Einleitung wieder einblenden
NCT02509507

Trial to Evaluate the Safety of Talimogene Laherparepvec Injected Into Tumors Alone and in Combination With Systemic Pembrolizumab MK-3475-611/Keynote-611

Datenbasis: WHO (Import vom 27.09.2020)
Geändert: 27.09.2020
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Hepatocellular Carcinoma;Liver Metastases;Cutaneous or Subcutaneous Lymph Node;Liver Tumors

Interventions (Datenquelle: WHO)

Drug: Talimogene Laherparepvec;Drug: Pembrolizumab

Inclusion/Exclusion Criteria (Datenquelle: WHO)


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, PR 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 Part 1 Group B cohort 6b and Part 2 Arm VII, subjects must have a diagnosis of
hepatitis B and/or C. Those with hepatitis B must be on hepatitis 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. 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 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 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 from BC,
NSCLC, RCC, CRC, GEC, or melanoma. 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 (Arms I-VI). 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. They must not require
concomitant treatment with warfarin. 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.

Weitere Angaben zur Studie im WHO-Primärregister

https://clinicaltrials.gov/show/NCT02509507

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02509507

Weitere Informationen zur Studie

Registrationsdatum der Studie

10.07.2015

Einschluss der ersten teilnehmenden Person

05.02.2016

Rekrutierungsstatus

Recruiting

Wissenschaftlicher Titel (Datenquelle: WHO)

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)

Studientyp (Datenquelle: WHO)

Interventional

Design der Studie (Datenquelle: WHO)

Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Datenquelle: WHO)

Phase 1

Primäre Endpunkte (Datenquelle: WHO)

Subject incidence DLTs separately in Group A and B observed in monotherapy and combination cohorts and in each tumor type seperately in Part 2;To evaluate in Part 2 ORR per modified irRC-RECIST separately by tumor type (BC, CRC, GEC, melanoma, NSCLC, RCC, and HCC)

Sekundäre Endpunkte (Datenquelle: WHO)

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;Safety: To estimate the incidence of detectable talimogene laherparepvec DNA in blood and urine;Safety: To estimate the incidence of clearance of talimogene laherparepvec DNA from blood and urine;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;Safety: To estimate the incidence of talimogene laherparepvec DNA detection in lesions suspected to be herpetic in origin;Efficacy: Objective response rate (ORR);Efficacy: Best overall response (BOR);Efficacy: Durable response rate (DRR);Efficacy: Duration of response (DOR);Efficacy: Response in injected and uninjected lesions;Efficacy: Disease control rate (DCR);Efficacy Progression-free survival (PFS);Efficacy: Overall survival (OS)

Kontakt für Auskünfte (Datenquelle: WHO)

Please refer to primary and secondary sponsors

Ergebnisse der Studie (Datenquelle: WHO)

Zusammenfassung der Ergebnisse

noch keine Angaben verfügbar

Link zu den Ergebnissen im Primärregister

noch keine Angaben verfügbar

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten

noch keine Angaben verfügbar

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Australia, Austria, Belgium, Germany, Korea, Poland, Republic of, Spain, Switzerland, United States

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

MD;Amgen Call Center
Amgen
866-572-6436
medinfo@amgen.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

MD;Amgen Call Center
Amgen
866-572-6436
medinfo@amgen.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Amgen

Weitere Sponsoren (Datenquelle: WHO)

Merck Sharp & Dohme Corp.

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

2014-005386-67
20140318