A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma

NCT ID: NCT03294083

Last Updated: 2022-10-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-07
• Study Completion Date: 2023-11-30

Brief Summary

This is a Phase 1b/2a, open-label, multi-center, dose-escalation and safety/efficacy evaluation trial of Pexa-Vec plus Cemiplimab in patients with metastatic or unresectable renal cell carcinoma (RCC). The trial consists of a dose-escalation stage, where the maximum feasible dose of Pexa-Vec in combination with Cemiplimab will be determined, followed by an expansion stage. During the expansion patients will receive Cemiplimab alone or in combination with Pexa-Vec, which will be administered either through intravenous (IV) or intratumoral (IT) injection.

Conditions

Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1, Dose escalation

Pexa-Vec will be administered via IV infusion at a dose of 3 x 10^8 pfu once per week for 4 treatments. Based on the occurrence of dose-limiting toxicities, patients may subsequently be enrolled to receive Pexa-Vec on the same schedule at a dose of 1 x 10^9 pfu.

Cemiplimab will be administered via IV infusion every 3 weeks.

Group Type: EXPERIMENTAL

Pexastimogene Devacirepvec (Pexa-Vec)

Intervention Type: BIOLOGICAL

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells

Cemiplimab

Intervention Type: BIOLOGICAL

Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab

Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments.

Cemiplimab will be administered via IV infusion every 3 weeks.

Group Type: EXPERIMENTAL

Pexastimogene Devacirepvec (Pexa-Vec)

Intervention Type: BIOLOGICAL

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells

Cemiplimab

Intervention Type: BIOLOGICAL

Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

Part 2-Arm B, Cemiplimab

Cemiplimab will be administered via IV infusion every 3 weeks.

At disease progression, Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. Cemiplimab will continue every 3 weeks.

Group Type: EXPERIMENTAL

Pexastimogene Devacirepvec (Pexa-Vec)

Intervention Type: BIOLOGICAL

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells

Cemiplimab

Intervention Type: BIOLOGICAL

Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab

Pexa-Vec will be administered via IV infusion once per week for 4 treatments.

Cemiplimab will be administered via IV infusion every 3 weeks.

Group Type: EXPERIMENTAL

Pexastimogene Devacirepvec (Pexa-Vec)

Intervention Type: BIOLOGICAL

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells

Cemiplimab

Intervention Type: BIOLOGICAL

Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab

Pexa-Vec will be administered via IV infusion once per week for 4 treatments.

Cemiplimab will be administered via IV infusion every 3 weeks.

Group Type: EXPERIMENTAL

Pexastimogene Devacirepvec (Pexa-Vec)

Intervention Type: BIOLOGICAL

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells

Cemiplimab

Intervention Type: BIOLOGICAL

Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

Interventions

Pexastimogene Devacirepvec (Pexa-Vec)

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells

Intervention Type: BIOLOGICAL

Cemiplimab

Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)

Intervention Type: BIOLOGICAL

Other Intervention Names

JX-594

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed metastatic or unresectable clear cell renal cell carcinoma (ccRCC)
• Part 2 Arm D ONLY: Patients must be refractory to anti PD-1 or anti-PD-L1 (either as monotherapy or in-combination with other approved checkpoint inhibitors or targeted therapies according to their approved label) and patients must meet all of the following criteria:

1. Received treatment of approved anti PD-1 or anti-PD-L1 (dosed per label of the country providing the clinical site) for at least 6 weeks. History of anti-PD-L1 only is not allowed.

2. Progressive disease after anti PD-1 or anti-PD-L1 will be defined according to RECIST 1.1. The initial evidence of progressive disease is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented progressive disease, in the absence of rapid clinical progression. (This determination is made by the Investigator; the Sponsor will collect imaging scans for retrospective analysis. Once progressive disease is confirmed, the initial date of progressive disease documentation will be considered the date of disease progression).

3. Documented disease progression within 12 weeks of the last dose of anti PD-1 or anti-PD-L1. Patients who were re-treated or on maintenance with anti-PD-1 or anti-PD-L1 will be allowed to enter the study as long as there is documented progressive disease within 12 weeks of the last treatment date.

• Naive to systemic therapy for RCC or have progressed after, or were intolerant of, prior systemic therapy.
• Measurable disease based on RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Karnofsky performance status of 70-100
• Age ≥20 years old (or appropriate age of consent for the region)
• Adequate hematological, hepatic, and renal function

Exclusion Criteria

• Known significant immunodeficiency due to underlying illness (e.g., human immunodeficiency virus [HIV] / acquired immune deficiency syndrome [AIDS]) and/or immune-suppressive medication including high-dose corticosteroids
• Part 2 only: Arm A,B,C: Prior treatment with any anti-cancer immunotherapy, including therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (prior IL-2 or interferon allowed) . For Part 1: patients are excluded if they were intolerant to anti-PD-1 or anti-PD-L1 targeted therapies
• Major surgery within 4 weeks of study treatment (minor surgical procedures are allowed)
• Ongoing severe inflammatory skin condition requiring prior medical treatment
• History of eczema requiring prior medical treatment
• Tumor(s) invading a major vascular structure (e.g., carotid artery) or other key anatomical structure (e.g., pulmonary airway) OR viable central nervous system malignancy
• Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions.
• Symptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months.
• Asymptomatic cardiovascular disease (current or past history) unless cardiology consultation and clearance has been obtained for study participation.
• Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all Pexa-Vec treatments
• Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any Pexa-Vec dose
• Known active Hepatitis B or Hepatitis C

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

SillaJen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Site 2644 University of California, Irvine

Irvine, California, United States

Site 2641 University of Miami

Miami, Florida, United States

Site 2643 Washington University

St Louis, Missouri, United States

Site 2646 The Ohio State University

Columbus, Ohio, United States

Site 2632 Flinders Medical Centre

Bedford Park, , Australia

Site 2612 Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site 2616 Chungnam National University Hospital

Daejeon, , South Korea

Site 2618 Chonnam National University Hwasun Hospital

Gwangju, , South Korea

Site 2622 Gachon University Gil Medical Center

Incheon, , South Korea

Site 2613 Dong-A University Hospital

Pusan, , South Korea

Site 2619 Pusan National University Hospital

Pusan, , South Korea

Site 2617 CHA University, CHA Bundang Medical Center

Seongnam, , South Korea

Site 2620 Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site 2615 Korea University Anam Hospital

Seoul, , South Korea

Site 2610 Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site 2623 Ajou University Hospital

Suwon, , South Korea

Site 2625 Wonju Severance Christian Hospital

Wŏnju, , South Korea

Site 2624 Pusan National University Yangsan Hospital

Yangsan, , South Korea

Countries

United States; Australia; South Korea

Other Identifiers

JX594-REN026

Identifier Type: -

Identifier Source: org_study_id