Clinical Trial 18758

Cancer Type:
Interventions:PF-04518600; PF-05082566 (utomilumab)

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Alberto Chiappori

Overview

Study Title

A Phase 1, Open-Label Dose Escalation Study of PF-04518600 as a Single Agent and in Combination with PF-05082566 in Patients with Selected Locally Advanced or Metastatic Carcinomas

Summary

To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination with PF-05082566 in participants with select advanced or metastatic carcinoma.

Objective

Objectives for Part A1 Monotherapy Dose Escalation - Primary Objective: *To assess safety, and tolerability at increasing dose levels of PF-04518600 in patients with selected advanced or metastatic solid tumors in order to establish the MTD. Objectives for Part A2 Monotherapy Dose Expansion - Primary Objectives: *To establish the recommended phase 2 dose (RP2D) of PF-04518600 in patients with selected advanced or metastatic solid tumors. *To further characterize the safety and tolerability of PF-04518600 in patients with selected advanced or metastatic solid tumors. Objectives for Part B1 Combination Therapy Dose Escalation - Primary Objective: *To assess safety and tolerability at increasing dose levels of PF-04518600 in combination with PF-05082566 in patients with selected advanced or metastatic solid tumors and to estimate MTD of the combination. Objectives for Part B2 Combination Therapy Dose Expansion - Primary Objective: *To further assess safety and tolerability of PF-04518600 in combination with PF-05082566 in patients with selected advanced or metastatic solid tumors in order to establish RP2D for the combination.

Inclusion Criteria

  • Age 18 years or older
  • Part A1 only: Patients with histological or cytological diagnosis of head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), melanoma, or clear cell renal cell carcinoma (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 HCC who have had 0 to 2 prior lines of systemic therapy (progressed or intolerant to approved HCC standard of care treatment).
  • Part B1 only: Patients with histological or cytological diagnosis of non-small cell lung cancer (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: Ocular melanoma; and have received no more than one line of systemic therapy for metastatic disease. Patients must not have received immune modifying agents (e.g., anti PD-L1, anti PD-1, anti CTLA4, TNF agonist, etc.) for metastatic disease - OR - Cutaneous/acral melanoma; and have 1) only previously received systemic therapy for advanced/metastatic disease with the following therapies: BRAF and MEK inhibitors, anti PD-L1, anti PD-1, or anti-CTLA4 and 2) have received checkpoint inhibitor (anti PD-L1, anti PD-1, or anti-CTLA4) based treatment as most recent line of therapy on which disease progressed, as long as progression did not occur in the first 3 months of receiving checkpoint inhibitor treatment. Arm 2 only: Histological or cytological diagnosis of NSCLC. Patients must have: 1) previously received prior anti-PD-L1 or anti-PD-1 mAb as most recent therapy, AND 2) did not have progressive disease as best overall response on recent PD-L1/PD-1 therapy (ie, stable disease 3 months, PR, or CR), AND 3) who subsequently progressed on anti-PD-L1 or anti-PD-1 mAb. Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function.

  • Exclusion Criteria

  • Brain metastases requiring steroids
  • Major surgery, radiation therapy, 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)