Clinical trial NCT03294083: A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma
Official title: A Phase 1b/2a Dose-escalation and Safety/Efficacy Evaluation Study of Pexa-Vec (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) in Combination With Cemiplimab (REGN2810; Anti-PD-1) in Patients With Metastatic or Unresectable Renal Cell Carcinoma (RCC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Cancer
Renal cell carcinoma
Clear cell renal cell carcinoma
Lead sponsor: SillaJen, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2017-09-26
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Maximum tolerated dose(MTD) / Maximum feasible dose (MFD)
timeFrame: 36 days after first treatment
measure: Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV Cemiplimab
timeFrame: From date of first treatment until 28 days after last treatment
measure: Overall response rate
timeFrame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Secondary outcomes:
measure: Progression free survival
timeFrame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
measure: Disease control rate
timeFrame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
measure: Best radiographic response
timeFrame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
measure: Overall survival
timeFrame: Every 9 weeks, then every 12 weeks after 1 year until date of death from any cause, up to 72 months
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Site 2644 University of California, Irvine
state: California
city: Miami
country: United States
facility: Site 2641 University of Miami
state: Florida
city: Saint Louis
country: United States
facility: Site 2643 Washington University
state: Missouri
city: Columbus
country: United States
facility: Site 2646 The Ohio State University
state: Ohio
city: Bedford Park
country: Australia
facility: Site 2632 Flinders Medical Centre
city: Daegu
country: Korea, Republic of
facility: Site 2612 Kyungpook National University Chilgok Hospital
city: Daejeon
country: Korea, Republic of
facility: Site 2616 Chungnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Site 2618 Chonnam National University Hwasun Hospital
city: Incheon
country: Korea, Republic of
facility: Site 2622 Gachon University Gil Medical Center
city: Pusan
country: Korea, Republic of
facility: Site 2613 Dong-A University Hospital
city: Pusan
country: Korea, Republic of
facility: Site 2619 Pusan National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Site 2620 Seoul National University Bundang Hospital
city: Seongnam
country: Korea, Republic of
facility: Site 2617 CHA University, CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Site 2615 Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Site 2610 Severance Hospital, Yonsei University Health System
city: Suwon
country: Korea, Republic of
facility: Site 2623 Ajou University Hospital
city: Wŏnju
country: Korea, Republic of
facility: Site 2625 Wonju Severance Christian Hospital
city: Yangsan
country: Korea, Republic of
facility: Site 2624 Pusan National University Yangsan Hospital
Study officials:
References: