The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and V938 shedding in participants with advanced/metastatic or recurrent malignancies who receive V938 in combination with pembrolizumab (MK-3475). The primary objective is to determine the safety and tolerability and to identify a recommended Phase 2 dose (RP2D) of V938 administered in combination with pembrolizumab.
Due to discontinuation of V938-001, all ongoing participants who completed V938 plus pembrolizumab treatment may be enrolled in an extension study (KN587) to continue pembrolizumab monotherapy for a total of 35 cycles since the first dose in V938-001 and to be monitored as appropriate.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Participants receive V938 intratumorally in cycles 1-7. Each cycle is 21 days.
UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0002)
San Francisco, California, United States
MD Anderson Cancer Center ( Site 0001)
Houston, Texas, United States
Huntsman Cancer Institute ( Site 0004)
Salt Lake City, Utah, United States
Princess Margaret Cancer Centre ( Site 0010)
Toronto, Ontario, Canada
Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)
DLT was defined as a treatment-related adverse event (AE) including the following: Grade (Gr) 4 nonhematologic toxicity (not laboratory), Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with clinically significant bleeding, Gr 3 non-hematological AE with the exception of fatigue lasting ≤72 hours, Gr 3 nausea, vomiting, diarrhea or rash, any Gr 3 or Gr 4 nonhematologic that lead to hospitalization or abnormality persisting for \>1 week or resulting in a drug induced liver injury (DILI), febrile neutropenia Gr 3 or Gr, prolonged delay (\>2 weeks) in initiating cycle 3 (for Cohorts 1-4) or cycle 2 (for cohorts 2a-4a) due to study intervention-related toxicity, intervention-related toxicity that caused study discontinuation or missing \>1 injection of V938 as a result of drug-related AE(s) during the first 2 cycles (for cohorts 1-4) or during the first cycle (for cohort 2a-4a), Gr 5 toxicity
Time frame: Up to ~ 42 days for cohort 1, 2, 3 and 4; Up to ~ 21 days for cohorts 3a and 4a
Number of Participants Who Experienced an Adverse Event (AE)
Number of participants who experienced an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
Time frame: Up to ~ 28 months
Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Time frame: Up to ~ 25 months
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Rambam Health Care Campus-Oncology Division ( Site 0020)
Haifa, Israel
Chaim Sheba Medical Center ( Site 0021)
Ramat Gan, Israel
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions), as assessed by the investigator. In solid tumors, assessment will be based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and modified RECIST 1.1 for immune-based therapeutics (iRECIST). The percentage of participants who experience a CR or PR based on the above criteria will be presented.
Time frame: Up to ~ 33 months
Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma
The AUC0-6 for V938 RNA in plasma was calculated.
Time frame: Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.
Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma
The Cmax for V938 RNA in plasma was reported.
Time frame: Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.
Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR)
Shedding raises the possibility of transmission of oncolytic products from treated to untreated individuals. Participants treated with V938 may excrete virus via urine, respiratory tract, or GI tract after the V938 administration. The samples from the participants were collected for evaluation of virus shedding. The presence of V938 viral RNA (pfu/ml) using qRT-PCR assay was assessed in oral cavity/throat, urine, injection site, and anus to detrmine the environmental viral shedding.
Time frame: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
Number of Participants With NDV Infectivity in Excretory Tissue Samples
Participants treated with V938 may excrete virus via urine, respiratory tract, or GI tract after the V938 administration. The positive virus shedding samples that were analyzed in viral shedding were further assessed for NDV infectivity. NDV infectivity was measured by cell-based assay.
Time frame: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.