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 Logan, David Shaffer, Rahul Parikh, Nauman Moazzam, Xiaosha Zhang, Chad Glasser, Matthew L. Sherman, Elizabeth R. Plimack

Research output: Contribution to journalArticle

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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)
JournalCancer
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

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

Keywords

  • angiogenesis
  • antiangiogenic agents
  • chemotherapy
  • drug therapy
  • randomized controlled trial
  • renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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; Shaffer, David; Parikh, Rahul; Moazzam, Nauman; Zhang, Xiaosha; Glasser, Chad; Sherman, Matthew L.; Plimack, Elizabeth R.

In: Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Voss, MH, Bhatt, RS, Vogelzang, NJ, Fishman, M, Alter, RS, Rini, BI, Beck, JT, Joshi, M, Hauke, R, Atkins, MB, Burgess, E, Logan, T, 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. 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 ; 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.
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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.",
keywords = "angiogenesis, antiangiogenic agents, chemotherapy, drug therapy, randomized controlled trial, renal cell carcinoma",
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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

AU - Shaffer, David

AU - Parikh, Rahul

AU - Moazzam, Nauman

AU - Zhang, Xiaosha

AU - Glasser, Chad

AU - Sherman, Matthew L.

AU - Plimack, Elizabeth R.

PY - 2019/1/1

Y1 - 2019/1/1

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.

KW - angiogenesis

KW - antiangiogenic agents

KW - chemotherapy

KW - drug therapy

KW - randomized controlled trial

KW - renal cell carcinoma

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