A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma or Other Solid Tumors
Condition: Part 1; MELANOMA; SCCHN; OVCA; SARCOMA; OTHER SOLID TUMORS; Part 1 and 2; NSCLC; UROTHELIAL CARCINOMA
MeSH terms: Carcinoma; Melanoma; Sarcoma; Head and Neck Neoplasms; Carcinoma, Transitional Cell
Intervention: PF-06801591; PF-06801591
Intervention description: IV every 21 days (Part 1); 300 mg SC every 28 days (Part 1 and 2)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
Enrollment: 147.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: efficacy; safety; pharmacokinetics; pharmacodynamics; open label; dose response; multiple ascending dose; immunogenicity; recommended phase 2 dose; subcutaneous

Summary:

      Protocol B8011001 is a Phase 1, open-label, multi-center, multiple-dose, dose escalation and
      expansion, safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of PF-06801591 in
      previously treated adult patients with locally advanced or metastatic melanoma, SCCHN,
      ovarian carcinoma, sarcoma, NSCLC, urothelial carcinoma or other solid tumors. This is a 2
      Part study whereby the safety and tolerability of increasing dose levels of intravenous (IV)
      or subcutaneous (SC) PF-06801591 was assessed in Part 1. Part 2 expansion is designed to
      further evaluate the safety and efficacy of SC PF-06801591 in patients with NSCLC or
      urothelial carcinoma as well as confirm the recommended Phase 2 dose.
    

Eligibility criteria:

        Inclusion Criteria (Part 2 Only):

          -  Histological or cytological diagnosis of locally advanced or metastatic NSCLC or
             urothelial carcinoma who have progressed on or were intolerant to standard of care
             systemic therapy, or for whom standard of care systemic therapy was refused (refusal
             must be documented) or unavailable.

          -  No prior treatment with anti-PD-1 or anti-PD-L1 therapy.

          -  NSCLC patients whose tumor is not known to have ALK or EGFR mutations must have
             progressed on or after no more than 1 prior line of platinum-containing systemic
             therapy or were intolerant or refused standard of care systemic therapy.

          -  NSCLC patients whose tumor is known to have ALK or EGFR mutation must have received
             prior systemic therapies that only include 1 or more lines of ALK or EGFR targeting
             drugs and chemotherapy limited to 1 line of a platinum-based regimen and they must
             have progressed on or after both types of therapies.

          -  Urothelial carcinoma patients must have received up to 2 lines of prior systemic
             therapy and progressed on or after, experienced disease recurrence within 12 months of
             neoadjuvant or adjuvant treatment, were intolerant to, ineligible or refused
             platinum-containing systemic therapy. If urothelial cancer patients are treatment
             naïve and eligible for platinum-containing systemic therapy but are refusing platinum
             chemotherapy, they must also be documented to have previous PD-L1 high status.

          -  Provide archived tumor tissue sample taken within the past 2 years or provide a fresh
             tumor biopsy sample.

          -  At least one measurable lesion as defined by RECIST version 1.1.

          -  Adequate renal, liver, thyroid and bone marrow function.

          -  Performance status 0 or 1.

          -  Patient is capable of receiving study treatment for at least 8 weeks.

        Exclusion Criteria (Part 2 Only)

          -  Active brain or leptomeningeal metastases.

          -  Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes
             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger are permitted to enroll. Diagnosis of
             prior immunodeficiency or organ transplant requiring immunosuppressive therapy or
             prior allogeneic bone marrow or hematopoietic stem cell transplant.

          -  Patients with a condition requiring systemic treatment with either corticosteroids
             (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration. Inhaled or topical steroids, and adrenal
             replacement doses >10 mg daily prednisone equivalents are permitted in the absence of
             active autoimmune disease.

          -  Patients with a history of interstitial lung disease, non-infectious pneumonitis, or
             active pulmonary tuberculosis. Those with active lung infections requiring treatment
             are also excluded.

          -  History of Grade ≥3 immune mediated AE (including AST/ALT elevations that where
             considered drug related and cytokine release syndrome) that was considered related to
             prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory
             agents, etc.) and required immunosuppressive therapy.

          -  Active hepatitis B or C, HIV/AIDS.

          -  Other potentially metastatic malignancy within past 5 years.