Patient case: 73-year-old male with melanoma; genetic feature: tumor cells negative for PD-L1 expression

Clinical trial: A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Summary: This is a phase 1b/2, open-label, multicenter trial designed to evaluate the safety, tolerability, biologic activity, and preliminary efficacy of intratumoral SD 101 injections in combination with intravenous pembrolizumab in patients with metastatic melanoma or recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
  Phase 1 of this trial is a modified 3+3 dose escalation study evaluating escalating or intermediate dose levels of SD-101 given with a fixed dose of pembrolizumab in patients with metastatic melanoma.
  Phase 2 of this study will consist of 4 expansion cohorts to further evaluate the efficacy and safety of SD-101 given in combination with pembrolizumab in specific melanoma and HNSCC populations: For each of the indications in melanoma and HNSCC 2 separate cohorts will be recruited, those who are anti-programmed death receptor-1/ligand 1 (anti-PD-1/L1) therapy naïve and those who have progressive disease (PD) while receiving anti-PD-1/L1 therapy.

Detailed description: This study will be conducted in two parts.
  Phase 1b is dose escalation in which patients are tested with SD-101 at various doses in combination with 200 mg pembrolizumab in patients with metastatic melanoma.
  Phase 2 will consist of 4 expansion cohorts to evaluate the efficacy and safety of SD-101 given in combination with 200 mg pembrolizumab in specific melanoma populations and recurrent or metastatic HNSCC.

Eligibility: Inclusion Criteria: Phase 2 Melanoma patients
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
  -  Provide tissue for PD-L1 biomarker analysis from a newly obtained biopsy obtained within 28 days of enrollment.
  -  Must have adequate organ function as indicated by laboratory results.
  -  Histologically or cytologically confirmed unresectable in-transit (stage IIIc) or metastatic (stage IV) melanoma.
  -  At least 2 sites of measurable disease of which 1 must be palpable or visualized by ultrasound and easily accessible to multiple intratumoral injections. The injected lesions must qualify as a measurable target lesion per RECIST 1.1.
  -  Metastatic melanoma patients with progressive disease (PD) while receiving anti-PD-1/L1 therapy must have documented PD per RECIST 1.1 while receiving a prior anti-PD-1/L1 therapy and must have received a prior anti-PD-1/L1 agent within 6 weeks of study enrollment.
  Inclusion Criteria: Phase 2 HNSCC patients
  -  Histologically or cytologically confirmed recurrent or metastatic HNSCC that could not be treated with curative intent.
  -  Have at least 1 measurable site of disease (target lesion per RECIST 1.1, which must be accessible and amenable to multiple intratumoral injections. If superficial, the lesion must measure at least 10 mm in diameter, measured by calipers, and be documented photographically.
  -  Recurrent or metastatic HNSCC patients with PD while receiving anti-PD-1/L1 therapy must have documented PD per RECIST 1.1 while receiving anti-PD-1/L1 therapy and must have received anti-PD-1/L1 agent within 6 weeks of study enrollment.
  Exclusion Criteria: (Phase 2 Melanoma and HNSCC patients)
  -  Is expected to require any other form of anti-cancer therapy while in the trial.
  -  Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  -  History of or current uveal or ocular melanoma.
  -  Active infection including cytomegalovirus.
  -  Active autoimmune disease requiring systemic treatment in the past 2 years or a disease that requires immunosuppressive medication including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  -  Current pneumonitis or history of (non-infectious) pneumonitis that required steroids.
  -  Known active central nervous system metastases or carcinomatous meningitis.
  -  Use of any investigational agent within the last 28 days prior to study enrollment.
  -  Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  -  Any known additional malignancy that is progressing or requires active treatment, except for melanoma and HNSCC.

Relevance to patient case: not relevant