Poster Presentation COSA 2015 ASM

Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma (mRCC): association of biomarkers with clinical outcomes (#189)

Toni K Choueri 1 , Mayer N Fishman 2 , Bernard Escudier 3 , David F McDermott 4 , Harriet Kluger 5 , Walter M Stadler 6 , Jose L Perez-Gracia 7 , Douglas McNeel 8 , Brendan Curti 9 , Michael R Harrison 10 , Elizabeth R Plimack 11 , Leonard Appleman 12 , Lawrence Fong 13 , Charles G Drake 14 , Tina C Young 15 , Scott D Chasalow 15 , Petra Ross-Macdonald 15 , Jason S Simon 15 , Dana Walker 15 , Mario Sznol 5
  1. Dana-Farber Cancer Institute, Boston, MA, USA
  2. H. Lee Moffitt Cancer Centre & Research Institute, Tampa, FL, USA
  3. Institut Gustave Roussy, Villejuif, France
  4. Beth Israel Deaconess Medical Center, Boston, MA, USA
  5. Yale Cancer Center, New Haven, CT, USA
  6. Medicine, University of Chicago, Chicago, IL, USA
  7. University Clinic of Navarra , Pamplona, Spain
  8. Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
  9. Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA
  10. Duke University Medical Centre, Durham, NC, USA
  11. Fox Chase Cancer Centre, Philadelphia, PA, USA
  12. University of Pittsburgh Medical Center (UPMC) Cancer Pavilion, Pittsburgh, PA, USA
  13. University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
  14. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
  15. Bristol-Myers Squibb, Princeton, NJ, USA

Aims: This prospective biomarker study in patients with mRCC treated with programmed death-1 (PD-1) inhibitor nivolumab assessed baseline (BL) and changes in serum chemokines, tumor T cell infiltrates (TIL), gene expression, T cell repertoire (TCR), and other biomarkers potentially associated with clinical outcomes (NCT01358721).

Methods: Patients treated with 1–3 prior therapies received nivolumab 0.3, 2, or 10 mg/kg IV Q3W; treatment-naïve pts received 10 mg/kg IV Q3W. Biopsies were obtained at BL and cycle 2 day 8. Overall survival (OS) was estimated by Kaplan-Meier method. Tumor PD-L1 expression was measured by immunohistochemistry. PD-L1+ was defined as ≥5% tumor membrane staining; tumor burden response as ≥20% reduction. Gene expression was obtained on Affymetrix U219.

Results: 91 patients were treated. Of 56 evaluable BL biopsies, 32% were PD-L1+. Median OS (95% CI) was 16.4 mo (10.1–not reached [NR]) for 0.3 mg/kg, NR for 2 mg/kg, 25.2 mo (12.0–NR) for 10 mg/kg, and NR for treatment-naïve pts. 1-yr and 2-yr OS rates (95% CI) were 75% (64–83) and 58% (46–68), respectively. Median OS, mo (95% CI) in PD-L+ patient was not reached and 23.4 (13.1-33.3) in PD-L1- patients. Patients with tumor burden response (n = 13) had ≥ 1.3-fold differential BL expression of 311 genes (P < 0.01, false discovery rate < 16%). Cell-mediated immune transcripts were elevated.

Conclusions: Immune markers association at BL with subsequent tumor burden response suggests that infiltrating immune activating cells may mediate response to nivolumab in mRCC patients. Consistent with the randomized phase II study of nivolumab in mRCC, OS appears longer in PD-L1+ pts but promising in both PD-L1+ and PD-L1– patients, especially when treatment-naïve.

Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2015 ASCO Annual Meeting. All rights reserved.