Pembrolizumab and Pelareorep in Treating Patients With Advanced Pancreatic Cancer

NCT03723915 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 18I01NCI-2018-02319STU00207577P30CA060553
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Adenocarcinoma; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1

  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.

  Last week of Cycle 3 (1 Cycle = 21 days)

Secondary Outcomes (6)

• Median Progression Free Survival (mPFS) by RECIST v 1.1

  Up to 2 years

• Overall Survival at One Year (12 Months)

  At 1 year

• Overall Survival (OS) at Two Years (24 Months)

  At 2 years

• Median Overall Survival (OS)

  Up to 2 years

• 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

Study Arms (1)

Treatment (pembrolizumab, wild-type reovirus)

EXPERIMENTAL

See Detailed Description

Biological: Pembrolizumab; Biological: Wild-type Reovirus

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, wild-type reovirus)

Wild-type Reovirus BIOLOGICAL

Given pelareorep IV

Also known as: Reolysin

Treatment (pembrolizumab, wild-type reovirus)

Eligibility Criteria

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

You may qualify if:

• 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 1.1.
• 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 =\< 1.
• 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.
• Hemoglobin \>= 9 g/dL, OR \>= 5.6 mmol/L with (if clinically indicated)/without transfusion or erythropoietin \[EPO\] dependency).
• Serum creatinine =\< 1.5 x upper limit of normal (ULN), OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN.
• (Note: creatinine clearance should be calculated per institutional standard.)
• Serum total bilirubin =\< 1.5 x ULN, OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN, OR =\< 5 x ULN for subjects with liver metastases.

You may not qualify if:

• 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:
• Subjects with =\< grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study.
• Patients receiving palliative radiation are eligible for this study. Palliative radiation is allowed during treatment as well. Patients with a known additional malignancy that is progressing or requires active treatment within the past 5 years are excluded. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Patients with a known active central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded.
• Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Mahalingam D, Chen S, Xie P, Loghmani H, Heineman T, Kalyan A, Kircher S, Helenowski IB, Mi X, Maurer V, Coffey M, Mulcahy M, Benson A, Zhang B. Combination of pembrolizumab and pelareorep promotes anti-tumour immunity in advanced pancreatic adenocarcinoma (PDAC). Br J Cancer. 2023 Sep;129(5):782-790. doi: 10.1038/s41416-023-02344-5. Epub 2023 Jul 13.

  PMID: 37443348 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

pembrolizumab; reolysin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Limitations and Caveats

The total accrual goal of 34 patients was not met. Stage 1 of the study did not meet the interim analysis criteria to move onto Stage 2 of the Simon 2 stage design.

Results Point of Contact

• Title: Devalingam Mahalingam MD, PhD Associate Professor, Division of Hematology and Oncology
• Organization: Northwestern University, Feinberg School of Medicine

mahalingam@nm.org

312-695-6929

Study Officials

• Devalingam Mahalingam

  Northwestern 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: October 26, 2018
• First Posted: October 30, 2018
• Study Start: November 14, 2018
• Primary Completion: December 19, 2019
• Study Completion: April 24, 2021
• Last Updated: October 5, 2022
• Results First Posted: January 20, 2021

Record last verified: 2022-09

Locations

US (1)