Pembrolizumab With or Without Talimogene Laherparepvec in Squamous Cell Carcinoma of the Head and Neck

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2015-003011-38-GR
• Date of registration: 08/12/2015
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc.
• Public title: Pembrolizumab With or Without Talimogene Laherparepvec in Squamous Cell Carcinoma of the Head and Neck
• Scientific title: A Phase 1b/3 Multicenter, Randomized, Open-label Trial of Talimogene Laherparepvec in combination with Pembrolizumab for theTreatment of Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
• Date of first enrolment: 26/01/2016
• Target sample size: 490
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003011-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Brazil, Canada, European Union, France, Germany, Greece, Poland, Portugal, South Africa, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: IHQ medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female age = 18 years with histologically confirmed diagnosis of metastatic or recurrent SCCHN. Disease must be unsuitable for curative surgical resection and must not be amenable to curative radiotherapy.

• Disease must have progressed after treatment with a platinum-containing regimen

• Subject must be candidate for intralesional therapy administration defined as one or more of the following:
- At least 1 injectable cutaneous, subcutaneous, or nodal SCCHN tumor = 10 mm in longest diameter
- Multiple injectable SCCHN tumorsthat in aggregate have a longest diameter of = 10 mm

• Subject must have radiographically measurable disease

• ECOG performance status of 0 or 1

• Adequate organ function determined within 14 days prior to enrollment

• Phase 3: Subject has a tumor sample and no systemic therapy given since the biopsy or newly obtained biopsy from the primary or metastatic lesion that is adequate for PD-L1 assessment prior to randomization

• Phase 3: Have results from local testing of HPV of tumor specimen for oropharyngeal cancer defined as p16 IHC testing using the CINtec® assay and a 70% cutoff point

• Phase 1b: Subject has a tumor sample and no systemic therapy given since biopsy OR be willing to undergo newly obtained biopsy prior to the first dose of investigational product
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 392
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 98

Exclusion criteria:
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis, primary nasopharyngeal carcinoma

• Subject at risk of airway compromise in the event of postinjection tumor swelling/inflammation based on investigator judgment

• Greater than three lines of prior therapy for current malignancy and/or metastatic disease (Phase 3)

• History of other malignancy within the past 3 years, evidence of active, non-infectious pneumonitis, history of interstitial lung disease (ILD)

• Prior therapy with talimogene laherparepvec, pembrolizumab, other anti-PD-1, any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathway

• History or evidence of active autoimmune disease that has required systemic treatment in past 2 years, evidence of clinically significant immunosuppression

• Prior or active herpetic infection, require treatment with an antiherpetic drug, other than intermittent topical use

• Prior cancer therapy or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Metastatic Squamous Cell Carcinoma of the Head and Neck
MedDRA version: 18.1 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Talimogene Laherparepvec
Product Code: AMG 678
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Talimogene laherparepvec
Current Sponsor code: AMG 678
Other descriptive name: TALIMOGENE LAHERPAREPVEC
Concentration unit: PFU/ml plaque forming unit(s)/millilitre
Concentration type: equal
Concentration number: 10e6-

Product Name: Talimogene Laherparepvec
Product Code: AMG 678
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Talimogene laherparepvec
Current Sponsor code: AMG 678
Other descriptive name: TALIMOGENE LAHERPAREPVEC
Concentration unit: PFU/ml plaque forming unit(s)/millilitre
Concentration type: equal
Concentration number: 10e8-

Trade Name: Keytruda
Product Name: Keytruda
Product Code: L01XC18
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive name: Pembrolizumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Phase 1b: The DLT evaluation period is 6 weeks from the initial administration of study treatment.

Phase 3: Primary analysis for PFS and OS will be event-driven.

Secondary Objective: Phase 1b
• To evaluate the efficacy of talimogene laherparepvec in combination with Pembro as assessed by:
• ORR, BOR, DOR,DCR, PFS
• OS
• To evaluate the safety of T-Vec in combination with pembrolizumab as assessed by incidence of AEs and clinical laboratory abnormalities

Phase 3
• To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab, as compared to pembrolizumab alone, as assessed by:
- ORR, BOR; DOR, and DCR
- PFS
- 1-year, 2-year, and 3-year survival
• To evaluate the safety of talimogene laherparepvec in combination with pembrolizumab, as compared to pembrolizumab alone, as assessed by incidence of AEs and clinical laboratory abnormalities

Primary end point(s): Phase 1b:
• Subject incidence of DLT

Phase 3:
• PFS
• OS

Main Objective: Phase 1b: To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab in subjects with SCCHN.

Phase 3: To evaluate the efficacy, as assessed by PFS and OS, of treatment with talimogene laherparepvec in combination with pembrolizumab, as compared to pembrolizumab alone.

Secondary Outcome(s)

Secondary end point(s): Phase 1b:
• ORR (CR+PR), BOR, DOR, DCR, and PFS (response evaluation by investigator using irRECIST)
• OS
• Subject incidence of treatment-emergent and treatment-related adverse events and clinical laboratory abnormalities.

Phase 3:
• ORR, BOR; DOR, and DCR (response evaluation by blinded central assessment using conventional RECIST 1.1 and by investigator using irRECIST)
• PFS (response evaluation by investigator using irRECIST)
• 1-year, 2-year, and 3-year survival
• Subject incidence of treatment-emergent and treatment-related adverse events

Timepoint(s) of evaluation of this end point: For the phase 1b part of the study, the primary analysis will occur when the last subject enrolled has had the opportunity to complete the 9-week response assessment.

For the phase 3 part of the study, the timing for the primary analyses of PFS and OS will be event-driven.

The final analysis of the study will be conducted after the last subject enrolled in phase 3 has had the opportunity to complete the long-term follow-up.

Secondary ID(s)

20130232

2015-003011-38-GB

Source(s) of Monetary Support

Amgen Inc.

Merck Sharp and Dohme International GmbH

Ethics review

Status: Approved
Approval date: 26/01/2016
Contact: