Phase 2 Study of Telomelysin (OBP-301) in Combination With Pembrolizumab in Esophagogastric Adenocarcinoma
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|ClinicalTrials.gov Identifier: NCT03921021|
Recruitment Status : Recruiting
First Posted : April 19, 2019
Last Update Posted : May 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Esophagogastric Adenocarcinoma||Drug: Telomelysin||Phase 2|
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 1x1012 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. 41 subjects will be recruited in total for both stage 1 and 2, to achieve 37 evaluable patients.
The primary endpoint is 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 and to to examine the safety of multiple OBP-301 intratumoral injections in combination with pembrolizumab in advanced gastroesophageal adenocarcinoma.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 2 Study of Telomelysin (OBP-301) in Combination With Pembrolizumab in Esophagogastric Adenocarcinoma|
|Actual Study Start Date :||May 9, 2019|
|Estimated Primary Completion Date :||March 28, 2021|
|Estimated Study Completion Date :||March 28, 2022|
Experimental: Telomelysin (OBP-301)
All patients will receive Telomelysin (OBP-301) at 1x1012 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).
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 Name: OBP-301
- Overall response rate, as assessed by radiographic imaging [ Time Frame: 2 year ]Examination of patients with a partial response or complete response.
- Disease control rate, as assessed by radiographic imaging [ Time Frame: 1 year ]Examination of subjects with stable disease, a partial response, or complete response.
- Duration of response, as assessed by radiographic imaging [ Time Frame: 1 year ]Defined as the duration that subjects who have responded to combination therapy remain without disease progression.
- Overall survival, as assessed by survival [ Time Frame: 1 year ]Defined as the time from registration to death from any cause.
- Progression free survival, as assessed by radiographic imaging and survival. [ Time Frame: 1 year ]Defined as the time from registration to cancer progression or death due to any cause
- Change from baseline in tumor-immune microenvironment, as measured by bulk RNA sequencing and single-cell RNA sequencing. [ Time Frame: Baseline, 2 years ]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.
- Change from baseline in T-cell response, as measured by TCR-sequencing of tumor biopsies [ Time Frame: Baseline, 2 years ]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
- Change from baseline in Immune Infiltrate by multi-parameter flow-cytometry [ Time Frame: Baseline, 2 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03921021
|Contact: Sabrina Machado, RNemail@example.com|
|United States, New York|
|Weill Cornell Medical College||Recruiting|
|New York, New York, United States, 10021|
|Contact: Manish Shah, MD 646-962-6200 firstname.lastname@example.org|
|Sub-Investigator: Elizabeta Popa, M.D.|
|Sub-Investigator: Allyson Ocean, M.D.|
|Sub-Investigator: Joseph Ruggiero, M.D|
|Sub-Investigator: Doru Paul, M.D., Ph.D.|
|Principal Investigator:||Manish Shah, MD||Weill Cornell Medicine|