TY - JOUR
T1 - A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma
AU - Voss, Martin H.
AU - Bhatt, Rupal S.
AU - Vogelzang, Nicholas J.
AU - Fishman, Mayer
AU - Alter, Robert S.
AU - Rini, Brian I.
AU - Beck, J. Thaddeus
AU - Joshi, Monika
AU - Hauke, Ralph
AU - Atkins, Michael B.
AU - Burgess, Earle
AU - Logan, Theodore F.
AU - Shaffer, David
AU - Parikh, Rahul
AU - Moazzam, Nauman
AU - Zhang, Xiaosha
AU - Glasser, Chad
AU - Sherman, Matthew L.
AU - Plimack, Elizabeth R.
N1 - Funding Information:
Martin H. Voss received support in part through National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748 for work performed as part of the current study and has received grants from Bristol-Myers Squibb, Genentech, and Pfizer; acted as a paid consultant for Alexion Pharmaceuticals, Bayer, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, GlaxoSmithKline, Natera, Novartis, and Pfizer; and received travel expenses from Novartis, Takeda, and Eisai for work performed outside of the current study. Rupal S. Bhatt has a patent (ALK-Fc exhibits activity in Renal cancer murine xenografts as a single agent and in combination with VEGFR inhibition) licensed to Beth Israel Deaconess Medical Center and has received research funding from Acceleron Pharma Inc for work performed outside of the current study. Nicholas J. Vogelzang has acted as a member of the speakers’ bureau for Bristol-Myers Squibb, Exelixis, and Roche and has acted as a paid consultant for Novartis, Pfizer, and Cerulean for work performed outside of the current study. Mayer Fishman has received honoraria and speaking fees from Exelixis, Pfizer, Prometheus, and Ipsen; has acted as a member of the Data Safety Monitoring Board for Immatics; has received research funding from Acceleron Pharma Inc; has received research funding from and acted as a paid consultant for Alkermes; has received research funding from Bristol-Myers Squibb and Calithera Biosciences; has received research funding from and acted as a paid consultant for Eisai; has received research funding from Merck and Nektar; has received research funding from and acted as a paid consultant for Pfizer; has received research funding from Prometheus; and has acted as a paid consultant for Novartis for work performed outside of the current study. Robert S. Alter has received honoraria and speaking fees from AstraZeneca; has received honoraria and speaking fees from and acted as a paid consultant for Astellas, Eisai, and Pfizer; and has received honoraria and speaking fees from Merck, Genentech, Exelexis, Bayer, Bristol-Myers Squibb, Janssen, Sanofi, and Amgen for work performed outside the current study. Brian I. Rini has received research funding from and acted as a paid consultant for Pfizer for work performed outside of the current study. J. Thaddeus Beck has received research funding to his institution from Alexion, Novartis, Lilly, Genentech, AstraZeneca, Calithera Biosciences, Pfizer, Acceleron Pharma Inc, Janssen, Bristol-Myers Squibb, Merck Serono, Vaccinex, Tesaro, and IBM for work performed outside of the current study. Monika Joshi has acted as a paid consultant for Sanofi and received research funding from AstraZeneca and Pfizer for work performed outside of the current study. Michael B. Atkins has acted as a paid consultant for Bristol-Myers Squibb; has acted as a paid consultant and member of the advisory board for Novartis and Merck; has acted as a paid consultant for Genentech/Roche, Pfizer, Exelixis, Eisai, and Alexion; and has acted as a paid member of the advisory board for X4 Pharma and Arrowhead for work performed outside of the current study. Earle Burgess has received honoraria and speaking fees from and acted as a paid consultant/member of the advisory board for Roche, Exelixis, and Janssen; acted as a paid consultant/member of the advisory board for Takeda; and received research funding from Astellas and Pfizer for work performed outside of the current study. Theodore F. Logan has received research funding to his institution from Abbott Laboratories, Abraxis BioScience, Acceleron Pharma Inc, Amgen, Argos, AstraZeneca, Aveo, BioVex, Bristol-Myers Squibb, Eisai, Lilly, GlaxoSmithKline, Roche, Immatics, Merck, Novartis, Pfizer, Synta, Threshold Pharmaceuticals, Millennium, Tracon, Cerulean, EMD Serono, MacroGenics Peloton, Iovance Biotherapeutics, MedImmune, and Dynavax and has received research funding to his institution and acted as a paid member of the advisory board for Prometheus Laboratories for work performed outside of the current study. Xiaosha Xiang and Chad Glasser are employed by Acceleron Pharma Inc. Matthew L. Sherman is employed by and owns equity in Acceleron Pharma Inc. Elizabeth R. Plimack has received research funding from and acted as a paid consultant for Merck, Novartis, Genentech/Roche, AstraZeneca, and Bristol-Myers Squibb; has received research funding from and acted as a member of the Data Safety Monitoring Board for Pfizer and Eli Lilly; and has acted as a paid consultant for Acceleron Pharma Inc, Clovis, Exelixis, Horizon Pharma, Incyte, Inovio, and Janssen for work performed outside of the current study. The other authors made no disclosures.
Publisher Copyright:
© 2019 American Cancer Society
PY - 2019/7/15
Y1 - 2019/7/15
N2 - Background: In a prior open-label study, the combination of dalantercept, a novel antiangiogenic targeting activin receptor-like kinase 1 (ALK1), plus axitinib was deemed safe and tolerable with a promising efficacy signal in patients with advanced renal cell carcinoma (RCC). Methods: In the current phase 2, randomized, double-blind, placebo-controlled study, patients with clear cell RCC previously treated with 1 prior angiogenesis inhibitor were randomized 1:1 to receive axitinib plus dalantercept versus axitinib plus placebo. Randomization was stratified by the type of prior therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS in patients with ≥2 prior lines of anticancer therapy, overall survival, and the objective response rate. Results: Between June 10, 2014, and February 23, 2017, a total of 124 patients were randomly assigned to receive axitinib plus dalantercept (59 patients) or placebo (65 patients). The median PFS was not found to be significantly different between the treatment groups (median, 6.8 months vs 5.6 months; hazard ratio, 1.11 [95% CI, 0.71-1.73; P =.670]). Neither group reached the median overall survival (hazard ratio, 1.39 [95% CI, 0.70-2.77; P =.349]). The objective response rate was 19.0% (11 of 58 patients; 95% CI, 9.9%-31.4%) in the dalantercept plus axitinib group and 24.6% (15 of 61 patients; 95% CI, 14.5%-37.3%) in the placebo plus axitinib group. At least 1 treatment-emergent adverse event of ≥grade 3 was observed in 59% of patients (34 of 58 patients) in the dalantercept group and 64% of patients (39 of 61 patients) in the placebo group. One treatment-related death occurred in the placebo plus axitinib group. Conclusions: Although well tolerated, the addition of dalantercept to axitinib did not appear to improve treatment-related outcomes in previously treated patients with advanced RCC.
AB - Background: In a prior open-label study, the combination of dalantercept, a novel antiangiogenic targeting activin receptor-like kinase 1 (ALK1), plus axitinib was deemed safe and tolerable with a promising efficacy signal in patients with advanced renal cell carcinoma (RCC). Methods: In the current phase 2, randomized, double-blind, placebo-controlled study, patients with clear cell RCC previously treated with 1 prior angiogenesis inhibitor were randomized 1:1 to receive axitinib plus dalantercept versus axitinib plus placebo. Randomization was stratified by the type of prior therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS in patients with ≥2 prior lines of anticancer therapy, overall survival, and the objective response rate. Results: Between June 10, 2014, and February 23, 2017, a total of 124 patients were randomly assigned to receive axitinib plus dalantercept (59 patients) or placebo (65 patients). The median PFS was not found to be significantly different between the treatment groups (median, 6.8 months vs 5.6 months; hazard ratio, 1.11 [95% CI, 0.71-1.73; P =.670]). Neither group reached the median overall survival (hazard ratio, 1.39 [95% CI, 0.70-2.77; P =.349]). The objective response rate was 19.0% (11 of 58 patients; 95% CI, 9.9%-31.4%) in the dalantercept plus axitinib group and 24.6% (15 of 61 patients; 95% CI, 14.5%-37.3%) in the placebo plus axitinib group. At least 1 treatment-emergent adverse event of ≥grade 3 was observed in 59% of patients (34 of 58 patients) in the dalantercept group and 64% of patients (39 of 61 patients) in the placebo group. One treatment-related death occurred in the placebo plus axitinib group. Conclusions: Although well tolerated, the addition of dalantercept to axitinib did not appear to improve treatment-related outcomes in previously treated patients with advanced RCC.
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U2 - 10.1002/cncr.32061
DO - 10.1002/cncr.32061
M3 - Article
C2 - 30951193
AN - SCOPUS:85063896581
SN - 0008-543X
VL - 125
SP - 2400
EP - 2408
JO - Cancer
JF - Cancer
IS - 14
ER -