Immunotherapy and VEGF-targeting therapies improve mRCC outcomes; however, immune escape and/or resistance often develops so new agents and combinations are needed. Here, we prospectively explore novel efficacy endpoints and report updated data from IMmotion150 (NCT01984242), a Ph II trial of atezo (anti–PD-L1) with or without bev (anti-VEGF) vs sun (TKI) in 1L mRCC.
Treatment-naive mRCC patients (pts) were randomized to atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w, atezo 1200 mg IV q3w alone or sun 50 mg PO QD 4 wk on/2 wk off. PD-L1 expression was scored on tumor-infiltrating immune cells (IC; VENTANA SP142 IHC assay). Coprimary endpoints were independent review (IRF)–assessed PFS (RECIST v1.1) in ITT and PD-L1 + (≥ 1% IC) pts. Other endpoints included investigator (INV)-assessed PFS by RECIST v1.1 and immune-modified RECIST (imRECIST) and patient-reported outcomes (PROs).
After a median 25.7 mo of follow-up, results remained consistent with the primary analysis (median follow-up, 20.7 mo), showing clinically meaningful benefit in IRF- and INV-PFS with atezo + bev vs sun in PD-L1+ pts (RECIST v1.1; Table). The INV-PFS (imRECIST) HR for atezo + bev vs sun was 0.78 in ITT pts and 0.47 in PD-L1+ pts (Table). Safety of atezo + bev was consistent with the known safety profile of each agent alone; further follow-up showed no new safety signals. PROs will be presented.
Updated efficacy (RECIST v1.1) confirmed the encouraging activity of atezo + bev in PD-L1+ 1L RCC, with no new safety signals. Data per imRECIST, compared with RECIST v1.1, showed benefit of atezo + bev in PD-L1+ and ITT pts and may contribute to our understanding of the clinical activity of cancer immunotherapy in mRCC. The clinical benefit of atezo + bev vs sun will be further evaluated in the ongoing Ph III study IMmotion151 (NCT02420821).Table:
|ITT||PD-L1 Expression on ≥ 1% of IC (PD-L1+)|
|Sun||Atezo||Atezo + Bev||Sun||Atezo||Atezo + Bev|
|n = 101||n = 103||n = 101||n = 60||n = 54||n = 50|
|Median PFS (IRF, RECIST v1.1) (95% CI), mo||8.1||6.7||11.6||6.4||5.4||12.1|
|(5.7, 10.9)||(5.4, 13.6)||(8.4, 17.3)||(3.8, 8.7)||(3.0, 11.1)||(8.2, 22.9)|
|Stratified HR vs sunitinib (95% CI)||—||1.04||0.95||—||0.97||0.65|
|(0.73, 1.48)||(0.67, 1.34)||(0.61, 1.54)||(0.40, 1.05)|
|Median PFS (INV, RECIST v1.1) (95% CI), mo||7.8||5.5||11.0||6.8||5.5||11.1|
|(5.7, 9.8)||(3.0, 8.3)||(8.2, 13.5)||(5.4, 11.2)||(3.0, 10.9)||(8.1, 16.7)|
|Stratified HR vs sunitinib (95% CI)||—||1.13||0.88||—||0.96||0.60|
|(0.82, 1.55)||(0.64, 1.22)||(0.63, 1.46)||(0.38, 0.94)|
|Median PFS (INV, imRECISTa) (95%, CI), mo||9.9||8.5||17.3||8.4||10.9||21.9|
|(7.0, 14.1)||(7.9, 13.6)||(11.6, 24.9)||(5.8, 11.3)||(5.4, 14.0)||(11.1, 27.6)|
|Stratified HR vs sunitinib (95% CI)||—||1.05||0.78||—||0.87||0.47|
|(0.74, 1.49)||(0.55, 1.11)||(0.55, 1.39)||(0.29, 0.78)|
imRECIST criteria are based on RECIST v1.1 and include adaptations for response patterns observed with cancer immunotherapy (Mazieres et al. ASCO 2016). Data cutoff: April 2017
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd
F. Hoffmann-La Roche, Ltd
T. Powles: Tumor advisory boards for Pfizer, Novartis, Roche, BMS, GSK, Merck, AZ. Travel, honararia and housing support for meetings/presentations from Pfizer, Novartis, BMS, MSD, Roche and Astra Zeneca. Institutional grant support from Roche, Merck and Novartis. D.F. McDermott: Consultant: Kidney Cancer Research: BMS, Pfizer, Merck, Novartis, Eisai, Exelixis, Array BioPharm, Genentech BioOncology Research Support: Kidney Cancer Research: Prometheus. B. Rini: Consulting and research funding from Roche. R.J. Motzer: Consultant: Exelixis, Eisai, Pfizer, Novartis Research: Exelixis, Eisai, BMS, Pfizer, Novartis M.B. Atkins: Michael B. Atkins is a consultant for Roche, BMS, Merck and Pfizer. L. Fong: Research support from Abbvie, BMS, Merck, Janssen, Roche/Genentech. R.W. Joseph: Consults or performs advisory boards for Merck, BMS, Exelixis, Genoptix I perform clinical trials with Merck, Roche, X4P, Amgen, Incyte. S.K. Pal: Consulting: Genentech, Aveo, Eisai, Roche, Pfizer, Novartis, Exelixis, Ipsen Honoraria: Genentech. A. Ravaud: Member of GU tumor advisory boards for Pfizer, Novartis, Roche, BMS, GSK. Travel and housing support for meeting or speeches from Pfizer, Novartis, BMS, MSD, and Astra Zeneca. Institutional grant support from Pfizer and Novartis. S. Bracarda: Advisory Board Member for Pfizer, Novartis, BMS, Roche, Genentech, IPSEN, Eusa Pharma V. Grünwald: Advisory role and has received honoraria: Pfizer, Novartis, Bristol Myer Squibb, Ipsen, Eisai, Roche. Research support is given from Pfizer, Novartis, BMS and MSD Merck. M. Staehler: Consultant/Honoraria/Research: Pfizer, GlaxoSmithKline, Novartis, Bayer, Roche, Aveo, EUSAPharm, Astellas, Ipsen, Exelixis, Pelloton, EISAI. Honoraria: EUSAPharm, Astellas, Pelloton. Research: Roche/Genentech, Immatics, Wilex J. Qiu: Genentech/Roche employee and stockholder A. Thobhani: Employee of Roche Products Ltd. M. Huseni: Employee at Genentech including stock ownership. C. Schiff: Employment at Genentech including stock ownership. B. Escudier: Honorarium received from: BMS, Novartis, Pfizer, Ipsen, Roche, Bayer, Calithera, Acceleron, EUSA, Eisai. All other authors have declared no conflicts of interest.