Cutaneous or Subcutaneous Lymph Node, Hepatocellular Carcinoma, Liver Metastases, Liver Tumors
Conditions
Keywords
Liver tumours
Brief summary
This is a phase 1b/2, multicenter, open-label, basket trial to evaluate the safety of talimogene laherparepvec injected intrahepatically into liver tumors alone and in combination with systemic intravenous (IV) administration of pembrolizumab, in subjects with non-hepatocellular carcinoma (HCC) liver metastases from breast adenocarcinoma (BC), colorectal adenocarcinoma (CRC), gastroesophageal cancer (GEC), melanoma, non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (RCC) in Part 1 Group A, and subjects with HCC with and without viral hepatitis in Part 1 Group B (viral hepatitis is only applicable in combination setting), and to evaluate the efficacy and safety of intratumoral talimogene laherparepvec in combination with systemic pembrolizumab in subjects with advanced triple negative breast cancer (TNBC), hormone receptor positive breast cancer, CRC, cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC) in Part 2 Group A and subjects with HCC with and without viral hepatitis in Part 2 Group B. The objective of Part 1 is to evaluate the safety of intrahepatic injection of talimogene laherparepvec into liver tumors alone and in combination with systemically administered pembrolizumab for the non-HCC (Group A) and HCC (Group B) cohorts separately. Part 2 consists of 2-stage design to evaluate the efficacy and safety of talimogene laherparepvec in combination with systemic pembrolizumab. Efficacy and safety will be evaluated in each of the five non-HCC tumor types from Group A separately. Similarly, the efficacy and safety of the combination treatment will be determined for Group B HCC subjects. As of Protocol Amendment 6 (dated 26 October 2021), intrahepatic injections of talimogene laherparepvec and liver biopsies are no longer performed in this study. Enrollment for this study has stopped.
Interventions
DRUGTalimogene Laherparepvec
Talimogene laherparepvec (T-VEC) administered by intralesional injection into liver tumors, with ultrasound/computed tomography (US/CT) guidance. Part 1: initial dose of T-VEC is 10\^6 plaque forming unit (PFU)/mL up to 4mL in Cohorts 1 & 2, up to 8mL in Cohorts 3 & 4 of the Group A & Group B. The 1st cycle of T-VEC will be 21 (+3) days (from the 1st dose at 10\^6 PFU/mL to the 2nd dose at 10\^7 or 10\^8 PFU/mL). Subsequent cycles of T-VEC will be 21 (±3) days. Max. volume of T-VEC administered at any dose is 4mL (Cohorts 1, 2, 5, and 6) or 8mL (Cohorts 3 & 4) for any individual lesion or for all lesions combined. Part 2: Initial dose of T-VEC is 10\^6 PFU/mL followed by subsequent T-VEC doses at a concentration of 10\^8 PFU/mL. T-VEC volume is up to 8mL based on the size of the inejected lesions. NOTE: as of Protocol Amendment 6 \[dated 26 October 2021\], intrahepatic injections of talimogene laherparepvec and liver biopsies are no longer performed in this study.
DRUGPembrolizumab
Pembrolizumab is a non-Amgen Investigational product that is manufactured by Merck. Pembrolizumab will be labeled, packaged, and distributed by Amgen (or designee) using Amgen (or designee) clinical study drug distribution procedures. Pembrolizumab is supplied as pembrolizumab 100 mg/4 mL vials (25 mg/mL) solution for IV infusion. The trial treatment will consist of a total dose of 200mg administered intravenously every 3 weeks (day 1 of each cycle) for up to 35 cycles.
Sponsors
Merck Sharp & Dohme LLC
Amgen
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
Summary of Subject Eligibility Criteria: Key Inclusion Criteria: Subjects must be age ≥ 18 years at the time of informed consent. Subjects must have histologically or cytologically confirmed disease. Part 1 is restricted to BC, CRC, GEC, melanoma, NSCLC, or RCC with liver metastases or HCC. Part 2 Group A is restricted to advanced hormone receptor positive BC, CRC, TNBC, CSCC, and BCC with or without liver metastases. * Part 2 Hormone receptor positive Breast Cancer Arm only: Histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER) positive and/or progesterone receptor (PrR) positive breast cancer. * Triple negative breast cancer: Histologically and/or cytologically confirmed diagnosis of ER negative, PrR negative, human epidermal growth factor receptor 2 (HER2)-Neu negative. Part 2 Group B is restricted to HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible). For HCC subjects with a diagnosis of hepatitis B, they must be on antiviral therapy for at least 4 weeks prior to enrollment and hepatitis B virus (HBV) viral load by real-time polymerase chain reaction (qPCR) must be \< 100 IU/mL. HCC subjects with past or ongoing hepatitis C infection must have completed treatment for hepatitis C at least 1 month prior to study enrollment and hepatitis C viral load must be undetectable; subjects with hepatitis B and C must fulfill the eligibility criteria for hepatitis B and hepatitis C. Subjects with unresectable locally recurrent TNBC are eligible. Non-HCC subjects must have received at least 1 prior standard of care systemic anti-cancer therapy for their locally advanced or metastatic disease. For the combination cohorts (Cohorts 5 and 6 in Part 1) and Part 2, subjects with melanoma CSCC or NSCLC do not need to have received prior therapy. In Part 1, subjects must have measurable liver tumors and liver tumors that are suitable for injection. In Part 2, subjects must have measurable disease and cutaneous, subcutaneous, lymph node, or liver tumors suitable for injection. NOTE: as of Protocol Amendment 6 \[dated 26 October 2021\], intrahepatic injections of talimogene laherparepvec and liver biopsies are no longer performed in this study, enrollment for this study has stopped. Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1, and life expectancy should be approximately 5 months or more. Adequate hematological, renal, hepatic, and coagulation function is required. Liver function tests may be mildly abnormal but within the parameters. Child-Pugh score must be A. Key
Exclusion criteria
Subjects must not be candidates for surgery or locoregional therapy with curative intent or planned systemic anti-cancer therapy, with the exception of immunotherapy in the combination cohorts (Cohorts 5 and 6 in Part 1 and all subjects in Part 2). Liver tumors must not be estimated to invade approximately more than one-third of the liver. Liver tumor-directed therapy, hepatic surgery or major surgery, antibody-based therapy, or immunotherapy must not have been performed \< 28 days, chemotherapy \< 21 days, and targeted small molecule therapy or hormonal therapy \< 14 days prior to enrollment. Subjects must either (1) have no central nervous system (CNS) metastasis, or carcinomatous meningitis, or (2) if CNS metastasis is present, must have stable treated cerebral metastases. Subjects must not have symptomatic auto-immune disease or be symptomatically immunosuppressed. They must not have a history of solid organ transplantation. For non-HCC, there must not be acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. For HCC with prior hepatitis B and/or C infection, HBV and/or HCV viral load by qPCR must be undetectable, and they must not have had recent treatment within 12 weeks for HBV or HCV with certain antiviral medications in Part 1 Group B cohorts 1-5 and 6a, and Part 2 Group B HCC without viral hepatitis. For all patients in Part 1 and for patients in Part 2 where intrahepatic liver injection is planned (NOTE: as of Protocol Amendment 6 \[dated 26 October 2021\], intrahepatic injections of talimogene laherparepvec and liver biopsies are no longer performed in this study, enrollment for this study has stopped), there should be no macroscopic intravascular invasion of tumors into the main portal vein, hepatic vein, or vena cava. Subjects must not: have active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis); require treatment with an antiherpetic drug; have received live-virus vaccination within 30 days of planned treatment start; have previous therapy with talimogene laherparepvec, oncolytic viruses, or tumor vaccine. Subjects in the combination treatment cohort must not have: a history or evidence of psychiatric, substance abuse, or any other clinically significant disorder; toxic effects of the most recent prior chemotherapy not resolved to grade 1 or less (except alopecia); or expected other cancer therapy while on study with the exception of local radiation to the site of bone or other metastasis for palliative treatment. Male subjects of reproductive potential in the combination treatment must be willing to use acceptable methods of effective contraception during treatment and through 4 months after the last dose of pembrolizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | Cycle 1 and Cycle 2: Day 1 to Day 21 | All toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: * Grade 1: Mild * Grade 2: Moderate * Grade 3: Severe or medically significant but not immediately life threatening * Grade 4: Life threatening consequences * Grade 5: Death related to adverse event (AE) The occurrence of specific pre-defined toxicities during the DLT evaluation period were considered a DLT if judged by the investigator to be related to talimogene laherparepvec and/or pembrolizumab. All Grade 5 toxicities, intolerable toxicities that lead to permanent discontinuation of talimogene laherparepvec and/or pembrolizumab and Grade 3 or higher AEs related to talimogene laherparepvec and/or pembrolizumab that resulted in a study treatment delay by \> 2 weeks were considered DLTs. |
| Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). | Up to 154 weeks | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) per modified irRC-RECIST. * CR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. |
| Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 to 30 days post-last dose of talimogene laherparepvec or pembrolizumab, whichever is later. The maximum duration of talimogene laherparepvec treatment was 102.4 weeks and pembrolizumab treatment was 109.3 weeks in Part 2. | A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. A treatment-related TEAE was defined as a TEAE that was suspected to be related to the study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | Week 1 to Week 7 | The percentage of participants with detectable virus were evaluated from swabs of the exterior of the occlusive dressings. Detectable virus was defined as a positive result by TCID50. |
| Best Overall Response (BOR) Per Modified irRC-RECIST | Up to 297 weeks | BOR was defined as the number of participants with a best visit response in the following order: CR, PR, stable disease (SD), progressive disease (PD), or unevaluable (UE) as per modified irRC-RECIST. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. * SD: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. * PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD. * UE: Any lesion present at baseline which was not assessed or was unable to be evaluated. |
| Durable Response Rate (DRR) Per Modified irRC-RECIST | Up to 297 weeks | DRR per modified irRC-RECIST was defined as the percentage of participants with an objective response (CR/PR) with a duration of response of at least 6 months. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. |
| Duration of Response (DOR) Per Modified irRC-RECIST | Up to 297 weeks | DOR per modified irRC-RECIST was defined as the time from the date of an initial response (CR/PR) that was subsequently confirmed to the earlier of PD or death. DOR was estimated using the Kaplan-Meier method. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. * PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD. |
| Disease Control Rate (DCR) Per Modified irRC-RECIST | Up to 297 weeks | DCR per modified irRC-RECIST was defined as percentage of participants that had a BOR in 1 of the following: CR, PR or SD. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. * SD: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. |
| Progression Free Survival (PFS) Per Modified irRC-RECIST | Up to 297 weeks | PFS was defined as the time from first dose to the date of first of PD per modified irRC-RECIST criteria, or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Participants that did not have an event of death or disease progression were censored at the latter of their last evaluable tumor assessment date or first dose date. * PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD. |
| Overall Survival (OS) | Up to 297 weeks | OS was defined as the time from the date of first dose date to the date of death from any cause. OS time was censored at the last date the participant was known to be alive when the confirmation of death was absent or unknown, or at the date 24 months after the last participant enrolled if the last known to be alive/death date was beyond it. One month = 365.25/12 days. OS was estimated using the Kaplan-Meier method. |
| Part 1 Only: Number of Participants Who Experienced a TEAE | Day 1 to 30 days post-last dose of talimogene laherparepvec or pembrolizumab, whichever is later. The maximum duration of talimogene laherparepvec treatment was 34.1 weeks and pembrolizumab treatment was 98.3 weeks in Part 1. | A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. A treatment-related TEAE was defined as a TEAE that was suspected to be related to the study treatment. |
| Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | Week 1 to Week 10 | The percentage of participants with detectable virus were evaluated from swabs of skin surface of injections. Detectable virus was defined as a positive result by TCID50. |
| Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | Week 1 to Week 10 | Urine samples were tested using qPCR. Detectable DNA was defined as a positive result by qPCR analysis. |
| Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycles 2, 3 and 4: Day 1 pre-dose. Each cycle was 21 days. | Blood samples were tested using qPCR. A participant was defined as having cleared talimogene laherparepvec if a negative qPCR in a sample was obtained following a prior positive test and if there were no subsequent positive test results in the same cycle. |
| Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycles 2, 3 and 4: Day 1 pre-dose. Each cycle was 21 days. | Urine samples were tested using qPCR. A participant was defined as having cleared talimogene laherparepvec if a negative qPCR in a sample was obtained following a prior positive test and if there were no subsequent positive test results in the same cycle. |
| Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | Week 1 to Week 10 | The number of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of skin surface of injections. Detectable DNA was defined as a positive result by qPCR analysis. |
| Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | Part 1: Week 1 to Week 37. Part 2: Week 1 to Week 43 | The percentage of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of the oral mucosa. Detectable DNA was defined as a positive result by qPCR analysis. |
| Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa | Week 1 to Week 7 | The percentage of participants with detectable virus were evaluated from swabs of the oral mucosa. Detectable virus was defined as a positive result by TCID50. |
| Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Lesions Suspected to be Herpetic in Origin | Day 1 to 30 days post-last dose of talimogene laherparepvec. The maximum duration of talimogene laherparepvec treatment was 102.4 weeks and pembrolizumab treatment was 109.3 weeks. | The percentage of participants with positive qPCR were evaluated in any swab of a lesion suspected to be herpetic in origin. Detectable DNA was defined as a positive result by qPCR analysis. Participants returned to the clinic within 3 days of the occurrence of reportable lesion suspected to be herpetic in origin such as cold sores or vesicles. The lesion was evaluated by the Investigator and swabbed if herpes simplex virus infection was suspected. |
| Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | Week 1 to Week 10 | Blood samples were tested using real-time polymerase chain reaction (qPCR). Detectable DNA was defined as a positive result by qPCR analysis. |
| Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | Week 1 to Week 7 | The percentage of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of the exterior of the occlusive dressing. Detectable DNA was defined as a positive result by qPCR analysis. |
| Part 1 Only: ORR Per Modified irRC-RECIST | Up to 297 weeks | ORR was defined as the percentage of participants with a best overall response of CR or PR per modified irRC-RECIST. * CR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. |
Countries
Australia, Austria, Belgium, Germany, Poland, South Korea, Spain, Switzerland, United States
Participant flow
Recruitment details
127 participants were enrolled at 22 centers in Australia, Europe, South Korea and the United States from February 2016 to July 2023. As of protocol amendment 6 (dated 26 October 2021), intrahepatic injections of talimogene laherparepvec were no longer performed.
Pre-assignment details
Of the 190 participants screened, 127 participants were enrolled and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Monotherapy Group A Participants with non-hepatocellular carcinoma (non-HCC) were administered talimogene laherparepvec by intralesional injection at an initial concentration of 10\^6 plaque forming unit (PFU)/mL in a volume of up to 4mL in Cohorts 1 & 2 and up to a volume of 8 mL in Cohorts 3 & 4 on Day 1 of the first 21-day cycle. The concentration of talimogene laherparepvec doses in the second and subsequent 21-day cycles were 10\^7 (Cohorts 1 & 4) or 10\^8 PFU/mL (Cohorts 2 & 3). | 23 |
| Part 1: Monotherapy Group B Participants with hepatocellular carcinoma (HCC) were administered talimogene laherparepvec by intralesional injection at an initial concentration of 10\^6 plaque forming unit (PFU)/mL in a volume of up to 4mL in Cohorts 1 & 2 and up to a volume of 8 mL in Cohorts 3 & 4 on Day 1 of the first 21-day cycle. The concentration of talimogene laherparepvec doses in the second and subsequent 21-day cycles were 10\^7 (Cohorts 1 & 4) or 10\^8 PFU/mL (Cohorts 2 & 3). | 5 |
| Part 1: Combination Therapy Group A Participants with non-hepatocellular carcinoma (non-HCC) were administered talimogene laherparepvec by intralesional injection at an initial concentration of 10\^6 plaque forming unit (PFU)/mL in a volume of up to 4mL in Cohorts 5 & 6 on Day 1 of the first 21-day cycle. The concentration of talimogene laherparepvec doses in the second and subsequent 21-day cycles were 10\^7 (Cohort 5) or 10\^8 PFU/mL (Cohorts 6).
Participants were also administered 200 mg of pembrolizumab on Day 1 of each 21-day cycle as an intravenous infusion. | 24 |
| Part 1: Combination Therapy Group B Participants with hepatocellular carcinoma (HCC) were administered talimogene laherparepvec by intralesional injection at an initial concentration of 10\^6 plaque forming unit (PFU)/mL in a volume of up to 4mL in Cohorts 5, 6a (participants without viral hepatitis) and 6b (participants with well controlled viral hepatitis) on Day 1 of the first 21-day cycle. The concentration of talimogene laherparepvec doses in the second and subsequent 21-day cycles were 10\^7 (Cohort 5) or 10\^8 PFU/mL (Cohorts 6a and 6b).
Participants were also administered 200 mg of pembrolizumab on Day 1 of each 21-day cycle as an intravenous infusion. | 22 |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) Participants with HRBC were administered talimogene laherparepvec by intralesional injection at the maximum tolerated concentration (MTC) and maximum tolerated volume (MTV) identified in Part 1 on Day 1 of each 21-day cycle.
Participants were also administered 200 mg of pembrolizumab on Day 1 of each 21-day cycle as an intravenous infusion. | 10 |
| Part 2: Triple Negative Breast Cancer (TNBC) Participants with TNBC were administered talimogene laherparepvec by intralesional injection at the MTC and MTV identified in Part 1 on Day 1 of each 21-day cycle.
Participants were also administered 200 mg of pembrolizumab on Day 1 of each 21-day cycle as an intravenous infusion. | 18 |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) Participants with CSCC were administered talimogene laherparepvec by intralesional injection at the MTC and MTV identified in Part 1 on Day 1 of each 21-day cycle.
Participants were also administered 200 mg of pembrolizumab on Day 1 of each 21-day cycle as an intravenous infusion. | 10 |
| Part 2: Basal Cell Carcinoma (BCC) Participants with BCC were administered talimogene laherparepvec by intralesional injection at the MTC and MTV identified in Part 1 on Day 1 of each 21-day cycle.
Participants were also administered 200 mg of pembrolizumab on Day 1 of each 21-day cycle as an intravenous infusion. | 5 |
| Part 2: Colorectal Adenocarcinoma (CRC) Participants with CRC were administered talimogene laherparepvec by intralesional injection at the MTC and MTV identified in Part 1 on Day 1 of each 21-day cycle.
Participants were also administered 200 mg of pembrolizumab on Day 1 of each 21-day cycle as an intravenous infusion. | 10 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 21 | 3 | 22 | 14 | 8 | 12 | 5 | 4 | 8 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 4 | 1 | 3 | 4 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Monotherapy Group B | Part 1: Combination Therapy Group A | Part 1: Combination Therapy Group B | Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Part 2: Triple Negative Breast Cancer (TNBC) | Part 1: Monotherapy Group A | Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Part 2: Basal Cell Carcinoma (BCC) | Part 2: Colorectal Adenocarcinoma (CRC) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 - 64 years | 3 Participants | 17 Participants | 10 Participants | 8 Participants | 15 Participants | 16 Participants | 5 Participants | 4 Participants | 6 Participants | 84 Participants |
| Age, Customized 65 - 74 years | 2 Participants | 5 Participants | 8 Participants | 2 Participants | 2 Participants | 7 Participants | 2 Participants | 1 Participants | 4 Participants | 33 Participants |
| Age, Customized 75 - 84 years | 0 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 10 Participants |
| Age, Customized >= 85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 23 Participants | 21 Participants | 10 Participants | 16 Participants | 21 Participants | 9 Participants | 4 Participants | 10 Participants | 119 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 | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 8 Participants | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 19 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 23 Participants | 14 Participants | 10 Participants | 15 Participants | 20 Participants | 7 Participants | 4 Participants | 9 Participants | 106 Participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 5 Participants | 10 Participants | 18 Participants | 11 Participants | 3 Participants | 2 Participants | 4 Participants | 65 Participants |
| Sex: Female, Male Male | 3 Participants | 14 Participants | 17 Participants | 0 Participants | 0 Participants | 12 Participants | 7 Participants | 3 Participants | 6 Participants | 62 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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 21 / 23 | 3 / 5 | 22 / 24 | 14 / 22 | 8 / 10 | 13 / 18 | 5 / 10 | 4 / 5 | 8 / 10 |
| other Total, other adverse events | 23 / 23 | 5 / 5 | 24 / 24 | 21 / 22 | 10 / 10 | 15 / 18 | 8 / 10 | 5 / 5 | 10 / 10 |
| serious Total, serious adverse events | 10 / 23 | 2 / 5 | 10 / 24 | 11 / 22 | 4 / 10 | 7 / 18 | 5 / 10 | 3 / 5 | 3 / 10 |
Outcome results
Primary
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
All toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: * Grade 1: Mild * Grade 2: Moderate * Grade 3: Severe or medically significant but not immediately life threatening * Grade 4: Life threatening consequences * Grade 5: Death related to adverse event (AE) The occurrence of specific pre-defined toxicities during the DLT evaluation period were considered a DLT if judged by the investigator to be related to talimogene laherparepvec and/or pembrolizumab. All Grade 5 toxicities, intolerable toxicities that lead to permanent discontinuation of talimogene laherparepvec and/or pembrolizumab and Grade 3 or higher AEs related to talimogene laherparepvec and/or pembrolizumab that resulted in a study treatment delay by \> 2 weeks were considered DLTs.
Time frame: Cycle 1 and Cycle 2: Day 1 to Day 21
Population: DLT Analysis Set: Participants who had at least 1 dose of planned monotherapy or combination treatment and had the opportunity to be on treatment for at least 6 weeks from the initial dosing of study treatment \& received at least 1 additional dose of monotherapy or combination or experienced a DLT during the DLT-evaluation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Monotherapy Group A | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 2 Participants |
| Part 1: Monotherapy Group B | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1: Combination Therapy Group A | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 1 Participants |
| Part 1: Combination Therapy Group B | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 1 Participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 2: Basal Cell Carcinoma (BCC) | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
Primary
Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. A treatment-related TEAE was defined as a TEAE that was suspected to be related to the study treatment.
Time frame: Day 1 to 30 days post-last dose of talimogene laherparepvec or pembrolizumab, whichever is later. The maximum duration of talimogene laherparepvec treatment was 102.4 weeks and pembrolizumab treatment was 109.3 weeks in Part 2.
Population: Safety Analysis Set (Part 2): Included all participants in Part 2 who have received at least 1 dose of talimogene laherparepvec or at least 1 dose of pembrolizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Monotherapy Group A | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Treatment-related TEAEs | 10 Participants |
| Part 1: Monotherapy Group A | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | TEAEs | 10 Participants |
| Part 1: Monotherapy Group B | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Treatment-related TEAEs | 12 Participants |
| Part 1: Monotherapy Group B | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | TEAEs | 17 Participants |
| Part 1: Combination Therapy Group A | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | TEAEs | 9 Participants |
| Part 1: Combination Therapy Group A | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Treatment-related TEAEs | 4 Participants |
| Part 1: Combination Therapy Group B | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | TEAEs | 5 Participants |
| Part 1: Combination Therapy Group B | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Treatment-related TEAEs | 5 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | TEAEs | 10 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Treatment-related TEAEs | 10 Participants |
Primary
Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST).
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) per modified irRC-RECIST. * CR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.
Time frame: Up to 154 weeks
Population: Full Analysis Set (Part 2): Included all participants in Part 2 who received at least 1 dose of talimogene laherparepvec and at least 1 dose of pembrolizumab in combination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). | 10.0 percentage of participants |
| Part 1: Monotherapy Group B | Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). | 16.7 percentage of participants |
| Part 1: Combination Therapy Group A | Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). | 10.0 percentage of participants |
| Part 1: Combination Therapy Group B | Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). | 20.0 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). | 0.0 percentage of participants |
Secondary
Best Overall Response (BOR) Per Modified irRC-RECIST
BOR was defined as the number of participants with a best visit response in the following order: CR, PR, stable disease (SD), progressive disease (PD), or unevaluable (UE) as per modified irRC-RECIST. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. * SD: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. * PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD. * UE: Any lesion present at baseline which was not assessed or was unable to be evaluated.
Time frame: Up to 297 weeks
Population: Full Analysis Set: Included all participants who received at least 1 dose of talimogene laherparepvec in monotherapy and combination cohorts and at least 1 dose of pembrolizumab in combination cohorts in Part 1 and Part 2.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Monotherapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 1: Monotherapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 2 Participants |
| Part 1: Monotherapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 7 Participants |
| Part 1: Monotherapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 0 Participants |
| Part 1: Monotherapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 13 Participants |
| Part 1: Monotherapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 1 Participants |
| Part 1: Monotherapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 0 Participants |
| Part 1: Monotherapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 1: Monotherapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 0 Participants |
| Part 1: Monotherapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 1 Participants |
| Part 1: Monotherapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 1 Participants |
| Part 1: Monotherapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 3 Participants |
| Part 1: Combination Therapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 7 Participants |
| Part 1: Combination Therapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 4 Participants |
| Part 1: Combination Therapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 1 Participants |
| Part 1: Combination Therapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 1: Combination Therapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 10 Participants |
| Part 1: Combination Therapy Group A | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 2 Participants |
| Part 1: Combination Therapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 1: Combination Therapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 0 Participants |
| Part 1: Combination Therapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 6 Participants |
| Part 1: Combination Therapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 3 Participants |
| Part 1: Combination Therapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 3 Participants |
| Part 1: Combination Therapy Group B | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 10 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 5 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 1 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 3 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 0 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 1 Participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 6 Participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 2 Participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 5 Participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 1 Participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 1 Participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 3 Participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 2 Participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 4 Participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 1 Participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 1 Participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 2 Participants |
| Part 2: Basal Cell Carcinoma (BCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 2 Participants |
| Part 2: Basal Cell Carcinoma (BCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 1 Participants |
| Part 2: Basal Cell Carcinoma (BCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 2: Basal Cell Carcinoma (BCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 2 Participants |
| Part 2: Basal Cell Carcinoma (BCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 0 Participants |
| Part 2: Basal Cell Carcinoma (BCC) | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 0 Participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PR | 0 Participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Best Overall Response (BOR) Per Modified irRC-RECIST | PD | 1 Participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Best Overall Response (BOR) Per Modified irRC-RECIST | CR | 0 Participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Best Overall Response (BOR) Per Modified irRC-RECIST | SD | 3 Participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Best Overall Response (BOR) Per Modified irRC-RECIST | UE | 5 Participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Best Overall Response (BOR) Per Modified irRC-RECIST | Not Done | 1 Participants |
Secondary
Disease Control Rate (DCR) Per Modified irRC-RECIST
DCR per modified irRC-RECIST was defined as percentage of participants that had a BOR in 1 of the following: CR, PR or SD. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. * SD: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
Time frame: Up to 297 weeks
Population: Full Analysis Set: Included all participants who received at least 1 dose of talimogene laherparepvec in monotherapy and combination cohorts and at least 1 dose of pembrolizumab in combination cohorts in Part 1 and Part 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Disease Control Rate (DCR) Per Modified irRC-RECIST | 4.3 percentage of participants |
| Part 1: Monotherapy Group B | Disease Control Rate (DCR) Per Modified irRC-RECIST | 20.0 percentage of participants |
| Part 1: Combination Therapy Group A | Disease Control Rate (DCR) Per Modified irRC-RECIST | 25.0 percentage of participants |
| Part 1: Combination Therapy Group B | Disease Control Rate (DCR) Per Modified irRC-RECIST | 40.9 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Disease Control Rate (DCR) Per Modified irRC-RECIST | 20.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Disease Control Rate (DCR) Per Modified irRC-RECIST | 22.2 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Disease Control Rate (DCR) Per Modified irRC-RECIST | 20.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Disease Control Rate (DCR) Per Modified irRC-RECIST | 60.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Disease Control Rate (DCR) Per Modified irRC-RECIST | 30.0 percentage of participants |
Secondary
Durable Response Rate (DRR) Per Modified irRC-RECIST
DRR per modified irRC-RECIST was defined as the percentage of participants with an objective response (CR/PR) with a duration of response of at least 6 months. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.
Time frame: Up to 297 weeks
Population: Full Analysis Set: Included all participants who received at least 1 dose of talimogene laherparepvec in monotherapy and combination cohorts and at least 1 dose of pembrolizumab in combination cohorts in Part 1 and Part 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Durable Response Rate (DRR) Per Modified irRC-RECIST | 0.0 percentage of participants |
| Part 1: Monotherapy Group B | Durable Response Rate (DRR) Per Modified irRC-RECIST | 0.0 percentage of participants |
| Part 1: Combination Therapy Group A | Durable Response Rate (DRR) Per Modified irRC-RECIST | 8.3 percentage of participants |
| Part 1: Combination Therapy Group B | Durable Response Rate (DRR) Per Modified irRC-RECIST | 9.1 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Durable Response Rate (DRR) Per Modified irRC-RECIST | 10.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Durable Response Rate (DRR) Per Modified irRC-RECIST | 11.1 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Durable Response Rate (DRR) Per Modified irRC-RECIST | 10.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Durable Response Rate (DRR) Per Modified irRC-RECIST | 20.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Durable Response Rate (DRR) Per Modified irRC-RECIST | 0.0 percentage of participants |
Secondary
Duration of Response (DOR) Per Modified irRC-RECIST
DOR per modified irRC-RECIST was defined as the time from the date of an initial response (CR/PR) that was subsequently confirmed to the earlier of PD or death. DOR was estimated using the Kaplan-Meier method. * CR: Disappearance of all lesions and confirmation by assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation. * PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD.
Time frame: Up to 297 weeks
Population: Full Analysis Set: Included all participants who received at least 1 dose of talimogene laherparepvec in monotherapy and combination cohorts and at least 1 dose of pembrolizumab in combination cohorts in Part 1 and Part 2. Only participants who had a BOR of CR/PR were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Combination Therapy Group A | Duration of Response (DOR) Per Modified irRC-RECIST | 16.8 months |
| Part 1: Combination Therapy Group B | Duration of Response (DOR) Per Modified irRC-RECIST | 8.9 months |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Duration of Response (DOR) Per Modified irRC-RECIST | NA months |
| Part 2: Triple Negative Breast Cancer (TNBC) | Duration of Response (DOR) Per Modified irRC-RECIST | 23.1 months |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Duration of Response (DOR) Per Modified irRC-RECIST | NA months |
| Part 2: Basal Cell Carcinoma (BCC) | Duration of Response (DOR) Per Modified irRC-RECIST | NA months |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of first dose date to the date of death from any cause. OS time was censored at the last date the participant was known to be alive when the confirmation of death was absent or unknown, or at the date 24 months after the last participant enrolled if the last known to be alive/death date was beyond it. One month = 365.25/12 days. OS was estimated using the Kaplan-Meier method.
Time frame: Up to 297 weeks
Population: Full Analysis Set: Included all participants who received at least 1 dose of talimogene laherparepvec in monotherapy and combination cohorts and at least 1 dose of pembrolizumab in combination cohorts in Part 1 and Part 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Monotherapy Group A | Overall Survival (OS) | 8.7 months |
| Part 1: Monotherapy Group B | Overall Survival (OS) | 9.1 months |
| Part 1: Combination Therapy Group A | Overall Survival (OS) | 7.8 months |
| Part 1: Combination Therapy Group B | Overall Survival (OS) | 12.8 months |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Overall Survival (OS) | 9.1 months |
| Part 2: Triple Negative Breast Cancer (TNBC) | Overall Survival (OS) | 10.2 months |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Overall Survival (OS) | 9.6 months |
| Part 2: Basal Cell Carcinoma (BCC) | Overall Survival (OS) | 16.4 months |
| Part 2: Colorectal Adenocarcinoma (CRC) | Overall Survival (OS) | 11.2 months |
Secondary
Part 1 Only: Number of Participants Who Experienced a TEAE
A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. A treatment-related TEAE was defined as a TEAE that was suspected to be related to the study treatment.
Time frame: Day 1 to 30 days post-last dose of talimogene laherparepvec or pembrolizumab, whichever is later. The maximum duration of talimogene laherparepvec treatment was 34.1 weeks and pembrolizumab treatment was 98.3 weeks in Part 1.
Population: Safety Analysis Set (Part 1): Included all participants in Part 1 who have received at least 1 dose of talimogene laherparepvec or at least 1 dose of pembrolizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Monotherapy Group A | Part 1 Only: Number of Participants Who Experienced a TEAE | TEAEs | 23 Participants |
| Part 1: Monotherapy Group A | Part 1 Only: Number of Participants Who Experienced a TEAE | Treatment-related TEAEs | 23 Participants |
| Part 1: Monotherapy Group B | Part 1 Only: Number of Participants Who Experienced a TEAE | Treatment-related TEAEs | 5 Participants |
| Part 1: Monotherapy Group B | Part 1 Only: Number of Participants Who Experienced a TEAE | TEAEs | 5 Participants |
| Part 1: Combination Therapy Group A | Part 1 Only: Number of Participants Who Experienced a TEAE | Treatment-related TEAEs | 22 Participants |
| Part 1: Combination Therapy Group A | Part 1 Only: Number of Participants Who Experienced a TEAE | TEAEs | 24 Participants |
| Part 1: Combination Therapy Group B | Part 1 Only: Number of Participants Who Experienced a TEAE | TEAEs | 21 Participants |
| Part 1: Combination Therapy Group B | Part 1 Only: Number of Participants Who Experienced a TEAE | Treatment-related TEAEs | 20 Participants |
Secondary
Part 1 Only: ORR Per Modified irRC-RECIST
ORR was defined as the percentage of participants with a best overall response of CR or PR per modified irRC-RECIST. * CR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. * PR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks (28 days) after first documentation.
Time frame: Up to 297 weeks
Population: Full Analysis Set (Part 1): Included all participants in Part 1 who received at least 1 dose of talimogene laherparepvec in monotherapy and combination cohorts and at least 1 dose of pembrolizumab in combination cohorts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Part 1 Only: ORR Per Modified irRC-RECIST | 0.0 percentage of participants |
| Part 1: Monotherapy Group B | Part 1 Only: ORR Per Modified irRC-RECIST | 0.0 percentage of participants |
| Part 1: Combination Therapy Group A | Part 1 Only: ORR Per Modified irRC-RECIST | 8.3 percentage of participants |
| Part 1: Combination Therapy Group B | Part 1 Only: ORR Per Modified irRC-RECIST | 13.6 percentage of participants |
Secondary
Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood
Blood samples were tested using qPCR. A participant was defined as having cleared talimogene laherparepvec if a negative qPCR in a sample was obtained following a prior positive test and if there were no subsequent positive test results in the same cycle.
Time frame: Cycles 2, 3 and 4: Day 1 pre-dose. Each cycle was 21 days.
Population: Blood Clearance Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least 2 post dose samples, collected within the same dosing cycle. Participants must have had at least 1 positive sample and at least 1 subsequent sample at any time during the cycle. All participants included in the overall number of participants contributed analyzed data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 4, Day 1 Pre-dose | 66.7 percentage of participants |
| Part 1: Monotherapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 66.7 percentage of participants |
| Part 1: Monotherapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 73.9 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 70.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 52.2 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 4, Day 1 Pre-dose | 37.5 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 95.2 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 77.8 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 85.7 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 75.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 80.0 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 66.7 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 75.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 66.7 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 4, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 2, Day 1 Pre-dose | 60.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood | Cycle 3, Day 1 Pre-dose | 70.0 percentage of participants |
Secondary
Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine
Urine samples were tested using qPCR. A participant was defined as having cleared talimogene laherparepvec if a negative qPCR in a sample was obtained following a prior positive test and if there were no subsequent positive test results in the same cycle.
Time frame: Cycles 2, 3 and 4: Day 1 pre-dose. Each cycle was 21 days.
Population: Urine Clearance Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least 2 post dose samples, collected within the same dosing cycle. Participants must have had at least 1 positive sample and at least 1 subsequent sample at any time during the cycle. All participants included in the overall number of participants contributed analyzed data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 2, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Monotherapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 2, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 2, Day 1 Pre-dose | 80.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 2, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 2, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 2, Day 1 Pre-dose | 0.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 2, Day 1 Pre-dose | 100.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine | Cycle 3, Day 1 Pre-dose | 100.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood
Blood samples were tested using real-time polymerase chain reaction (qPCR). Detectable DNA was defined as a positive result by qPCR analysis.
Time frame: Week 1 to Week 10
Population: Blood Evaluable Analysis Set: Included all participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one post dose blood sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 100.0 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 100.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 100.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 95.5 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 90.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 88.9 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 50.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 60.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood | 100.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing
The percentage of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of the exterior of the occlusive dressing. Detectable DNA was defined as a positive result by qPCR analysis.
Time frame: Week 1 to Week 7
Population: Exterior of Occlusive Dressing Evaluable Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the exterior of the occlusive dressing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 30.4 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 20.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 39.1 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 61.9 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 66.7 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 33.3 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 44.4 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 60.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing | 14.3 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa
The percentage of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of the oral mucosa. Detectable DNA was defined as a positive result by qPCR analysis.
Time frame: Part 1: Week 1 to Week 37. Part 2: Week 1 to Week 43
Population: Oral Mucosa Evaluable Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the oral mucosa.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 0.0 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 0.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 29.2 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 4.5 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 0.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 12.5 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 10.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 60.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa | 10.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site
The number of participants with positive qPCR and subsequent positive plaque assays were evaluated from swabs of skin surface of injections. Detectable DNA was defined as a positive result by qPCR analysis.
Time frame: Week 1 to Week 10
Population: Skin Surface of Injections Evaluable Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the skin surface of injections.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 69.6 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 60.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 79.2 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 72.7 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 60.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 68.8 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 80.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 100.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site | 60.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Lesions Suspected to be Herpetic in Origin
The percentage of participants with positive qPCR were evaluated in any swab of a lesion suspected to be herpetic in origin. Detectable DNA was defined as a positive result by qPCR analysis. Participants returned to the clinic within 3 days of the occurrence of reportable lesion suspected to be herpetic in origin such as cold sores or vesicles. The lesion was evaluated by the Investigator and swabbed if herpes simplex virus infection was suspected.
Time frame: Day 1 to 30 days post-last dose of talimogene laherparepvec. The maximum duration of talimogene laherparepvec treatment was 102.4 weeks and pembrolizumab treatment was 109.3 weeks.
Population: Reactive Swab Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab sample collected from lesions that were suspected to be herpetic in origin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Lesions Suspected to be Herpetic in Origin | 0.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Lesions Suspected to be Herpetic in Origin | 100.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine
Urine samples were tested using qPCR. Detectable DNA was defined as a positive result by qPCR analysis.
Time frame: Week 1 to Week 10
Population: Urine Evaluable Analysis Set: Included all participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one post dose urine sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 34.8 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 40.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 37.5 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 54.5 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 10.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 27.8 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 20.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 0.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine | 30.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing
The percentage of participants with detectable virus were evaluated from swabs of the exterior of the occlusive dressings. Detectable virus was defined as a positive result by TCID50.
Time frame: Week 1 to Week 7
Population: Exterior of Occlusive Dressing Evaluable Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the exterior of the occlusive dressing. Only participants with a positive exterior of occlusive dressing qPCR test were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 16.7 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing | 0.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa
The percentage of participants with detectable virus were evaluated from swabs of the oral mucosa. Detectable virus was defined as a positive result by TCID50.
Time frame: Week 1 to Week 7
Population: Oral Mucosa Evaluable Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the oral mucosa. Only participants with a positive oral mucosa qPCR test were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa | 0.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa | 0.0 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa | 0.0 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa | 0.0 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa | 0.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa | 0.0 percentage of participants |
Secondary
Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site
The percentage of participants with detectable virus were evaluated from swabs of skin surface of injections. Detectable virus was defined as a positive result by TCID50.
Time frame: Week 1 to Week 10
Population: Skin Surface of Injections Evaluable Analysis Set: Included participants who were enrolled, received at least one dose of talimogene laherparepvec, and had at least one swab collected from the skin surface of injections. Only participants with a positive surface of injection site qPCR test were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Monotherapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 0.0 percentage of participants |
| Part 1: Monotherapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 0.0 percentage of participants |
| Part 1: Combination Therapy Group A | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 0.0 percentage of participants |
| Part 1: Combination Therapy Group B | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 0.0 percentage of participants |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 16.7 percentage of participants |
| Part 2: Triple Negative Breast Cancer (TNBC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 0.0 percentage of participants |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 12.5 percentage of participants |
| Part 2: Basal Cell Carcinoma (BCC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 0.0 percentage of participants |
| Part 2: Colorectal Adenocarcinoma (CRC) | Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site | 0.0 percentage of participants |
Secondary
Progression Free Survival (PFS) Per Modified irRC-RECIST
PFS was defined as the time from first dose to the date of first of PD per modified irRC-RECIST criteria, or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Participants that did not have an event of death or disease progression were censored at the latter of their last evaluable tumor assessment date or first dose date. * PD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmation by a repeat, consecutive assessment no less than 4 weeks (28 days) from the date first documented PD.
Time frame: Up to 297 weeks
Population: Full Analysis Set: Included all participants who received at least 1 dose of talimogene laherparepvec in monotherapy and combination cohorts and at least 1 dose of pembrolizumab in combination cohorts in Part 1 and Part 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Monotherapy Group A | Progression Free Survival (PFS) Per Modified irRC-RECIST | 2.3 months |
| Part 1: Monotherapy Group B | Progression Free Survival (PFS) Per Modified irRC-RECIST | 3.9 months |
| Part 1: Combination Therapy Group A | Progression Free Survival (PFS) Per Modified irRC-RECIST | 2.0 months |
| Part 1: Combination Therapy Group B | Progression Free Survival (PFS) Per Modified irRC-RECIST | 8.1 months |
| Part 2: Hormone Receptor Positive Breast Cancer (HRBC) | Progression Free Survival (PFS) Per Modified irRC-RECIST | 6.1 months |
| Part 2: Triple Negative Breast Cancer (TNBC) | Progression Free Survival (PFS) Per Modified irRC-RECIST | 2.9 months |
| Part 2: Cutaneous Squamous Cell Carcinoma (CSCC) | Progression Free Survival (PFS) Per Modified irRC-RECIST | 5.4 months |
| Part 2: Basal Cell Carcinoma (BCC) | Progression Free Survival (PFS) Per Modified irRC-RECIST | 16.4 months |
| Part 2: Colorectal Adenocarcinoma (CRC) | Progression Free Survival (PFS) Per Modified irRC-RECIST | 8.8 months |