Neoplasm Metastasis
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Brief summary
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.
Detailed description
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.
Interventions
DRUG200 mg of pembrolizumab
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
BIOLOGICALV938
Participants receive V938 intratumorally in cycles 1-7. Each cycle is 21 days.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Dose-escalation arms (Doses A-D): Have a histologically confirmed advanced/metastatic solid tumor and have received, been intolerant to, or been ineligible for treatments known to confer clinical benefit. * For Dose Expansion Arm A: Have a histologically confirmed Stage III (unresectable) or Stage IV cutaneous melanoma and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic melanoma which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy. * For Dose Expansion Arm B: Have a histologically confirmed advanced head and neck squamous cell carcinoma (HNSCC) and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic HNSCC which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy. * For Dose Expansion Arms A and B: Have at least 1 lesion that is amenable to both intratumoral (IT) injection and biopsy and have at least 1 distant and/or discrete noninjected lesion that is measurable per RECIST 1.1 criteria. * For Dose-escalation Cohorts 2a, 3a, or 4a and Expansion Cohorts (Arms A and B) ONLY: Have baseline biopsy performed from 1 of the injectable lesions that are planned for IT injection and with tumor tissue provided. * For all arms: Have at least 1 cutaneous or subcutaneous lesion amenable to IT injection and must be measurable and meet 1 of the following criteria per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1): * A cutaneous or subcutaneous lesion ≥1 cm in longest diameter for solid tumors, or ≥1.5 cm in short axis for a nodal lesion in participants with solid tumor. The longest diameter for an injectable lesion must be ≤10 cm for both solid tumors and nodal lesions in participants with solid tumors. * Multiple coalescing, superficial lesions that in aggregate have a longest diameter of ≥1 cm and ≤10 cm. * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Show adequate organ function. * Male participants are eligible to participate if they agree to the following during the intervention period and for at least 120 days: either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR must agree to use contraception unless confirmed to be azoospermic. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: * Is not a woman of childbearing potential (WOCBP) * Is a WOCBP and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention. * HIV-infected participants must have well controlled HIV on antiretroviral therapy (ART), per study criteria.
Exclusion criteria
* Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study intervention or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study. * Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in-situ cancers. * Has clinically active central nervous system metastases and/or carcinomatous meningitis. * Has had a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study intervention or has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3). * Has an active infection requiring therapy. * Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis. * Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy. * Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or on any other form of immunosuppressive medication. * Participants with known Hepatitis B or C infections or known to be positive for hepatitis B antigen/hepatitis B virus DNA or hepatitis C antibody or RNA. * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. * Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention. * Has not fully recovered from any effects of major surgery without significant detectable infection. * Has received a live-virus vaccine within 30 days of planned treatment start. * Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days of administration of V938. * Has a history of re-irradiation for HNSCC at the projected injection site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Up to ~ 42 days for cohort 1, 2, 3 and 4; Up to ~ 21 days for cohorts 3a and 4a | 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 |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to ~ 28 months | 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 |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | Up to ~ 25 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | 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. | 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. |
| Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days. | The AUC0-6 for V938 RNA in plasma was calculated. |
| Number of Participants With NDV Infectivity in Excretory Tissue Samples | 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. | 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. |
| Objective Response Rate (ORR) | Up to ~ 33 months | 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. |
| Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days. | The Cmax for V938 RNA in plasma was reported. |
Countries
Canada, Israel, United States
Participant flow
Recruitment details
This study enrolled participants with advanced/metastatic or recurrent solid tumors.
Pre-assignment details
The study was designed/ planned to have two parts: dose escalation and expansion cohorts. Due to termination of the study, dose expansion Arm A and Arm B were not started in the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab This arm enrolled participants with advanced/metastatic or recurrent solid tumors. Participants received once every 3 weeks (Q3W) dose of 1x10\^7 PFU of V938 intratumorally on day 1 (D1) in cycles 1-7. Participants also received 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle was 21 days. | 3 |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab This arm enrolled participants with advanced/metastatic or recurrent solid tumors. Participants received once Q3W dose of 1x10\^8 PFU of V938 intratumorally on D1 in cycles 1-7. Participants also received 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle was 21 days. | 4 |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab This arm enrolled participants with advanced/metastatic or recurrent solid tumors. Participants received once Q3W dose of 3x10\^8 of V938 intratumorally on D1 in cycles 1-7. Participants also received 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle was 21 days. | 13 |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab This arm enrolled participants with advanced/metastatic or recurrent solid tumors. Participants received once Q3W dose of 5x10\^8 PFU of V938 intratumorally on D1 in cycles 1-7. Participants also received 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle was 21 days. | 5 |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab This arm enrolled participants with advanced/metastatic or recurrent solid tumors. Participants received once Q3W dose of 3x10\^8 PFU of V938 on D1 intratumorally in cycles 1-7. Participants also received 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle was 21 days. | 5 |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab This arm enrolled participants with advanced/metastatic or recurrent solid tumors. Participants received once Q3W dose of 5x10\^8 PFU of V938 intratumorally on D1 in cycles 1-7. Participants also received 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle was 21 days. | 5 |
| Dose Expansion Arm A, Melanoma This arm was intended enroll participants with diagnosis of stage III (unresectable) and Stage IV melanoma (any line of therapy). Participants were intended to receive V938 at the recommended Phase 2 dose, determined by analysis of the dose 1x10\^7 PFU to 3x10\^8 PFU arms, intratumorally on D1 in cycles 1-7. Participants were also intended to receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle was 21 days. Due to study termination, this arm was not started in the study. | 0 |
| Dose Expansion Arm B, HNSCC This arm was intended to enroll participants with a diagnosis of advanced/metastatic head and neck squamous cell carcinoma (HNSCC). Participants were intended to receive V938 at the recommended Phase 2 dose, determined by analysis of the dose 1x10\^7 PFU to 3x10\^8 PFU arms, intratumorally in cycles 1-7. Participants were also intended to receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle was 21 days. Due to study termination, this arm was not started in the study. | 0 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 4 | 7 | 0 | 3 | 1 | 0 | 0 |
| Overall Study | Not treated-randomization error | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 2 | 5 | 1 | 4 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Total | Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Dose Expansion Arm B, HNSCC | Dose Expansion Arm A, Melanoma |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 73.3 Years STANDARD_DEVIATION 5.1 | 60.3 Years STANDARD_DEVIATION 10.9 | 53.2 Years STANDARD_DEVIATION 13 | 67.8 Years STANDARD_DEVIATION 11.7 | 67.6 Years STANDARD_DEVIATION 9.2 | 61.7 Years STANDARD_DEVIATION 11.4 | 55.3 Years STANDARD_DEVIATION 4.2 | — | — |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 0 | 2 Participants | 6 Participants | 2 Participants | 2 Participants | 2 Participants | 14 Participants | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 1 | 1 Participants | 7 Participants | 3 Participants | 3 Participants | 3 Participants | 21 Participants | 4 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 12 Participants | 3 Participants | 5 Participants | 5 Participants | 32 Participants | 4 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 13 Participants | 4 Participants | 5 Participants | 5 Participants | 34 Participants | 4 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 4 Participants | 1 Participants | 3 Participants | 17 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 7 Participants | 1 Participants | 4 Participants | 2 Participants | 18 Participants | 4 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 4 / 4 | 8 / 13 | 0 / 5 | 3 / 5 | 1 / 5 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 2 / 3 | 4 / 4 | 12 / 12 | 5 / 5 | 5 / 5 | 5 / 5 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 3 | 2 / 4 | 2 / 12 | 1 / 5 | 2 / 5 | 4 / 5 | 0 / 0 | 0 / 0 |
Outcome results
Primary
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
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention. Due to termination of the study, dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 2 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 1 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 Participants |
Primary
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
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention. Due to termination of the study, dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 12 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
Primary
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
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention and who met the criteria for DLT evaluability. Due to termination of the study, dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 1 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 1 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) | 0 Participants |
Secondary
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.
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol, AUC0-6 was calculated for the participants who had concentration values. Due to termination of the study, data were not collected for participants in Cohort 4a Cohort 4a: V938 5x10\^8 PFU + pembrolizumab and dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 1249 Hours*pfu/mL | Geometric Coefficient of Variation 157.1 |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 46.2 Hours*pfu/mL | Geometric Coefficient of Variation 14.6 |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 753 Hours*pfu/mL | — |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 314 Hours*pfu/mL | Geometric Coefficient of Variation 307.1 |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 55.5 Hours*pfu/mL | Geometric Coefficient of Variation 1007.4 |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 158 Hours*pfu/mL | Geometric Coefficient of Variation 64.7 |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 191 Hours*pfu/mL | Geometric Coefficient of Variation 104.3 |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 354 Hours*pfu/mL | Geometric Coefficient of Variation 313.1 |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 119 Hours*pfu/mL | Geometric Coefficient of Variation 239.8 |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 2520 Hours*pfu/mL | — |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 867 Hours*pfu/mL | — |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 1040 Hours*pfu/mL | — |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 95.7 Hours*pfu/mL | Geometric Coefficient of Variation 107.1 |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 430 Hours*pfu/mL | Geometric Coefficient of Variation 79.5 |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 24.4 Hours*pfu/mL | Geometric Coefficient of Variation 3.9 |
Secondary
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.
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol, Cmax was calculated for the participants who had concentration values. Due to termination of the study, data were not collected for participants in Cohort 4a Cohort 4a: V938 5x10\^8 PFU + pembrolizumab and dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 65.6 pfu/mL | Geometric Coefficient of Variation 104.7 |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 11.2 pfu/mL | Geometric Coefficient of Variation 14.4 |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 66.4 pfu/mL | Geometric Coefficient of Variation 291.2 |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 85.5 pfu/mL | Geometric Coefficient of Variation 176 |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 15.1 pfu/mL | Geometric Coefficient of Variation 951.6 |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 51.3 pfu/mL | Geometric Coefficient of Variation 77.4 |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 57.6 pfu/mL | Geometric Coefficient of Variation 78.5 |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 55.6 pfu/mL | Geometric Coefficient of Variation 593.8 |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 31.0 pfu/mL | Geometric Coefficient of Variation 255.9 |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 595 pfu/mL | — |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 97.9 pfu/mL | Geometric Coefficient of Variation 204.1 |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 235 pfu/mL | Geometric Coefficient of Variation 17.7 |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 8 | 10.1 pfu/mL | Geometric Coefficient of Variation 1259 |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 1 Day 1 | 26.6 pfu/mL | Geometric Coefficient of Variation 3122.3 |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma | Cycle 2 Day 1 | 8.40 pfu/mL | Geometric Coefficient of Variation 37.9 |
Secondary
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.
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention and had available data. V938 excretion based on infectivity was calculated for the participants who had concentration values. Due to termination of the study, dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Urine | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Oral cavity/throat | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Injection site | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With NDV Infectivity in Excretory Tissue Samples | Anal swab | 0 Participants |
Secondary
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.
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention and had available data. Per protocol, V938 excretion was calculated for the participants who had concentration values. Due to termination of the study, dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 0 Participants |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 3 Participants |
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 4 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 1 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 1 Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 10 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 0 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 0 Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 0 Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Dose Expansion Arm A, Melanoma | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Urine | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Oral cavity/throat | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Anal swab | 0 Participants |
| Dose Expansion Arm B, HNSCC | Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR) | Injection site | 0 Participants |
Secondary
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
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study intervention. Due to termination of the study, dose expansion Arm A and Arm B were not started in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: V938 1x10^7 Plaque-forming Units (PFU) + Pembrolizumab | Objective Response Rate (ORR) | 0.0 Percentage of Participants |
| Cohort 2: V938 1x10^8 PFU + Pembrolizumab | Objective Response Rate (ORR) | 0.0 Percentage of Participants |
| Cohort 3: V938 3x10^8 PFU + Pembrolizumab | Objective Response Rate (ORR) | 0.0 Percentage of Participants |
| Cohort 4: V938 5x10^8 PFU + Pembrolizumab | Objective Response Rate (ORR) | 0.0 Percentage of Participants |
| Cohort 3a: V938 3x10^8 PFU + Pembrolizumab | Objective Response Rate (ORR) | 0.0 Percentage of Participants |
| Cohort 4a: V938 5x10^8 PFU + Pembrolizumab | Objective Response Rate (ORR) | 40.0 Percentage of Participants |