| 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 |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 20.0 |
| 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) |
|
| 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 recurrent or metastatic SCCHN.
Phase 3: To evaluate the efficacy, as assessed by overall survival (OS), of treatment with talimogene laherparepvec with pembrolizumab versus
placebo with pembrolizumab in subjects with recurrent or metastatic SCCHN. |
|
| E.2.2 | Secondary objectives of the trial |
Phase 1b
• To evaluate the efficacy of talimogene laherparepvec in combination with pembrolizumab as assessed by:
- iORR, iCRR, iBOR, iDOR, iDCR, iPFS, response evaluation by investigator using immune-related irRECIST
- OS
• To evaluate the safety of talimogene in combination with pembro as assessed by incidence of adverse events and laboratory abnormalities.
Phase 3
• To evaluate the efficacy of talimogene with pembro versus placebo with pembro, as assessed by:
- ORR and PFS (response evaluation by investigator using RECIST v1.1)
- iORR and iPFS (response evaluation by investigator using irRECIST)
- iCRR, iBOR; iDOR, and iDCR (response evaluation by investigator using irRECIST)
- CRR, BOR, DOR, and DCR (response evaluation by investigator using RECIST v1.1)
- 1 year, 2 year, and 3 year survival
- Subject incidence of treatment-emergent and treatment-related AEs
• To evaluate PRO as assessed by the EORTC QLQ-C30 GHS/QoL subscale. |
|
| 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 of the oral cavity, oropharynx, hypopharynx, or larynx. 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 cutaneous, subcutaneous, or nodal SCCHN tumors that 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
• PTT or aPTT ≤ 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and PTT/aPTT is within therapeutic range of intended use of anticoagulants. Female subject of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment. If urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Phase 1b: Subject has a formalin fixed paraffin-embedded tumor sample (within 6 months prior to week 0, day 1 of the study, or newly obtained biopsy) from the primary or metastatic lesion that must be submitted within 4 weeks of enrollment for PD-L1, HPV-testing of oropharyngeal cancer (if not performed locally) and biomarker analyses.
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 |
|
| 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
• Phase 3: Greater than three lines of prior therapy for current malignancy and/or metastatic disease
• History of other malignancy within the past 3 years, 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 the 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, targeted 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.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Subjects with tumor that directly contacts or encases a major blood vessel AND there is ulceration and/or fungation onto the skin surface.
• History of re-irradiation to a field which includes the carotid arteries. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase 1b:
• Subject incidence of DLT
Phase 3:
• OS
|
|
| 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 OS will be event-driven. |
|
| E.5.2 | Secondary end point(s) |
Phase 1b:
• iORR (iCR+iPR), iCRR, iBOR, iDOR, iDCR, and iPFS (response evaluation
by investigator using irRECIST)
• OS
• Subject incidence of treatment-emergent and treatment-related
adverse events and laboratory abnormalities.
Phase 3:
• ORR and PFS (response evaluation by investigator using RECIST v1.1)
• iORR and iPFS (response evaluation by investigator using irRECIST)
• iCRR, iBOR; iDOR, and iDCR (response evaluation by investigator using
irRECIST)
• CRR, BOR, DOR, and DCR (response evaluation by investigator using
RECIST v1.1)
• 1-year, 2-year, and 3-year survival
• Subject incidence of treatment-emergent and treatment-related
adverse events
• Summary scores at each assessment and changes from baseline of
PROs as assessed by QLQ-C30 GHS/QoL subscale.treatment-related adverse events
• Summary scores at each assessment and changes from baseline of PROs as assessed by QLQ-C30 GHS/QoL subscale. |
|
| 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 OS will be event-driven based on the FAS(G)
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. |
|
| 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 |
|
| 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) |
|
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| 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 | 4 |
| 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 |
|
| 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
|
| 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. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
