Phase 1 study of AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adults with advanced solid tumors

Alain C. Mita, Chris H. Takimoto, Monica Mita, Anthony Tolcher, Kamalesh Sankhala, John Sarantopoulos, Manuel Valdivieso, Leslie Wood, Erik Rasmussen, Yu Nien Sun, Z. Don Zhong, Michael B. Bass, Ngoc Diep Le, Patricia LoRusso

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Purpose: To evaluate the safety, pharmacokinetics, and antitumor activity of AMG 386, an investigational selective angiopoietin 1/2-neutralizing peptibody, in combination with FOLFOX-4 (F), carboplatin/paclitaxel (C/P), or docetaxel (D), in adult patients with advanced solid tumors. Experimental Design: Three cohorts of patients (F, n = 6; C/P, n = 8; D, n = 12) received one full cycle of chemotherapy alone during the pretreatment phase, followed by administration of AMG 386 10 mg/kg i.v. weekly in combination with chemotherapy until disease progression or intolerance. Safety and tolerability, tumor response, pharmacokinetic profiles, and biomarkers were assessed. Results: Twenty-six patients were enrolled; 22 received treatment with AMG 386. No dose-limiting toxicities or grade 3 or 4 adverse events related to AMG 386 were reported. The most common adverse events were diarrhea and hypomagnesemia (n = 3 each). One patient developed grade 2 hypertension and one had grade 1 subconjunctival eye hemorrhage. No neutralizing antibodies to AMG 386 were detected. There were no pharmacokinetic interactions between AMG 386 and F, C/P, or D. One patient receiving AMG 386 plus C/P for bladder cancer refractory to gemcitabine/cisplatin had a complete response at week 8. The remaining best tumor responses were partial response (n = 3, one from each cohort), stable disease ≥8 weeks (n = 13), and progressive disease (n = 1). Conclusions: Weekly administration of AMG 386 in combination with three common chemotherapy regimens was well tolerated in patients with advanced solid tumors. No pharmacokinetic interactions between AMG 386 and any of the tested chemotherapy regimens were noted. Promising antitumor activity was observed with all three treatment combinations.

Original languageEnglish (US)
Pages (from-to)3044-3056
Number of pages13
JournalClinical Cancer Research
Volume16
Issue number11
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • General Medicine

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