Overall Survival is defined as the time from registration to death due to any cause.	Until death or a maximum of 96 weeks from end of treatment (for a maximum of approximately 4 years from start of treatment)
Progression free survival (PFS)	Progression-free survival (PFS) is defined as time from registration to progression or death due to any cause. Progression is defined as radiologic progression of disease by RECIST v1.1 criteria.	Until disease progression or death, or for a maximum of approximately 2 years from start of treatment

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Merck Sharp & Dohme LLC; Oncolys BioPharma Inc
• Investigators: Principal Investigator: Manish Shah, M.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Pembrolizumab; OBP-301
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 23-06026219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No