Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer: a phase I dose-escalation study

Fiona Simpkins, Aurea Flores, Christina Chu, Jonathan S. Berek, Joseph Lucci, Sharon Murray, John Bauman, Herbert Struemper, Fiona Germaschewski, Zdenka Jonak, Olivia Gardner, John Toso, George Coukos

Research output: Contribution to journalArticle

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Abstract

Recombinant interleukin (IL)-18 (SB-485232) is an immunostimulatory cytokine, with shown antitumor activity in combination with pegylated liposomal doxorubicin (PLD) in preclinical models. This phase I study evaluated the safety, tolerability, and biologic activity of SB-485232 administered in combination with PLD in subjects with recurrent ovarian cancer. The protocol comprised four cycles of PLD (40 mg/m(2)) on day 1 every 28 days, in combination with SB-485232 at increasing doses (1, 3, 10, 30, and 100 μg/kg) on days 2 and 9 of each cycle, to be administered over five subject cohorts, followed by discretionary PLD monotherapy. Sixteen subjects were enrolled. One subject withdrew due to PLD hypersensitivity. Most subjects (82%) were platinum-resistant or refractory, and had received a median of three or more prior chemotherapy regimens. SB-485232 up to 100 μg/kg with PLD had an acceptable safety profile. Common drug-related adverse events were grade 1 or 2 (no grade 4 or 5 adverse events). Concomitant PLD administration did not attenuate the biologic activity of IL-18, with maximal SB-485232 biologic activity already observed at 3 μg/kg. Ten of 16 enrolled subjects (63%) completed treatment, whereas five (31%) subjects progressed on treatment. A 6% partial objective response rate and a 38% stable disease rate were observed. We provide pilot data suggesting that SB-485232 at the 3 μg/kg dose level in combination with PLD is safe and biologically active. This combination warrants further study in a phase II trial.

Original languageEnglish (US)
Pages (from-to)168-178
Number of pages11
JournalCancer immunology research
Volume1
Issue number3
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

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Interleukin-18
Ovarian Neoplasms
Safety
liposomal doxorubicin
Platinum
Drug-Related Side Effects and Adverse Reactions
Hypersensitivity
Cytokines
Drug Therapy
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer : a phase I dose-escalation study. / Simpkins, Fiona; Flores, Aurea; Chu, Christina; Berek, Jonathan S.; Lucci, Joseph; Murray, Sharon; Bauman, John; Struemper, Herbert; Germaschewski, Fiona; Jonak, Zdenka; Gardner, Olivia; Toso, John; Coukos, George.

In: Cancer immunology research, Vol. 1, No. 3, 01.09.2013, p. 168-178.

Research output: Contribution to journalArticle

Simpkins, F, Flores, A, Chu, C, Berek, JS, Lucci, J, Murray, S, Bauman, J, Struemper, H, Germaschewski, F, Jonak, Z, Gardner, O, Toso, J & Coukos, G 2013, 'Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer: a phase I dose-escalation study', Cancer immunology research, vol. 1, no. 3, pp. 168-178. https://doi.org/10.1158/2326-6066.CIR-13-0098
Simpkins, Fiona ; Flores, Aurea ; Chu, Christina ; Berek, Jonathan S. ; Lucci, Joseph ; Murray, Sharon ; Bauman, John ; Struemper, Herbert ; Germaschewski, Fiona ; Jonak, Zdenka ; Gardner, Olivia ; Toso, John ; Coukos, George. / Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer : a phase I dose-escalation study. In: Cancer immunology research. 2013 ; Vol. 1, No. 3. pp. 168-178.
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AU - Berek, Jonathan S.

AU - Lucci, Joseph

AU - Murray, Sharon

AU - Bauman, John

AU - Struemper, Herbert

AU - Germaschewski, Fiona

AU - Jonak, Zdenka

AU - Gardner, Olivia

AU - Toso, John

AU - Coukos, George

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