Phase 2 Study of Telomelysin (OBP-301) in Combination With Pembrolizumab in Esophagogastric Adenocarcinoma

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 lines of prior therapy for advanced disease.

Study Overview

• Status: Completed
• Conditions: Esophagogastric Adenocarcinoma
• Intervention / Treatment: Drug: Telomelysin

Detailed Description

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 lines of prior therapy for advanced disease. Pembrolizumab has recently received FDA approval for PD-L1 positive gastric and GEJ adenocarcinoma based on the Keynote-059 study. The efficacy of pembrolizumab monotherapy is modest in PD-L1 positive patients (defined as a combined positive score, CPS, of > 1), with only a ~15% overall response rate. This study will examine the addition of the oncolytic virus, OBP-301, administered prior to pembrolizumab in this patient population. Patients will be enrolled in a two-stage design, with 18 patients in the first stage. All patients will receive OBP-301 at 2x1012 viral particles (VP)/ tumor injection administered every two weeks x 4 injections as well as standard dose pembrolizumab 200 mg IV every 3 weeks. The tumor will be injected with OBP-301 four times (d1, d15, d29, d43). The preference is to inject the primary tumor endoscopically. Metastatic lesions may be injected on a case-by-case basis after discussion with the PI (Shah). All patients treated with OBP-301 will be eligible for the safety cohort.

Primary Endpoints:

• To examine the efficacy of OBP-301 with pembrolizumab in PD-L1 positive advanced gastric and gastroesophageal junction adenocarcinoma in the 3rd or 4th line setting, as assessed by the RECIST response rate.
• To examine the safety of multiple OBP-301 intratumoral injections in combination with pembrolizumab in advanced gastroesophageal adenocarcinoma.

Secondary Endpoint:

• To examine other measures of efficacy of the combination of OBP-301 with pembrolizumab in advanced gastric and esophageal adenocarcinoma including the disease control rate, duration of response, overall survival and progression free survival.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be willing and able to provide written informed consent for the trial.
• Be >18 years of age on the day of signing the informed consent.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Have histologically or cytologically confirmed advanced or metastatic gastroesophageal adenocarcinoma, at least 1 cm in size and amenable to intratumoral injection.
• Patient must have received at least 2 line of systemic therapy for advanced disease.
• Tumor must be PD-L1 positive, as defined by a combined positive score (CPS).
• Have one or more measurable lesions based on iRECIST.
• Be willing to provide tissue; newly obtained biopsy specimens or formalin-fixed, paraffin-embedded (FFPE) block specimens.
• Female subjects of childbearing potential have a negative urine or serum pregnancy test within 7 days prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. If a serum pregnancy test is required it can be performed on the same day as the urine pregnancy test. The serum pregnancy test must also be completed 7 days prior to enrollment. And male / female subjects of childbearing potential must agree to use an adequate method of contraception starting with signing the informed consent through 120 days after the last dose of study medication.
• Demonstrated adequate organ function as defined in following criteria. All screening labs should be performed within 14 days of enrollment. Note: Subject must not have taken transfusion, hematopoietic agent; granulocyte-colony stimulating factor (GCSF) etc., and/or oxygen supplementation within 7 days before the screening labs.
• Absolute neutrophil count (ANC)>1,000 /mm3
• Platelets>100,000 /mm3
• Hemoglobin>8.0 g/dL
• Serum total bilirubin<2.0 mg/dL
• Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT)< 3x Upper limit of normal (ULN). For subjects with liver metastases< 5x ULN.
• Serum creatinine< 2.0 mg/dL; or if serum creatinine > 2.0 mg/dL, measured or calculated creatinine/clearance >45 mL/min (Cockcroft-Gault formula).
• Life expectancy of ≥ 4 months from the first OBP-301 treatment.
• Understand the study requirements and the treatment procedures, and is willing to comply with all specified follow-up evaluations, and provides written informed consent before any study-specific tests or procedures are performed.

Exclusion Criteria:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of study Day 1.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (greater than equivalent of prednisone 20 mg/day) or any other form of immune-suppressive 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 of first injection of OBP-301 that is progressing or requires active treatment, with the exception of prostate cancer controlled with androgen deprivation therapy.
• Has received a live vaccine within 30 days of planned start of study therapy.
• Patients known to have acute or chronic active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• Has any evidence of active, non-infectious pneumonitis or interstitial lung disease requiring steroids.
• Has an active infection requiring systemic therapy within 2 weeks of Day 1.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
• Previous severe hypersensitivity to another monoclonal antibody
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/psychological incompetence, whereby in the opinion of the Investigator the patient is assessed as being unable to provide information, consent, or comply with the study requirements and procedures.
• Patients who are pregnant or breastfeeding, or expecting to conceive or father children within the projected timeframe of the study, starting from the time of the Screening Visit through 4 months (120 days) after the last OBP-301 administration. Females of childbearing potential must have a negative serum or urine pregnancy test at Screening. A female not of childbearing potential is one who has undergone bilateral oophorectomy or who has had no menses for 12 consecutive months.

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: Telomelysin (OBP-301); All patients will receive Telomelysin (OBP-301) at 2x10^12 viral particles (VP)/ tumor injection administered every two weeks x 4 injections as well as standard dose pembrolizumab 200 mg IV every 3 weeks. The tumor will be injected with OBP-301 four times (d1, d15, d29, d43). The preference is to inject the primary tumor endoscopically. Metastatic lesions may be injected on a case-by-case basis after discussion with the PI (Shah).

Drug: Telomelysin; OBP-301, the investigational product (IP) is formulated in 20 mM Tris pH 8.0, 25 mM NaCl with 2.5% glycerin, USP by volume. OBP-301 will be injected into the target tumor lesions.; Other Names: OBP-301

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate, as Assessed by Radiographic Imaging	The examination of patients with a partial or complete response is reported as the number of patients who achieved either a complete or partial response (CR + PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1, for target lesions assessed by MRI or CT Chest Abdomen and Pelvis with Contrast, a Complete Response (CR) is the disappearance of all target lesions, and a Partial Response (PR) is a ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) is defined as the sum of CR and PR.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate, as Assessed by Radiographic Imaging	Examination of subjects with stable disease, a partial response, or complete response reported as the number of participants who maintained stable disease, partial response, or complete response as per iRECIST through 1 year (SD + PR + CR). The examination of patients with a partial or complete response is reported as the number of patients who achieved either a complete or partial response (CR + PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1, for target lesions assessed by MRI or CT Chest Abdomen and Pelvis with Contrast, a Complete Response (CR) is the disappearance of all target lesions, and a Partial Response (PR) is a ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) is defined as the sum of CR and PR.	1 year
Duration of Response, as Assessed by Radiographic Imaging	Defined as the duration that subjects who have responded to combination therapy remain without disease progression. The examination of patients with a partial or complete response is reported as the number of patients who achieved either a complete or partial response (CR + PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1, for target lesions assessed by MRI or CT Chest Abdomen and Pelvis with Contrast, a Complete Response (CR) is the disappearance of all target lesions, and a Partial Response (PR) is a ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) is defined as the sum of CR and PR.	2.5 years
Overall Survival Rate, as Assessed by Survival	Defined as the number of participants who survived until 1 year from enrollment	1 year
Progression Free Survival Rate, as Assessed by Radiographic Imaging and Survival.	The number of participants who did not progress as determined by iRECIST, or die by 1 year. The examination of patients with a partial or complete response is reported as the number of patients who achieved either a complete or partial response (CR + PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1, for target lesions assessed by MRI or CT Chest Abdomen and Pelvis with Contrast, a Complete Response (CR) is the disappearance of all target lesions, and a Partial Response (PR) is a ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) is defined as the sum of CR and PR.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Tumor-immune Microenvironment, as Measured by Bulk RNA Sequencing and Single-cell RNA Sequencing.	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 immunotherapy and we will investigate how these changes impact response to treatment.	Baseline, 2 years
Change From Baseline in T-cell Response, as Measured by TCR-sequencing of Tumor Biopsies	This project will be focused on analyzing the immune landscape of individual tumors from tumor biopsies taken at baseline and on therapy. We will analyze changes associated with relapse and differences between refractory and sensitive patients. Our proposed analysis will take as input somatic mutations, raw WES reads, and raw RNA-Seq reads	Baseline, 2 years
Change From Baseline in Immune Infiltrate by Multi-parameter Flow-cytometry	This powerful approach will be utilized to characterize tumor immune cell infiltrates at baseline, following the induction of combination therapy and at the time of resection. This will be one of the first longitudinal analyses of tumor immune cell infiltrates by multi-parameter flow cytometry following immunotherapy.	Baseline, 2 years

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Oncolys BioPharma Inc
• Investigators: Principal Investigator: Manish Shah, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2019
• Primary Completion (Actual): June 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Gastric Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: 1807019403

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