A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma

Martin H. Voss, Rupal S. Bhatt, Nicholas J. Vogelzang, Mayer Fishman, Robert S. Alter, Brian I. Rini, J. Thaddeus Beck, Monika Joshi, Ralph Hauke, Michael B. Atkins, Earle Burgess, Theodore F. Logan, David Shaffer, Rahul Parikh, Nauman Moazzam, Xiaosha Zhang, Chad Glasser, Matthew L. Sherman, Elizabeth R. Plimack

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2400-2408
Number of pages9
JournalCancer
Volume125
Issue number14
DOIs
StatePublished - Jul 15 2019

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Renal Cell Carcinoma
Placebos
Disease-Free Survival
axitinib
Human ALK1-Fc fusion protein
Activin Receptors
Therapeutics
Angiogenesis Inhibitors
Survival
Random Allocation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Voss, M. H., Bhatt, R. S., Vogelzang, N. J., Fishman, M., Alter, R. S., Rini, B. I., ... Plimack, E. R. (2019). A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma. Cancer, 125(14), 2400-2408. https://doi.org/10.1002/cncr.32061
Voss, Martin H. ; Bhatt, Rupal S. ; Vogelzang, Nicholas J. ; Fishman, Mayer ; Alter, Robert S. ; Rini, Brian I. ; Beck, J. Thaddeus ; Joshi, Monika ; Hauke, Ralph ; Atkins, Michael B. ; Burgess, Earle ; Logan, Theodore F. ; Shaffer, David ; Parikh, Rahul ; Moazzam, Nauman ; Zhang, Xiaosha ; Glasser, Chad ; Sherman, Matthew L. ; Plimack, Elizabeth R. / A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma. In: Cancer. 2019 ; Vol. 125, No. 14. pp. 2400-2408.
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title = "A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma",
abstract = "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.",
author = "Voss, {Martin H.} and Bhatt, {Rupal S.} and Vogelzang, {Nicholas J.} and Mayer Fishman and Alter, {Robert S.} and Rini, {Brian I.} and Beck, {J. Thaddeus} and Monika Joshi and Ralph Hauke and Atkins, {Michael B.} and Earle Burgess and Logan, {Theodore F.} and David Shaffer and Rahul Parikh and Nauman Moazzam and Xiaosha Zhang and Chad Glasser and Sherman, {Matthew L.} and Plimack, {Elizabeth R.}",
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Voss, MH, Bhatt, RS, Vogelzang, NJ, Fishman, M, Alter, RS, Rini, BI, Beck, JT, Joshi, M, Hauke, R, Atkins, MB, Burgess, E, Logan, TF, Shaffer, D, Parikh, R, Moazzam, N, Zhang, X, Glasser, C, Sherman, ML & Plimack, ER 2019, 'A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma', Cancer, vol. 125, no. 14, pp. 2400-2408. https://doi.org/10.1002/cncr.32061

A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma. / Voss, Martin H.; Bhatt, Rupal S.; Vogelzang, Nicholas J.; Fishman, Mayer; Alter, Robert S.; Rini, Brian I.; Beck, J. Thaddeus; Joshi, Monika; Hauke, Ralph; Atkins, Michael B.; Burgess, Earle; Logan, Theodore F.; Shaffer, David; Parikh, Rahul; Moazzam, Nauman; Zhang, Xiaosha; Glasser, Chad; Sherman, Matthew L.; Plimack, Elizabeth R.

In: Cancer, Vol. 125, No. 14, 15.07.2019, p. 2400-2408.

Research output: Contribution to journalArticle

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.

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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