Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial

Ulka Vaishampayan, Patrick Schöffski, Alain Ravaud, Christian Borel, Julio Peguero, Jorge Chaves, John C Morris, Nuria Kotecki, Martin Smakal, Dongli Zhou, Silke Guenther, Marcis Bajars, James L Gulley, Ulka Vaishampayan, Patrick Schöffski, Alain Ravaud, Christian Borel, Julio Peguero, Jorge Chaves, John C Morris, Nuria Kotecki, Martin Smakal, Dongli Zhou, Silke Guenther, Marcis Bajars, James L Gulley

Abstract

Background: Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti-PD-L1) monotherapy in patients with mRCC as either first-line (1 L) or second-line (2 L) treatment.

Methods: Patients with mRCC with a clear-cell component who were treatment naive (1 L subgroup) or had disease progression after one prior line of therapy (2 L subgroup) received avelumab 10 mg/kg intravenous infusion every 2 weeks. Endpoints included confirmed best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), PD-L1 expression, and safety.

Results: A total of 62 patients were enrolled in the 1 L subgroup, and 20 patients were enrolled in the 2 L subgroup. In the 1 L and 2 L subgroups, confirmed objective response rates were 16.1 and 10.0%, median DOR was 9.9 months (95% confidence interval [CI], 2.8-not evaluable) and not evaluable (95% CI, 6.9-not evaluable), median PFS was 8.3 months (95% CI, 5.5-9.5) and 5.6 months (95% CI, 2.3-9.6), and median OS was not evaluable (95% CI, not evaluable) and 16.9 months (95% CI, 8.3-not evaluable), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 51 patients in the 1 L subgroup (82.3%) and 14 patients in the 2 L subgroup (70.0%). Grade ≥ 3 TRAEs occurred in eight patients in the 1 L subgroup (12.9%) and one patient in the 2 L subgroup (5.0%). No treatment-related deaths occurred.

Conclusion: Avelumab showed clinical activity and a manageable safety profile in both the 1 L and 2 L treatment setting in patients with mRCC. These data support the use of avelumab in combination with other agents in mRCC.

Trial registration: ClinicalTrials.gov: NCT01772004 ; registered 21 January, 2013.

Keywords: Avelumab; Metastatic; PD-L1; Phase I; Renal cell carcinoma.

Conflict of interest statement

UV reports research funding from Novartis, Exelixis, and Pfizer; consultancy remuneration from Bayer, Exelixis, Pfizer, Bristol-Myers Squibb, and EMD Serono; and honoraria from Sanofi, Pfizer, Bristol-Myers Squibb, Bayer, and Exelixis. PS reports consultancy or advisory remuneration from Blueprint Medicines, Eisai, Ellipses Pharma, Eli Lilly, Loxo Oncology, Deciphera Pharmaceuticals, Merck KGaA, Servier, Genmab, Adaptimmune, Intellisphere, Transgene, and Plexxikon, and research funding from Blueprint Medicines, Boehringer Ingelheim, CoBioRes NV, Eisai, Exelixis, G1 Therapeutics, Eli Lilly, Novartis, PharmaMar, and Plexxikon. AR reports honoraria and travel expenses from Bristol-Myers Squibb, Novartis, Ipsen, Astra Zeneca, and Pfizer; and consultancy or advisory remuneration from Bristol-Myers Squibb, Ipsen, Novartis, Pfizer, Astra Zeneca, and Roche. JCM reports speakers bureau services for Boehringer Ingelheim and Merck KGaA; travel expenses from Amgen, Eisai, Merck KGaA, and VentiRx Pharmaceuticals; and other relationship with Merck KGaA. MS reports research funding from Merrimack. DZ reports employment with and research funding from Merck KGaA. SG and MB report employment with Merck KGaA. JLG reports research funding from Astellas and Medivation, Bavarian Nordic, Merck KGaA, NantBioScience, and Pfizer. All remaining authors have declared no competing interests.

Figures

Fig. 1
Fig. 1
Time to and duration of confirmed response. 1 L first-line, 2 L second-line
Fig. 2
Fig. 2
Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). a PFS in the first-line (1 L) subgroup. b PFS in the second-line (2 L) subgroup. c OS in the 1 L subgroup. d OS in the 2 L subgroup. CI confidence interval, NE not evaluable

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Source: PubMed

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