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

NCT03921021 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1807019403
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Esophagogastric Adenocarcinoma

Keywords

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Disease Control Rate, as Assessed by Radiographic Imaging

  1 year

• Duration of Response, as Assessed by Radiographic Imaging

  2.5 years

• Overall Survival Rate, as Assessed by Survival

  1 year

• Progression Free Survival Rate, as Assessed by Radiographic Imaging and Survival.

  1 year

Other Outcomes (3)

• Change From Baseline in Tumor-immune Microenvironment, as Measured by Bulk RNA Sequencing and Single-cell RNA Sequencing.

  Baseline, 2 years

• Change From Baseline in T-cell Response, as Measured by TCR-sequencing of Tumor Biopsies

  Baseline, 2 years

• Change From Baseline in Immune Infiltrate by Multi-parameter Flow-cytometry

  Baseline, 2 years

Study Arms (1)

Telomelysin (OBP-301)

EXPERIMENTAL

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

Interventions

Telomelysin DRUG

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.

Also known as: OBP-301

Telomelysin (OBP-301)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Oncolys BioPharma Inc: collaborator

Study Sites (3)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Results Point of Contact

• Title: Manish Shah, MD
• Organization: Weill Cornell Medicine

mas9313@med.cornell.edu

(646) 962-6200

Study Officials

• Manish Shah, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 19, 2019
• Study Start: May 9, 2019
• Primary Completion: June 20, 2023
• Study Completion: July 20, 2023
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)