A Phase 2 Study of Pembrolizumab in Combination With Pelareorep in Patients With Advanced Pancreatic Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Pancreatic Adenocarcinoma
- Sponsor
- Northwestern University
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This phase II trial studies the side effects and how well pembrolizumab in combination with pelareorep work in treating patients with pancreatic cancer that has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. A virus, called reovirus (pelareorep), which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Giving pembrolizumab in combination with pelareorep may work better in treating patients with advanced pancreatic cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria of pembrolizumab in combination with Reovirus Serotype 3 ? Dearing Strain (pelareorep). SECONDARY OBJECTIVES: I. To determine progression free survival by RECIST v 1.1 criteria, as well as 1- year, 2-year and median overall survival with pembrolizumab in combination with pelareorep. II. To determine safety and tolerability of pembrolizumab and pelareorep when administered in combination as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. III. To determine the effects (immune response) of pembrolizumab and pelareorep when administered in combination as determined by analysis of pre-and post-treatment biopsies and blood-based immune markers. EXPLORATORY OBJECTIVES: I. To measure the overall response rate (ORR) by using Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria, for the combination of pembrolizumab and pelareorep. II. To determine progression free survival by iRECIST criteria as well as 1-year, 2-year and median overall survival with pembrolizumab in combination with pelareorep. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 32 courses in the absence of disease progression, unacceptable toxicity, development of an inter-current illness that prevents further administration of treatment, patient decides to withdraw, patients not experiencing clinical benefit in the judgment of the Investigator, or the treating investigator determines that the patient should be taken off treatment for any reason. Patients also receive Pelareorep IV over 60 minutes on days 1, 2, 3, and 8 in course 1 and on days 1 and 8 of subsequent courses. Courses repeat every 21 days for up to 24 months in the absence of disease progression, unacceptable toxicity, development of an inter-current illness that prevents further administration of treatment, patient decides to withdraw, patients not experiencing clinical benefit in the judgment of the Investigator, or the treating investigator determines that the patient should be taken off treatment for any reason. Patients who stop study therapy with stable disease (SD) or better may be eligible for up to 1 year of additional Pelareorep and pembrolizumab therapy if they progress after stopping study treatment. After completion of study treatment, patients are followed up every 3 months for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed advanced (unresectable or metastatic) pancreatic adenocarcinoma, documented objective radiographic progression and have failed or not tolerated first-line therapy.
- •Note: First-line therapy denotes systemic chemotherapy for advanced pancreatic adenocarcinoma. Only one line of therapy is permitted in this setting. Intolerant to first line therapy are patients that have developed \>= grade 3 adverse events related to first line therapy and treating physician deems continuing of systemic chemotherapy would be detrimental to patient.
- •Patients must have confirmation of an existing formalin-fixed paraffin-embedded (FPPE) tumor sample from archival tissue or from a fresh biopsy of a primary or metastatic lesion at baseline, either as a block or unstained slides for performance of correlative studies.
- •Note: Patients must undergo a fresh biopsy if archival tissue is not available.
- •Patients must have measurable disease as defined by RECIST v 1.
- •Any major surgery (except biopsies) must have occurred at least 28 days prior to first day of study treatment.
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance score =\<
- •Patients must have a life expectancy of \>= 6 months.
- •Absolute neutrophil count (ANC) \>= 1,500 /mcL (with or without growth factor use).
- •Platelets \>= 100,000 / mcL.
Exclusion Criteria
- •Patients who have had chemotherapy or radiotherapy within 4 weeks prior first day of study drug or those who have not recovered from adverse events due to agents administered more than 4 weeks from cycle 1 day 1 are not eligible.
- •Patients who have a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment are excluded.
- •Note: If patient is on high dose of steroid therapy, it needs to be brought down to \< 10 mg prednisone or equivalent for at least 7 days prior to day 1 of study treatment.
- •Patients receiving any other investigational agents for at least 4 weeks before the first dose of study treatment are not eligible.
- •Patients with a known history of active TB (Bacillus tuberculosis) are excluded.
- •Patients with a hypersensitivity to pembrolizumab or any of its excipients are excluded.
- •Patients who have had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Patients who have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 28 days prior to study day 1 or who has not recovered (i.e., NCI CTCAE version 4.03 grade =\< 1 or at baseline) from adverse events due to a previously administered agent are not eligible.
- •Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Exceptions to this criteria are:
Outcomes
Primary Outcomes
Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Time Frame: Last week of Cycle 3 (1 Cycle = 21 days)
To determine the overall response rate (ORR) by RECIST v 1.1 criteria for the combination of pembrolizumab with pelareorep. ORR is defined as the number of patients who have a complete or partial response to therapy (CR or PR). The Simon 2 stage design for this study requires 2 or more PR or CR in Stage 1 to continue accrual for Stage 2. Per RECIST v. 1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Patients who have taken one dose of either study drug, and completed the first on study scan (last week of Cycle 3) are evaluable. If a patient drops out of the study before the first scan, due to clinical progression, they are evaluable and will not be replaced.
Secondary Outcomes
- Number of Patients With Adverse Events at Grade 3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03(Up to 30 days after last dose)
- Overall Survival (OS) at Two Years (24 Months)(At 2 years)
- Immune Response Determined by Analysis of pre-and Post- Treatment Biopsies and Blood-based Immune Markers(Up to 2 years)
- Median Progression Free Survival (mPFS) by RECIST v 1.1(Up to 2 years)
- Overall Survival at One Year (12 Months)(At 1 year)
- Median Overall Survival (OS)(Up to 2 years)