JAVELIN Renal 101: a randomized, phase 3 study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC)

Date 21 October 2018
Event ESMO 2018 Congress
Session Presidential Symposium 2
Topics Renal Cell Cancer
Anticancer Agents
Immunotherapy
Presenter Robert Motzer
Authors R.J. Motzer1, K. Penkov2, J.B.A.G. Haanen3, B.I. Rini4, L. Albiges5, M.T. Campbell6, C.K. Kollmannsberger7, S. Negrier8, M. Uemura9, J.L. Lee10, H. Gurney11, R. Berger12, M. Schmidinger13, J. Larkin14, M.B. Atkins15, J. Wang16, P.B. Robbins17, A. Chudnovsky18, A. Di Pietro19, T.K. Choueiri20
  • 1Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Medical Oncology, Private Medical Institution "Euromedservice", St. Petersburg/RU
  • 3Division Of Medical Oncology, The Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
  • 4Medical Oncology, Cleveland Clinic, 44195 - Cleveland/US
  • 5Department Of Cancer Medicine, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 6Department Of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 7Medical Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 8D'oncologie Médicale, Centre Léon Bérard, 69008 - Lyon/FR
  • 9Medical Oncology, Osaka University Hospital, Osaka/JP
  • 10Department Of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul/KR
  • 11Medicine And Health Sciences, Macquarie University, 2109 - Macquarie Park/AU
  • 12Institute Of Onocology And Radiotherapy, Chaim Sheba Medical Center, 52621 - Ramat Gan/IL
  • 13Department Of Medicine I, Clinical Division Of Oncology And Comprehensive Cancer Center, Medical University of Vienna, 1090 - Vienna/AT
  • 14Department Of Medical Oncology, Royal Marsden NHS Foundation Trust, London/GB
  • 15Oncology & Medicine, Georgetown-Lombardi Comprehensive Cancer Center, 20007 - Washington DC/US
  • 16Oncology, Pfizer, Cambridge/US
  • 17Translational Oncology, Pfizer, San Diego/US
  • 18Immuno-oncology, Pfizer, Cambridge/US
  • 19Immuno-oncology, Pfizer, Milan/IT
  • 20Medical Oncology, The Lank Center for Genitourinary Oncology Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston/US

Abstract

Background

In a phase 1b trial, 1L A + Ax had encouraging antitumor activity for patients (pts) with aRCC (Lancet Oncol. 2018;19:451).

Methods

Eligible pts with clear-cell aRCC, ECOG ≤ 1, and no prior systemic therapy were randomized 1:1 (stratified by ECOG and geographic region) to receive A 10 mg/kg IV Q2W + Ax 5 mg PO BID in 6-wk cycles or S 50 mg PO QD on schedule 4/2; all prognostic risk groups were included. Primary endpoints were progression-free survival (PFS; by blinded independent central review [BICR] per RECIST v1.1) and overall survival (OS) in pts with PD-L1+ tumors (≥ 1% of immune cells). Secondary endpoints included PFS by BICR and OS irrespective of PD-L1 expression, objective response (OR), and safety.

Results

As of 20 Jun 2018, 886 pts were randomized (A + Ax: N = 442; S: N = 444); of these, 21%/62%/16% had favorable/intermediate/poor IMDC risk criteria (not reported in < 1%). In 560 pts (63.2%) with PD-L1+ tumors, median PFS was 13.8 vs 7.2 mo in A + Ax vs S arms, respectively (HR = 0.61; p < .0001; Table). Median PFS in pts irrespective of PD-L1 expression was 13.8 vs 8.4 mo (HR = 0.69; p = .0001). PFS and OR results favored A + Ax in pts irrespective of PD-L1 expression and in all MSKCC/IMDC prognostic risk groups. OS data were immature at data cutoff (< 16% of pts with events). In A + Ax vs S arms, grade ≥3 treatment-emergent adverse events occurred in 71.2% vs 71.5% of pts and led to discontinuation of any study drug in 22.8% vs 13.4%; deaths due to study treatment toxicity occurred in 0.7% vs 0.2% of pts.

Pts with PD-L1+ tumors

A + Ax (N = 270)

S (N = 290)

PFS per BICR (primary endpoint)

Median (95% CI), mo

Stratified hazard ratio (95% CI); 1-sided p value

13.8 (11.1, not estimable)

7.2 (5.7, 9.7)

0.61 (0.475, 0.790); p < .0001

Confirmed objective response rate per BICR

Objective response rate (95% CI), %

Stratified odds ratio (95% CI); 1-sided p value

55.2 (49.0, 61.2)

25.5 (20.6, 30.9)

3.732 (2.532, 5.371); p < .0001

Pts irrespective of PD-L1 expression

A + Ax (N = 442)

S (N = 444)

PFS per BICR

Median (95% CI), mo

Stratified hazard ratio (95% CI); 1-sided p value

13.8 (11.1, not estimable)

8.4 (6.9, 11.1)

0.69 (0.563, 0.840); p = .0001

Confirmed objective response rate per BICR

Objective response rate (95% CI), %

Stratified odds ratio (95% CI); 1-sided p value

51.4 (46.6, 56.1)

25.7 (21.7, 30.0)

3.098 (2.300, 4.148); p < .0001

Conclusions

This randomized phase 3 trial met its primary objective of significantly improving PFS in pts with PD-L1+ aRCC treated with A + Ax vs S. PFS and OR benefit was also observed in pts irrespective of PD-L1 expression and across all prognostic risk groups. The safety profiles were consistent with those of prior studies of each drug. These results support A + Ax as a potential new 1L standard-of-care for pts with aRCC.

Clinical trial identification

Clinical Trial Number: NCT02684006

Editorial Acknowledgement

Medical writing support was provided by ClinicalThinking Inc., Hamilton, NJ, USA.