André P. Fay, MD, PhD

Professor of Medicine - PUCRS School of MedicineChief, Medical Oncology Department at HSL – PUCRS/Grupo Oncoclínicas

Visiting Scientist at Dana-Farber/Harvard Medical School

Immunotherapy in Testicular Cancer: Were We Are and Perspectives

April, 4th, 2019

Introduction

• Testicular germ cell tumors are among the most chemo-sensitive solid

tumors

• A small proportion of patients fail to be cured with cisplatin-based

chemotherapy (3-4 cycles of BEP)

Indirect targeting of the tumor using the immune system

2013 2014

Cierna et al. Annals of Oncology 27: 300–305, 2016

Results

• PD-L1 expression:• 76% of seminomas

• 89% of non-seminomas

• The highest PD-L1 expression was found in choriocarcinomas, with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and the lowest expression in seminoma

• Dichotomized PD-L1 expression, only 20% of TGCTs had high PD-L1 expression (QS ≥ 10)

Cierna et al. Annals of Oncology 27: 300–305, 2016

PD-L1 expression is higher in patients with more advanced disease with poor prognostic features

Cierna et al. Annals of Oncology 27: 300–305, 2016

PFS according to PD-L1 expression

Cierna et al. Annals of Oncology 27: 300–305, 2016

Semaan, A et al. Immunotherapy: last bullet in platinum refractory germ cell testicular cancer. Future Oncology,2018

Semaan, A et al. Immunotherapy: last bullet in platinum refractory germ cell testicular cancer. Future Oncology,2018

Phase II trial of pembrolizumab in patients (pts) with incurable platinum refractory germ cell tumors (GCT)

Adra et al. J Clin Oncol 35, no. 15_suppl (May 20 2017) -NTC02499952

Results (N=12)

Adra et al. J Clin Oncol 35, no. 15_suppl (May 20 2017) -NTC02499952

Summary – Pembrolizumab in GCT

• Median # doses: 2 (1-8)• 6 grade 3 AEs• No partial or complete responses ORR=0%!• 2 patients had SD (radiologically) with rising AFP…

• (PD-L1 negative)

• 10 patients had PD• 2 patients with higher PD-L1 expression PD

Adra et al. J Clin Oncol 35, no. 15_suppl (May 20 2017) -NTC02499952

Cabozantinib + Nivolumab +Ipilimumab in GU Tumors

Nadal RM, et al. ASCO GU 2018: Abstr. 515.

Necchi et al. Eur Urol Focus (2018)

Seminoma Non-Seminoma

Necchi et al. Eur Urol Focus (2018)

Necchi et al. Eur Urol Focus (2018)

• Primary testicular lymphoma are rare extranodal large B-cell lymphomas. • Poor prognosis

• Frequent 9p24.1 copy number alterations associated increased expression of the programmed cell death protein 1 (PD-1) ligands PD-L1 and PD-L2.

• Activity of PD-1 blockade in other lymphomas with 9p24.1

1 complete response with Nivolumab

Ongoing Clinical Trials

Conclusion and Perspectives

• Germ cell tumors have excellent cure rates with standard treatment

• Small percentage of patients are refractory to several lines of chemotherapy

• Immunotherapy has not shown encouraging results so far, but may be a new hope

• Combinations with standard treatments?

• Biomarkers?

• TMB?

• MSI-High?

André P. Fay, MD, PhD

Andre.fay@pucrs.brAndre_Fay@dfci.harvard.edu

@DrAndreFay

Immunotherapy in Testicular Cancer: Were We Are and Perspectives