Abstract 719P
Background
In a phase 1b/2 trial (NCT02501096), LEN (a multikinase inhibitor of VEGFR 1−3 and FGFR 1–4) + PEMBRO (a PD-1 antibody) had promising efficacy in advanced RCC in both immune checkpoint blockade (ICB)-naïve and ICB-refractory patients (pts). We present an exploratory serum biomarker analysis for LEN + PEMBRO in ICB-naïve pts with advanced RCC.
Methods
Pts received LEN 20 mg PO daily + PEMBRO 200 mg IV every 3 weeks. Tumors were assessed by investigators per immune-related RECIST. 38 Serum biomarkers were quantified (at baseline, cycle 1 day 15 [C1D15], and C2D1) using custom multi-analyte profile immunoassay panels, SIMOA assays, and ELISA. Baseline biomarker levels were correlated with objective response (OR; complete response + partial response) via the Wilcoxon rank sum test, and progression-free survival (PFS) via univariate Cox regression analysis. Associations between composite biomarker scores (CBSs; including biomarkers identified by analyses with LEN + everolimus) and PFS were made.
Results
Biomarkers were analyzed in 27 ICB-naïve pts treated with LEN + PEMBRO. Treatment increased levels of 13 biomarkers (eg, CXCL9, CXCL10, VEGF, IFN-γ, FGF-23, and VEGF-D) and decreased levels of 5 biomarkers (eg, ANG-2 and VEGFR-2) at both C1D15 and C2D1. ORs occurred in 70.4% of pts and were associated with high baseline levels of VEGFR-2 and low baseline levels of VDBP, TNFR2, FGF-21, IL-2RA, CRP, vWF, and IL-18BP (P<0.05). Longer PFS was associated with low baseline levels of 5 biomarkers (table). CBS data will be presented.
Conclusions
In this exploratory analysis, low baseline levels of FGF-21, IL-2RA, IL-18BP, and TNFR2 were associated with OR and longer PFS in pts with advanced RCC treated with LEN + PEMBRO. Conclusions are limited due to testing of multiple variables in a small sample. The efficacy and safety of LEN + PEMBRO in pts with advanced RCC is being further evaluated in a phase 3 study (NCT02811861). Table: 719P
| Marker | Cutoff value | n (high group) | Median PFS (high group), months | n (low group) | Median PFS (low group), months | P-value | P-value with false discovery rate | Hazard ratio (95% CI) |
| FGF-21 | 0.4 ng/mL | 8 | 9.6 | 19 | 22.4 | 0.001 | 0.02 | 5.13 (1.76–14.98) |
| IL-2RA | 3.4 ng/mL | 7 | 7.6 | 20 | 22.4 | 0.001 | 0.02 | 5.02 (1.74–14.50) |
| IL-18BP | 18 ng/mL | 7 | 9.7 | 20 | 22.4 | 0.008 | 0.08 | 3.75 (1.32–10.66) |
| IL-10 | 2.4 pg/mL | 9 | 9.7 | 18 | 25.1 | 0.01 | 0.08 | 3.61 (1.28–10.13) |
| TNFR2 | 15 ng/mL | 7 | 11.7 | 20 | 19.2 | 0.04 | 0.3 | 2.83 (1.02–7.84) |
Clinical trial identification
NCT02501096.
Editorial acknowledgement
Medical writing support was provided by Oxford PharmaGenesis, Newtown, PA and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
C-H. Lee: Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Calithera; Research grant/Funding (institution): Lilly. Y. Adachi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eisai Co., Ltd. H. Ikezawa: Full/Part-time employment: Eisai Co., Ltd. S.D. Li: Full/Part-time employment: Eisai Inc. Y. Funahashi: Full/Part-time employment: Eisai Co., Ltd. Y. Minoshima: Full/Part-time employment: Eisai Co., Ltd. P. Kubiak: Full/Part-time employment: Eisai Inc. R. Perini: Full/Part-time employment: Merck & Co., Inc. M. Ren: Full/Part-time employment: Eisai Inc. A.D. Smith: Full/Part-time employment: Eisai Ltd. R.J. Motzer: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Merck; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Bristol-Myers Squibb.