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

Official title

Phase II Study of Suratadenoturev (OBP-301) in Combination With Pembrolizumab in PD-L1-Negative or Immunotherapy-refractory Esophagogastric Adenocarcinoma

Overview

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.

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.

Interventions

• 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
• Drug Pembrolizumab
  400 mg IV given every 6 weeks starting on day 4 of the study and given for up to 2 years

Primary outcome measures

• Overall response rate as assessed by the RECIST v1.1 [Time frame: 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 [Time frame: 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 [Time frame: Until 30 days after the last dose of study drug]

Secondary outcome measures (4)

• Disease control rate (DCR) [Time frame: Until disease progression or death, for a maximum of approximately 2 years from start of treatment]
• Duration of response (DoR) [Time frame: Until disease progression or death, or for a maximum of approximately 2 years from start of treatment]
• Overall Survival (OS) [Time frame: 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) [Time frame: Until disease progression or death, or for a maximum of approximately 2 years from start of treatment]

Eligibility criteria

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 examined forPD-L1 assessment as defined by a Combined Positive Score (CPS), and approved commercial diagnostic assay
• If the PD-L1 CPS score is > 1, patients must have received at least one line of systemic therapy for advanced disease that includes a PD-1 or PD-L1 inhibitor.

• Patients must have clinical or radiographic disease progression on 1L therapy, or within three months of the last dose of immunotherapy
• Patients must be eligible for immunotherapy (i.e. have not had a Grade 3 or 4 immunotherapy related gastrointestinal or pulmonary toxicity, or other immune-related adverse event that excludes them from receiving future immunotherapy per PI discretion)
• If the PD-L1 CPS score is < 1, patients must not have received prior anti-PD-1 or PD-L1 therapy and must have received at least one line of systemic therapy for advanced disease.

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Weill Cornell Medicine/NewYork-Presbyterian Hospital — New York
• Abramson Cancer Center of the University of Pennsylvania — Philadelphia

Identifiers

NCT: NCT06340711 · 23-06026219

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗