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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02509507




Registration number
NCT02509507
Ethics application status
Date submitted
10/07/2015
Date registered
28/07/2015
Date last updated
18/03/2021

Titles & IDs
Public title
Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Tumors Alone and in Combination With Systemic Pembrolizumab MK-3475-611/Keynote-611
Scientific title
A Phase 1b/2, Multicenter, Open-label, Basket Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Liver Tumors Alone and in Combination With Systemic Pembrolizumab in Phase 1b and to Evaluate the Efficacy and Safety of Intratumoral Talimogene Laherparepvec in Combination With Systemic Pembrolizumab to Treat Subjects With Advanced Solid Tumors in Phase 2 (MASTERKEY-318)
Secondary ID [1] 0 0
2014-005386-67
Secondary ID [2] 0 0
20140318
Universal Trial Number (UTN)
Trial acronym
MASTERKEY-318
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 0 0
Liver Metastases 0 0
Cutaneous or Subcutaneous Lymph Node 0 0
Liver Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Liver
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Talimogene Laherparepvec
Treatment: Drugs - Pembrolizumab

Experimental: Phase Ib/II Talimogene Laherparepvec - Talimogene Laherparepvec

Experimental: Phase Ib/II Talimogene Laherparepvec + Pembrolizumab - Combination treatment of Talimogene Laherparepvec and Pembrolizumab


Treatment: Drugs: Talimogene Laherparepvec
Talimogene laherparepvec (T-VEC) administered by intralesional injection into liver tumors, with US/CT guidance. Part 1: initial dose of T-VEC is 10^6 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.

Treatment: Drugs: Pembrolizumab
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Subject incidence DLTs separately in Group A and B observed in monotherapy and combination cohorts and in each tumor type seperately in Part 2
Timepoint [1] 0 0
3 year
Primary outcome [2] 0 0
To evaluate in Part 2 ORR per modified irRC-RECIST separately by tumor type (HR+, TNBC, CRC, BCC, CSCC, HCC)
Timepoint [2] 0 0
2 years
Secondary outcome [1] 0 0
Safety: Subject incidence of treatment-related and treatment-emergent adverse events in monotherapy and combination of Part 1 and each separate tumour type in Part 2
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Safety: To estimate the incidence of detectable talimogene laherparepvec DNA in blood and urine
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Safety: To estimate the incidence of clearance of talimogene laherparepvec DNA from blood and urine
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Safety: To estimate the rate of detection and incidence of talimogene laherparepvec DNA and virus at the surface of talimogene laherparepvec injection site, the exterior of the occlusive dressing, and the oral mucosa
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Safety: To estimate the incidence of talimogene laherparepvec DNA detection in lesions suspected to be herpetic in origin
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Efficacy: Objective response rate (ORR) - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Efficacy: Best overall response (BOR) - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
Efficacy: Durable response rate (DRR) - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
Efficacy: Duration of response (DOR) - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [9] 0 0
5 years
Secondary outcome [10] 0 0
Efficacy: Response in injected and uninjected lesions - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [10] 0 0
5 years
Secondary outcome [11] 0 0
Efficacy: Disease control rate (DCR) - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [11] 0 0
5 years
Secondary outcome [12] 0 0
Efficacy Progression-free survival (PFS) - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [12] 0 0
5 years
Secondary outcome [13] 0 0
Efficacy: Overall survival (OS) - To evaluate the efficacy of intrahepatic injection of talimogene laherparepvec in the overall population and by tumor type (non-hepatocellular carcinoma and hepatocellular carcinoma)
Timepoint [13] 0 0
5 years

Eligibility
Key inclusion criteria
Summary of Subject Eligibility Criteria:

Key

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 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.
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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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, 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Research Site - Liverpool
Recruitment hospital [2] 0 0
Research Site - North Sydney
Recruitment hospital [3] 0 0
Research Site - Southport
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
4215 - Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Austria
State/province [9] 0 0
Salzburg
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles
Country [11] 0 0
Belgium
State/province [11] 0 0
Edegem
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Bonn
Country [15] 0 0
Germany
State/province [15] 0 0
Reutlingen
Country [16] 0 0
Germany
State/province [16] 0 0
Tübingen
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seongnam-si, Gyeonggi-do
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Poland
State/province [19] 0 0
Gdansk
Country [20] 0 0
Spain
State/province [20] 0 0
Cataluña
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Switzerland
State/province [22] 0 0
Geneva 14
Country [23] 0 0
Switzerland
State/province [23] 0 0
Lausanne
Country [24] 0 0
Switzerland
State/province [24] 0 0
Winterthur
Country [25] 0 0
Switzerland
State/province [25] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 IV administration of pembrolizumab, in subjects with non-HCC liver metastases
from BC, CRC, gastroesophageal cancer (GEC), melanoma, NSCLC, 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
TNBC, hormone receptor positive breast cancer, CRC, CSCC, and 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.
Trial website
https://clinicaltrials.gov/show/NCT02509507
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02509507