E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Squamous Cell Carcinoma of the Head and Neck |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1b:
• Subject incidence of DLT
Phase 3:
• PFS
• OS
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E.5.1.1 | 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. |
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E.5.2 | 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 |
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E.5.2.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1b to evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT) |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
European Union |
South Africa |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study for each subject is defined as the date the subject withdraws full consent from the study, completes the safety follow-up visit or final long-term follow-up visit (whichever is later) or death. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |