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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03294083




Registration number
NCT03294083
Ethics application status
Date submitted
19/09/2017
Date registered
26/09/2017
Date last updated
27/10/2022

Titles & IDs
Public title
A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma
Scientific 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)
Secondary ID [1] 0 0
JX594-REN026
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pexastimogene Devacirepvec (Pexa-Vec)
Other interventions - Cemiplimab

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.
Cemiplimab will be administered via IV infusion every 3 weeks.

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.


Other 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

Other interventions: Cemiplimab
Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum tolerated dose(MTD) / Maximum feasible dose (MFD)
Timepoint [1] 0 0
36 days after first treatment
Primary outcome [2] 0 0
Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV Cemiplimab
Timepoint [2] 0 0
From date of first treatment until 28 days after last treatment
Primary outcome [3] 0 0
Overall response rate
Timepoint [3] 0 0
Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Secondary outcome [1] 0 0
Progression free survival
Timepoint [1] 0 0
Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Secondary outcome [2] 0 0
Disease control rate
Timepoint [2] 0 0
Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Secondary outcome [3] 0 0
Best radiographic response
Timepoint [3] 0 0
Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
Secondary outcome [4] 0 0
Overall survival
Timepoint [4] 0 0
Every 9 weeks, then every 12 weeks after 1 year until date of death from any cause, up to 72 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2023
Actual
Sample size
Target
Accrual to date
Final
89
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Site 2632 Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
SA5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Daegu
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Daejeon
Country [7] 0 0
Korea, Republic of
State/province [7] 0 0
Gwangju
Country [8] 0 0
Korea, Republic of
State/province [8] 0 0
Incheon
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Pusan
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seongnam-si
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seongnam
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seoul
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Suwon
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Wonju
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Yangsan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
SillaJen, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03294083
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03294083