Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Tumors Alone and in Combination With Systemic Pembrolizumab MK-3475-611/Keynote-611
Hepatocellular Carcinoma · Liver Metastases · Cutaneous or Subcutaneous Lymph Node · Liver Tumors
Bottom Line
View on ClinicalTrials.gov: NCT02509507 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Talimogene Laherparepvec (Drug); Pembrolizumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) |
2; 0; 1; 0; 1; 0 | — |
| PRIMARY Part 2 Only: Objective Response Rate (ORR) Per Modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST). |
10.0; 16.7; 10.0; 20.0; 0.0 | — |
| PRIMARY Part 2 Only: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) |
10; 17; 9; 5; 10; 10 | — |
| SECONDARY Part 1 Only: ORR Per Modified irRC-RECIST |
0.0; 0.0; 8.3; 13.6 | — |
| SECONDARY Best Overall Response (BOR) Per Modified irRC-RECIST |
0; 0; 0; 0; 0; 2 | — |
| SECONDARY Durable Response Rate (DRR) Per Modified irRC-RECIST |
0.0; 0.0; 8.3; 9.1; 10.0; 11.1 | — |
| SECONDARY Duration of Response (DOR) Per Modified irRC-RECIST |
16.8; 8.9; NA; 23.1; NA; NA | — |
| SECONDARY Disease Control Rate (DCR) Per Modified irRC-RECIST |
4.3; 20.0; 25.0; 40.9; 20.0; 22.2 | — |
| SECONDARY Progression Free Survival (PFS) Per Modified irRC-RECIST |
2.3; 3.9; 2.0; 8.1; 6.1; 2.9 | — |
| SECONDARY Overall Survival (OS) |
8.7; 9.1; 7.8; 12.8; 9.1; 10.2 | — |
| SECONDARY Part 1 Only: Number of Participants Who Experienced a TEAE |
23; 5; 24; 21; 23; 5 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) in Blood |
100.0; 100.0; 100.0; 95.5; 90.0; 88.9 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Urine |
34.8; 40.0; 37.5; 54.5; 10.0; 27.8 | — |
| SECONDARY Percentage of Participants With Clearance of Talimogene Laherparepvec in Blood |
73.9; 100.0; 52.2; 95.2; 85.7; 80.0 | — |
| SECONDARY Percentage of Participants With Clearance of Talimogene Laherparepvec in Urine |
100.0; 100.0; 80.0; 100.0; 100.0; 0.0 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Surface of Injection Site |
69.6; 60.0; 79.2; 72.7; 60.0; 68.8 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Surface of Injection Site |
0.0; 0.0; 0.0; 0.0; 16.7; 0.0 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Exterior of the Occlusive Dressing |
30.4; 20.0; 39.1; 61.9; 66.7; 33.3 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Exterior of the Occlusive Dressing |
0.0; 0.0; 0.0; 0.0; 16.7; 0.0 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec DNA at the Oral Mucosa |
0.0; 0.0; 29.2; 4.5; 0.0; 12.5 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec Virus at the Oral Mucosa |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Detectable Talimogene Laherparepvec DNA in Lesions Suspected to be Herpetic in Origin |
0.0; 100.0 | — |
Summary
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT02509507). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.