Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566
Condition: Neoplasms
MeSH terms: Neoplasms
Intervention: PF-04518600; PF-04518600; PF-04518600 plus PF-05082566; PF-04518600 plus PF-05082566
Intervention description: Part A1 - PF-04518600 will be administered intravenously every 14 days in cohorts of 2 or more patients starting at a dose of 0.01 mg/kg. Increases in dose will continue until MTD is determined; Part A2 - patients with hepatocellular carcinoma will be randomized to receive treatment with PF-04518600 at various doses administered intravenously; Part B1 -In cohorts of 2 or more patients, PF-04518600 will be administered intravenously every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered intravenously 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined.; Part B2 - patients with select tumor types (ocular melanoma, cutaneous/acral melanoma or non-small cell lung cancer) will be treated at dose levels based on the OBD selected in Part 1.
Intervention MeSH terms: Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: Open-label
Enrollment: 174.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; PF-04518600; PF-05082566; solid tumors; tumors; neoplasm metastasis; Phase 1; hepatocellular carcinoma; HCC; liver cancer; ocular melanoma; melanoma; clear cell renal cell carcinoma; RCC; kidney cancer; head and neck squamous cell carcinoma; HNSCC; head and neck cancer; cervical cancer; cancer of the cervix; gastric cancer; stomach cancer; non small cell lung cancer; NSCLC; lung cancer; urothelial bladder carcinoma; bladder cancer; OX40; 4-1BB

Summary:

      To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in
      combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in
      order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC,
             melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy,
             for which no standard therapy is available or who decline standard therapy.

          -  Part A2 only: Patients with histological or cytological diagnosis of
             advanced/metastatic HCC who are treatment naïve and have declined standard of care, or
             have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is
             allowed.

          -  Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC,
             melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary
             bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who
             progressed on or are intolerant to standard therapy, for which no standard therapy is
             available, or who decline standard therapy.

          -  Part B2

        Arm 1 only:

          1. Ocular melanoma patients with advanced/metastatic disease, or

          2. Cutaneous/acral melanoma patients with advanced/metastatic disease who have received
             checkpoint inhibitor (anti PD L1, anti PD 1, or anti CTLA4) based treatment on which
             disease progressed. [Note: Checkpoint inhibitor may have been part of a combination
             therapy, as long as the combination did not contain OX40 or 4 1BB agonist.] Any
             questions on prior treatment may be discussed with the Sponsor.

        Arm 2 only:

          -  Histological or cytological diagnosis of NSCLC with advanced/metastatic disease.
             Patients must have previously received prior anti PD L1 or anti PD 1 mAb on which
             disease progressed. [Note: Previous anti PD L1 or anti PD 1 mAb may have been part of
             a combination therapy, eg, in combination with chemotherapy, as long as the
             combination did not contain OX40 or 4 1BB agonist.]

          -  Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function

        Exclusion Criteria:

          -  Brain metastases requiring steroids

          -  Major surgery, Radiation therapy within 4 weeks of starting study treatment (except:
             palliative radiotherapy to a limited field is allowed after consultation with
             sponsor's medical monitor at any time during study participation, including during
             screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6
             weeks for mitomycin C or nitrosoureas)

          -  Active and clinically significant bacterial, fungal, or viral infection

          -  History of active autoimmune disorders

          -  History of immune-mediated adverse events requiring immunosuppressive therapy or were
             grade 3 or higher related to prior immune-modulatory therapy

          -  Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)

          -  Prior anthracycline treatment and at risk of cardiac failure (New York Heart
             Association Class 2)