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, tolerability, and efficacy in participants with advanced/metastatic or recurrent malignancies who receive gebasaxturev (V937) in combination with pembrolizumab (MK-3475). The primary objective for Part 1 is to evaluate the objective response rate, and the primary objective for Part 2 is to determine the safety and tolerability of gebasaxturev administered in combination with pembrolizumab. With Amendment 4, this study will be terminated once all participants who have completed or discontinued gebasaxturev treatment and are only receiving pembrolizumab may be enrolled in a pembrolizumab extension study, if available, to continue pembrolizumab monotherapy for up to 35 cycles from first pembrolizumab dose on V937-013.
Interventions
BIOLOGICALGebasaxturev
Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.
DRUGPembrolizumab
Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Locally-advanced disease that is not amenable to surgery or radiation, or Stage IV advanced/metastatic solid tumor malignancies * Histologically- or cytologically-confirmed diagnosis of an advanced/metastatic solid tumor. * Measurable disease by RECIST 1.1 criteria as assessed by investigator. Target lesions in a previously irradiated area will be considered measurable if progression has been demonstrated in such lesions * Submitted a baseline tumor sample for analysis. Participants enrolling in Part 2 Cohorts D-F may enroll without submitting a tumor sample if all other enrollment criteria are met. * Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale obtained within 72 hours prior to the first dose of study intervention * If participant has known human immunodeficiency virus (HIV)-positive disease, participant must have well-controlled HIV on antiretroviral therapy (ART), per study criteria. * 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: 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. * Female participants are eligible to participate if not pregnant or breastfeeding, and at least one 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. * Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Part 1, All Cohorts: participants must have at least one injectable lesion amenable to injection and/or biopsy. * Part 1, Cohort A: * Locally recurrent, inoperable OR metastatic breast cancer treated with at least 1 prior line of therapy in the metastatic setting with skin involvement and/or subcutaneous lesions or accessible lymph nodes amenable to local injection. An exception would be allowed for participants who are not eligible to receive chemotherapy. * Diagnosis of triple-negative breast cancer (estrogen receptor, progesterone receptor, and HER2-receptor negative status) * Part 1, Cohort B: * Histologically confirmed advanced or metastatic head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx considered incurable and/or treated with no more than 1 previous line of therapy * Tumors must be PD-L1+ * Documentation of HPV status for oropharyngeal cancers. Other HNSCC subtypes may submit HPV testing, but is not required. * Part 1, Cohort C: * Histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy * Recurrent/metastatic disease only: Has metastatic disease defined as disseminated disease distant from the initial/primary site of diagnosis and/or with a history of locally-recurrent disease previously treated with surgery and/or radiotherapy, which is now incurable * Locally-advanced disease only: Must be ineligible for surgical resection per study criteria, and must have received prior radiation therapy to the index site or deemed ineligible for radiation therapy * Part 2, Solid Tumors+Liver Metastases Dose Level 1-3 arms: * Histologically-confirmed advanced/metastatic solid tumor that has progressed on all treatment known to confer clinical benefit * Metastatic liver lesion(s) not exceeding one-third of the total liver volume AND a minimum of one injectable liver lesion * Part 2, Cohort D: * Advanced hepatocellular carcinoma (HCC) following progression on, or intolerance to, sorafenib or lenvatinib with no curative options * Diagnosis of HCC confirmed by radiology, histology, or cytology * Child-Pugh Class A score * If a participant has a history of hepatitis C virus (HCV) infection, then the participant must have been successfully treated for this condition * Controlled (treated) hepatitis B participants will be allowed if they meet protocol-specified criteria * Participants who are anti-hepatitis B core (HBc) positive, negative for hepatitis B surface antigen (HBsAg), negative or positive for anti-hepatitis B surface (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV anti-viral prophylaxis * Part 2, Cohort E: * Histologically- or cytologically-confirmed diagnosis of locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma * Received at least one prior line of therapy that includes a platinum/fluoropyrimidine doublet or triplet regimen * Had proven clinical progression 6 months following (or during) last dose of adjuvant or neo-adjuvant therapy * Human epidermal growth factor receptor 2 (HER2) negative status; or, those with HER2 positive status AND documented disease progression on a prior regimen containing trastuzumab
Exclusion criteria
* Chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to first dose of study intervention, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better * If major or minor surgery was performed at/near the area being considered for injection, participant must be recovered from toxicity and/or complications of intervention * If participant has had injection or radiation therapy, participant must be recovered from toxicity and/or complications of intervention * History of second malignancy, unless potentially curative treatment has been completed with no further evidence of disease for ≥5 years. * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if lesions are radiologically stable. * Active infection requiring therapy, except HIV criteria as stated above, and HBV and HCV criteria for HCC cohort as stated above * History of interstitial lung disease * History of noninfectious pneumonitis requiring active steroid therapy or ongoing pneumonitis * Active autoimmune disease that required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy * Known Hepatitis B or C infections or known to be positive for HBsAg/HBV deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA) * History of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Known hypersensitivity to gebasaxturev and/or pembrolizumab or any of their excipients * Received prior therapy with anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1) agents, Talimogene Laherparepvec (T-VEC), or any other oncolytic virus therapies * Received a live or live-attenuated vaccine within 30 days prior to first dose of study intervention. Administration of killed vaccines is allowed. * 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 * Part 2, Cohort D: * Has had esophageal or gastric variceal bleeding within the last 6 months * Has had clinically diagnosed hepatic encephalopathy in the 6 months prior to initiation of study intervention * Part 2, Cohort E: * Squamous cell or undifferentiated gastric cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator | Up to approximately 30 months | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
| Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | Cycle 1 (28-day cycle) | The following toxicities during DLT evaluation period were considered a DLT, if assessed by investigator to be possibly, probably, or definitely related to treatment: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 3 thrombocytopenia (if associated with clinically significant bleeding) or any grade febrile neutropenia; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for \>1 week); drug-related toxicity that causes a \>2 week delay in Cycle 2 initiation; drug-related toxicity that causes treatment discontinuation or missed dosage of gebasaxturev; or Gr 5 toxicity. Per protocol, only the participants in Part 2 were analyzed in this outcome measure. |
| Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to approximately 29 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure. |
| Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 10 months | An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator | Up to approximately 30 months | PFS was defined as the time from first dose of study treatment to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurs first as assessed by investigator. Per iRECIST, iCPD was defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
| DOR Per iRECIST as Assessed by Investigator | Up to approximately 30 months | For participants who demonstrated confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST, DOR was defined as the time from the first documented CR or PR, or iCR or an iPR, as assessed by investigator, until progressive disease or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
| Part 1: Number of Participants Who Experienced One or More AEs | Up to approximately 30 months | An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
| Overall Survival (OS) | Up to approximately 30 months | OS was defined as the time from first dose of study intervention to death due to any cause. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
| Part 2: ORR Per RECIST 1.1 as Assessed by Investigator | Up to approximately 29 months | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 2 were analyzed for this outcome measure. |
| ORR Per iRECIST as Assessed by Investigator | Up to approximately 30 months | ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-based Complete Response (iCR: Disappearance of all target lesions) or an immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST as assessed by investigator. |
| Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 23 months | An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
| Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator | Up to approximately 30 months | PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by investigator. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator | Up to approximately 30 months | For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure. |
Countries
Canada, France, Germany, Hungary, Israel, Italy, Japan, Norway, Peru, Poland, Portugal, Spain, Taiwan, United States
Participant flow
Pre-assignment details
76 participants were allocated and 75 participants received study intervention. The study was terminated before any participants were enrolled into Cohorts D and E.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer Participants with triple-negative breast cancer (TNBC) solid tumors received 3 X 10\^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days. | 22 |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Participants with head and neck squamous cell carcinoma (HNSCC) solid tumors received 3 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days. | 14 |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Participants with cutaneous squamous cell carcinoma (cSCC) solid tumors received 3 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days. | 17 |
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases Participants with solid tumors with liver metastases received 3 X 10\^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days. | 6 |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases Participants with solid tumors with liver metastases received 1 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days. | 3 |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases Participants with solid tumors with liver metastases received 3 X 10\^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days. | 14 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Allocated in error without study intervention | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 17 | 8 | 8 | 5 | 2 | 7 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 4 | 6 | 8 | 0 | 1 | 7 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 2 Dose Level 2, Solid Tumors + Liver Metastases | Part 2 Dose Level 3, Solid Tumors + Liver Metastases | Total | Part 1, Cohort A: Triple-Negative Breast Cancer | Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Part 2 Dose Level 1, Solid Tumors + Liver Metastases |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 8.3 | 57.8 years STANDARD_DEVIATION 14.1 | 62.4 years STANDARD_DEVIATION 15.7 | 55.5 years STANDARD_DEVIATION 11.5 | 59.7 years STANDARD_DEVIATION 13.1 | 80.6 years STANDARD_DEVIATION 12.8 | 54.7 years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 11 Participants | 65 Participants | 18 Participants | 14 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 7 Participants | 0 Participants | 0 Participants | 4 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 |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 14 Participants | 0 Participants | 7 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 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 | 2 Participants | 2 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 5 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 8 Participants | 55 Participants | 20 Participants | 7 Participants | 14 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 45 Participants | 22 Participants | 2 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 31 Participants | 0 Participants | 12 Participants | 11 Participants | 3 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 18 / 22 | 8 / 14 | 8 / 17 | 5 / 6 | 2 / 3 | 7 / 14 |
| other Total, other adverse events | 18 / 21 | 14 / 14 | 17 / 17 | 6 / 6 | 2 / 3 | 14 / 14 |
| serious Total, serious adverse events | 4 / 21 | 8 / 14 | 6 / 17 | 4 / 6 | 1 / 3 | 3 / 14 |
Outcome results
Primary
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
The following toxicities during DLT evaluation period were considered a DLT, if assessed by investigator to be possibly, probably, or definitely related to treatment: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 3 thrombocytopenia (if associated with clinically significant bleeding) or any grade febrile neutropenia; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for \>1 week); drug-related toxicity that causes a \>2 week delay in Cycle 2 initiation; drug-related toxicity that causes treatment discontinuation or missed dosage of gebasaxturev; or Gr 5 toxicity. Per protocol, only the participants in Part 2 were analyzed in this outcome measure.
Time frame: Cycle 1 (28-day cycle)
Population: The analysis population included all allocated participants in Part 2 who received at least 1 dose of study treatment who met the criteria for DLT evaluability (e.g. finished Cycle 1 without a DLT or experienced a DLT in Cycle 1). Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
Primary
Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Population: The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator | 0.0 Percentage of Participants |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator | 35.7 Percentage of Participants |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator | 64.7 Percentage of Participants |
Primary
Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
Time frame: Up to approximately 10 months
Population: The analysis population included all allocated participants in Part 2 who received study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases | Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE | 0 Participants |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases | Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE | 0 Participants |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases | Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE | 1 Participants |
Primary
Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
Time frame: Up to approximately 29 months
Population: The analysis population included all allocated participants in Part 2 who received study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases | Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs) | 6 Participants |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases | Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs) | 2 Participants |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases | Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs) | 14 Participants |
Secondary
DOR Per iRECIST as Assessed by Investigator
For participants who demonstrated confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST, DOR was defined as the time from the first documented CR or PR, or iCR or an iPR, as assessed by investigator, until progressive disease or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Population: The analysis population consisted of all allocated participants in Part 1 who experienced a confirmed response (CR, PR, iCR or iPR) with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention. No participants in Part 1, Cohort A were eligible for analysis. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | DOR Per iRECIST as Assessed by Investigator | NA Months |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | DOR Per iRECIST as Assessed by Investigator | NA Months |
Secondary
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Population: The analysis population consisted of all allocated participants in Part 1 who experienced a confirmed CR or PR with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention. No participants in Part 1, Cohort A were eligible for analysis. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator | NA Months |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator | NA Months |
Secondary
ORR Per iRECIST as Assessed by Investigator
ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-based Complete Response (iCR: Disappearance of all target lesions) or an immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST as assessed by investigator.
Time frame: Up to approximately 30 months
Population: The analysis population consisted of all participants with a baseline scan that demonstrated measurable disease and who were administered at least one dose of study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | ORR Per iRECIST as Assessed by Investigator | 0.0 Percentage of Participants |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | ORR Per iRECIST as Assessed by Investigator | 42.9 Percentage of Participants |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | ORR Per iRECIST as Assessed by Investigator | 64.7 Percentage of Participants |
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases | ORR Per iRECIST as Assessed by Investigator | 16.7 Percentage of Participants |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases | ORR Per iRECIST as Assessed by Investigator | 0.0 Percentage of Participants |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases | ORR Per iRECIST as Assessed by Investigator | 0.0 Percentage of Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from first dose of study intervention to death due to any cause. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Population: The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | Overall Survival (OS) | 7.5 Months |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Overall Survival (OS) | 11.8 Months |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Overall Survival (OS) | 20.4 Months |
Secondary
Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 23 months
Population: The analysis population included all allocated participants in Part 1 who received study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE | 1 Participants |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE | 3 Participants |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE | 3 Participants |
Secondary
Part 1: Number of Participants Who Experienced One or More AEs
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Population: The analysis population included all allocated participants in Part 1 who received study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | Part 1: Number of Participants Who Experienced One or More AEs | 19 Participants |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Part 1: Number of Participants Who Experienced One or More AEs | 14 Participants |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Part 1: Number of Participants Who Experienced One or More AEs | 17 Participants |
Secondary
Part 2: ORR Per RECIST 1.1 as Assessed by Investigator
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 2 were analyzed for this outcome measure.
Time frame: Up to approximately 29 months
Population: The analysis population consisted of all allocated participants in Part 2 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention. Cohorts D and E in Part 2 did not enroll any participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases | Part 2: ORR Per RECIST 1.1 as Assessed by Investigator | 16.7 Percentage of Participants |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases | Part 2: ORR Per RECIST 1.1 as Assessed by Investigator | 0.0 Percentage of Participants |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases | Part 2: ORR Per RECIST 1.1 as Assessed by Investigator | 0.0 Percentage of Participants |
Secondary
PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
PFS was defined as the time from first dose of study treatment to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurs first as assessed by investigator. Per iRECIST, iCPD was defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Population: The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator | 3.3 Months |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator | 8.2 Months |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator | 20.4 Months |
Secondary
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by investigator. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Time frame: Up to approximately 30 months
Population: The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention. Cohorts D and E in Part 2 did not enroll any participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator | 2.1 Months |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator | 3.3 Months |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator | 15.4 Months |