Talimogene Laherparepvec With Pembrolizumab for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY232 / KEYNOTE-137)
Condition: Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Talimogene Laherparepvec; Pembrolizumab
Intervention description: The initial dose of talimogene laherparepvec is up to 8.0 mL of 10⁶ PFU/mL. Subsequent doses of talimogene laherparepvec are up to 8.0 mL of 10⁸ PFU/mL.; Administered as a 30-minute intravenous infusion at a dose of 200 mg Q3W
Intervention MeSH terms: Pembrolizumab; Talimogene laherparepvec
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: For Phase 1b there are no 'maskings' as it's open-label.
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Recurrent Metastatic Squamous Cell Carcinoma Head and Neck

Summary:

      The primary objective of this study was to evaluate the safety, as assessed by incidence of
      dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab
      in adults with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).
    

Eligibility criteria:

        Inclusion Criteria

          -  Male or female age ≥ 18 years at the time of informed consent

          -  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 and
             should be defined as one of the following:

             i. disease progression or recurrence between 3 to 6 months of prior curatively
             intended multimodal therapy (which includes platinum therapy) for locoregionally
             advanced SCCHN.

        ii. disease progression or recurrence after prior platinum therapy in the recurrent or
        metastatic setting Note: This criterion is only applicable for subjects who have not had
        treatment in the recurrent/metastatic setting

          -  Subject must be candidate for intralesional therapy administration defined as one or
             more of the following:

             i. at least 1 injectable cutaneous, subcutaneous, or nodal SCCHN tumor ≥ 10 mm in
             longest diameter ii. multiple injectable cutaneous, subcutaneous, or nodal SCCHN
             tumors that in aggregate have a longest diameter of ≥ 10 mm Note: Mucosal surfaces of
             tumor lesions and visceral metastases should not be injected.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Adequate organ function determined within 14 days prior to enrollment

          -  Female subject of childbearing potential must have a negative pregnancy test within 72
             hours prior to enrollment.

          -  Other Inclusion Criteria May Apply

        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: Previous treatment with 3 or more systemic regimens given for recurrent
             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 (ie, with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs).

          -  Evidence of clinically significant immunosuppression

          -  Active herpetic skin lesions or prior complications of herpetic infection (eg,
             herpetic keratitis or encephalitis).

          -  Requires intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir),
             other than intermittent topical use.

          -  Prior chemotherapy, radiotherapy, biological cancer therapy, targeted therapy, or
             major surgery within 28 days prior to enrollment or has not recovered to Common
             Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from adverse event
             due to cancer therapy administered more than 28 days prior to enrollment.

          -  Expected to require other cancer therapy while on study with the exception of local
             palliative radiation treatment to the site of bone and other metastasis.

          -  Known human immunodeficiency virus (HIV) disease.

          -  Has acute or chronic active hepatitis B virus or hepatitis C virus infection or
             received treatment with nucleotide analogs such as those used in the treatment of
             hepatitis B virus (eg, lamivudine, adefovir, tenofovir, telbivudine, entecavir),
             ribavirin, or interferon alpha within 12 weeks of initiation of study treatment.

          -  Received live vaccine within 28 days prior to enrollment.

          -  Subject is pregnant or breast-feeding, or expecting to conceive or father children
             within the duration of the trial

          -  Female subject of childbearing potential or male subject of reproductive potential who
             is unwilling to use acceptable method(s) of effective contraception during study
             treatment and through 3 months after the last dose of talimogene laherparepvec/placebo
             or 4 months after the last dose of pembrolizumab, whichever is later.

          -  Sexually active subjects or their partners unwilling to use male or female latex
             condom to avoid potential viral transmission during sexual contact while on treatment
             and within 30 days after treatment with talimogene laherparepvec/placebo.

          -  Subject who is unwilling to minimize exposure with his/her blood or other body fluids
             to individuals who are at higher risks for herpes simplex virus type 1 (HSV-1)-induced
             complications (eg, immunosuppressed individuals, HIV-positive individuals, pregnant
             women, or children under the age of 1 year) during talimogene laherparepvec treatment
             and through 30 days after the last dose of talimogene laherparepvec

          -  Has history of (non-infectious) pneumonitis that required steriods 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

          -  Other Exclusion Criteria May Apply