Safety and Efficacy of PF-3512676 for the Treatment of Stage IV Renal Cell Carcinoma: An Open-Label, Multicenter Phase I/II Study

John A. Thompson, Timothy Kuzel, Beverly J. Drucker, Walter Urba, Ronald Bukowski

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Purpose: Single-agent PF-3512676 (agatolimod), a Toll-like receptor 9 agonist, was examined in an open-label, single-arm, multicenter phase I/II study to determine its maximum tolerated dose (MTD), safety profile, antitumor activity, pharmacokinetics, and immunologic effects in patients with advanced metastatic renal cell carcinoma (RCC). Patients and Methods: PF-3512676 was administered subcutaneously weekly for up to 24 weeks to 39 adults with stage IV RCC. Patients were excluded if they had received previous therapy other than surgery. Phase I dose escalation began at 0.08 mg/kg, with phase II expansion to 20 patients to estimate objective response rates at 0.16 mg/kg. Doses were subsequently escalated to 0.81 mg/kg according to the phase I design. Results: An MTD was not reached. One patient who received 0.54 mg/kg had dose-limiting toxicities (grade 3 nonhematologic adverse events [AEs], including anorexia). The most commonly reported AEs were flu-like symptoms and local injection-site reactions of mild-to-moderate severity. The most commonly reported serious AE was grade 3 fatigue in 4 patients (10%). Grade 4 AEs included anemia, exacerbated dyspnea, and polyarthralgia in 1 patient each. Two patients (5%), 1 each in the 0.16-mg/kg and 0.54-mg/kg cohorts, achieved a partial response. Both responses were durable (35 and 40 months). Conclusion: This was the first study to examine PF-3512676 safety and antitumor activity in patients with advanced RCC. Single-agent treatment was tolerable. At the doses tested, PF-3512676 had modest antitumor activity. Additional studies in combination with other agents or at higher monotherapy doses might be warranted.

Original languageEnglish (US)
Pages (from-to)E58-E65
JournalClinical Genitourinary Cancer
Issue number3
StatePublished - Jan 1 2009


  • Immunotherapy
  • Inducible protein-10
  • Maximum tolerated dose
  • Toll-like receptor 9

ASJC Scopus subject areas

  • Oncology
  • Urology


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