Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and, in the US/Canada, advanced urothelial carcinoma progressed on platinum therapy. Here, we report phase 1b data from the multicohort JAVELIN Solid Tumor trial (NCT01772004) in pts with aRCC treated with avelumab monotherapy in either the 1L or 2L setting.
Eligible pts in the 1L subgroup had measurable aRCC with a clear cell component and ECOG ≤1; in the 2L subgroup, pts must have progressed after 1 prior line of therapy. All pts received avelumab 10 mg/kg IV Q2W until disease progression, unacceptable toxicity, or withdrawal. Assessments included objective response rate (ORR; according to RECIST v1.1 per investigator), progression-free survival (PFS), overall survival (OS), and safety.
As of 27 April 2017, 82 pts received avelumab: 62 pts as 1L (median follow-up, 14.2 mo [range, 6-17 mo]; 24 pts remained on treatment) and 20 pts as 2L (median follow-up, 22.1 mo [range, 16-23 mo]; 2 pts remained on treatment). Efficacy data are summarized below. The rates of treatment-related adverse events (TRAEs) were 75.8% (grade ≥3, 12.9%) and 70.0% (grade ≥3, 5.0%) in the 1L and 2L subgroups, respectively. The only grade ≥3 TRAE that occurred in > 1 pt was elevated lipase (n = 4); no TR deaths or unexpected immune-related TRAEs occurred. Updated data will be presented.Table: 877P
|1L (n = 62)||2L (n = 20)|
|Response ORR (95% CI), % Duration of response, median (95% CI), mo||16.1 (8.0-27.7) 10.4 (2.8-10.4)||10.0 (1.2-31.7) NE (6.9-NE)|
|PFS Median (95% CI), mo 6-mo rate (95% CI), %||8.3 (5.5-9.7) 55.7 (41.9-67.4)||5.6 (2.3-8.2) 44.9 (21.9-65.6)|
|OS Median (95% CI), mo 12-mo rate (95% CI), %||NE 85.9 (73.4-92.8)||16.9 (8.3-NE) 65.0 (40.3-81.5)|
NE, not estimable.
Avelumab, administered either as 1L or 2L monotherapy, showed durable responses, promising survival outcomes, and an acceptable safety profile in pts with aRCC. These data, as well as those recently reported from a phase 1b trial investigating the 1L combination of avelumab + axitinib (VEGF pathway inhibitor; NCT02493751), provide a rationale for the randomized, phase 3 JAVELIN Renal 101 trial (NCT02684006) comparing avelumab + axitinib with sunitinib as 1L treatment for pts with aRCC.
Clinical trial identification
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
This trial was sponsored by Merck KGaA, Darmstadt, Germany and is part of an alliance between Merck KGaA and Pfizer.
Medical writing support was provided by ClinicalThinking Inc., Hamilton, NJ, USA.
U.N. Vaishampayan: Consulting fees: Bayer, Exelixis, Novartis, Pfizer, BMS, Takeda; Research funding: Novartis, Exelixis, Pfizer; Honoraria: Sanofi, Pfizer, BMS, Bayer, Medivation, Takeda. P. Schöffski: Financial interests: Daiichi Sankyo, Eisai, Eli Lilly, Medpace, Novartis, Swedish Orphan Biovitrium, 6th Element Capital, Adaptimmune, Amcure, AstraZeneca, Bayer, Blueprint Medicines, BMS, Boehringer Ingelheim, Cristal Therapeutics, Epizyme, Genzyme, Ipsen, Loxo, Nektar, Novartis, Philogen, Piqur Therapeutics, Plexxikon, GSK, PharmaMar, Cobiores nv, Exelixis. C. Borel: Financial interest: Merck, BMS, AstraZeneca, Amgen. T. Song, J. Grewal: Financial interest: EMD Serono. S. Guenther: Financial interest: Merck KGaA. All other authors have declared no conflicts of interest.