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A Study of Recombinant Vaccinia Virus in Combination With REGN2810 for Renal Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT03294083
Recruitment Status : Recruiting
First Posted : September 26, 2017
Last Update Posted : May 31, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
SillaJen, Inc.

Brief Summary:
This is a Phase 1b, open-label, multi-center, dose-escalation trial of Pexa-Vec plus REGN2810 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 REGN2810 will be determined, followed by an expansion stage. During the expansion patients will receive REGN2810 alone or in combination with Pexa-Vec, which will be administered either through intravenous (IV) or intratumoral (IT) injection.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Biological: Pexastimogene Devacirepvec (Pexa-Vec) Biological: REGN2810 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 89 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Dose-escalation Study of Pexa-Vec (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) in Combination With REGN2810 (Anti-PD-1) in Patients With Metastatic or Unresectable Renal Cell Carcinoma (RCC)
Estimated Study Start Date : May 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: 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.

REGN2810 will be administered via IV infusion every 3 weeks.

Biological: 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
Other Name: JX-594

Biological: REGN2810
REGN2810 is a monoclonal antibody to Programmed Death-1 (PD-1)

Experimental: Part 2, Pexa-Vec (IT) and REGN2810

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

REGN2810 will be administered via IV infusion every 3 weeks.

Biological: 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
Other Name: JX-594

Biological: REGN2810
REGN2810 is a monoclonal antibody to Programmed Death-1 (PD-1)

Experimental: Part 2, REGN2810

REGN2810 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. REGN2810 will continue every 3 weeks.

Biological: REGN2810
REGN2810 is a monoclonal antibody to Programmed Death-1 (PD-1)

Experimental: Part 2, Pexa-Vec (IV) and REGN2810

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

REGN2810 will be administered via IV infusion every 3 weeks.

Biological: 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
Other Name: JX-594

Biological: REGN2810
REGN2810 is a monoclonal antibody to Programmed Death-1 (PD-1)




Primary Outcome Measures :
  1. Maximum tolerated dose(MTD) / Maximum feasible dose (MFD) [ Time Frame: 36 days after first treatment ]
    MTD/MFD of Pexa-Vec administered by IV infusion in combination with REGN2810

  2. Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV REGN2810 [ Time Frame: From date of first treatment until 28 days after last treatment ]
    Safety will be determined by assessing the severity and frequency of adverse events and laboratory toxicity using CTCAE v4.03

  3. Overall response rate [ Time Frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months ]
    Evaluate anti-tumor activity and efficacy of IV or IT Pexa-Vec combined with IV REGN2810 with respect to overall response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1)


Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months ]
  2. Disease control rate [ Time Frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months ]
  3. Best radiographic response [ Time Frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months ]
  4. Overall survival [ Time Frame: Every 9 weeks, then every 12 weeks after 1 year until date of death from any cause, up to 72 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic or unresectable clear cell renal cell carcinoma (ccRCC)
  • 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: 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

Information from the National Library of Medicine

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): NCT03294083


Contacts
Contact: Stephanie Fairbairn (415) 530-4998 patient_inquiry@sillajen.com

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Jaime Merchan, MD         
Korea, Republic of
Site No. 2613 Recruiting
Pusan, Korea, Republic of
Site No. 2619 Recruiting
Pusan, Korea, Republic of
Sponsors and Collaborators
SillaJen, Inc.
Regeneron Pharmaceuticals
Investigators
Study Director: Dominic Curran, MBChB SillaJen Biotherapeutics, Inc.

Responsible Party: SillaJen, Inc.
ClinicalTrials.gov Identifier: NCT03294083     History of Changes
Other Study ID Numbers: JX594-REN026
First Posted: September 26, 2017    Key Record Dates
Last Update Posted: May 31, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by SillaJen, Inc.:
Cancer
Renal cell carcinoma
Clear cell renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Vaccinia
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Poxviridae Infections
DNA Virus Infections
Virus Diseases