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A randomized phase II/III study of naptumomab estafenatox + IFNα versus IFNα in renal cell carcinoma : Final analysis with baseline biomarker subgroup and trend analysis

Hawkins, Robert E.; Gore, Martin; Shparyk, Yaroslav; Bondar, Vladimir; Gladkov, Oleg; Ganev, Tosho; Harza, Mihai; Polenkov, Serhii; Bondarenko, Igor and Karlov, Petr, et al. (2016) In Clinical Cancer Research 22(13). p.3172-3181
Abstract

Purpose: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFNα versus IFN in metastatic renal cell carcinoma (RCC). Experimental Design: In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 μg/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s. c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS). Results: This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the... (More)

Purpose: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFNα versus IFN in metastatic renal cell carcinoma (RCC). Experimental Design: In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 μg/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s. c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS). Results: This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile. Conclusions: The study did not meet its primary endpoint. Nap + IFN has an acceptable safety profile, and results from post hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker-defined RCC patient subgroup. The results warrant further studies with Nap in this subgroup.

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Clinical Cancer Research
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22
issue
13
pages
10 pages
publisher
American Association for Cancer Research
external identifiers
  • scopus:84977097812
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-15-0580
language
English
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no
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2c71a89a-d67d-451b-9f80-364fda9eab9e
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2016-07-20 12:04:20
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2017-09-17 09:20:07
@article{2c71a89a-d67d-451b-9f80-364fda9eab9e,
  abstract     = {<p>Purpose: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFNα versus IFN in metastatic renal cell carcinoma (RCC). Experimental Design: In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 μg/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s. c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS). Results: This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile. Conclusions: The study did not meet its primary endpoint. Nap + IFN has an acceptable safety profile, and results from post hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker-defined RCC patient subgroup. The results warrant further studies with Nap in this subgroup.</p>},
  author       = {Hawkins, Robert E. and Gore, Martin and Shparyk, Yaroslav and Bondar, Vladimir and Gladkov, Oleg and Ganev, Tosho and Harza, Mihai and Polenkov, Serhii and Bondarenko, Igor and Karlov, Petr and Karyakin, Oleg and Khasanov, Rustem and Hedlund, Gunnar and Forsberg, Göran and Nordle, Örjan and Eisen, Timothy},
  issn         = {1078-0432},
  language     = {eng},
  month        = {07},
  number       = {13},
  pages        = {3172--3181},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {A randomized phase II/III study of naptumomab estafenatox + IFNα versus IFNα in renal cell carcinoma : Final analysis with baseline biomarker subgroup and trend analysis},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-15-0580},
  volume       = {22},
  year         = {2016},
}