4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).

Background

mSCPC is an orphan disease with a poor prognosis. First line systemic treatment relies on platinum-based polychemotherapies (PBPC). These combinations remain poorly effective with median progression-free survival (PFS) and overall survival (OS) around 7.5 months and 16 months respectively [Pagliaro 2010; Nicholson 2013]. SCPC is a disease with a virally induced oncogenesis, moreover PD-L1 is commonly expressed with an expression rate of 62.2% in primary tumours and a strong correlation between PD-L1 in the primary tumour and metastases [Udager 2016]. Immunotherapies targeting the PD-1/PD-L1 axis are effective in other squamous cell or HPV related cancers. There is no consensus on a second line systemic treatment in mSCPC. Tumour mass is assumed to be reduced as a result of the first line chemotherapy. PBPC are known to be able to trigger immunogenic cell death. The maintenance strategy after systemic chemotherapy which has controlled the disease is a validated concept in many tumour models. Maintenance treatment with immunotherapy after initial PBPC may help to maintain disease control in mSCPC setting.

Trial design

PULSE trial is a prospective multicenter open label phase II study that will enroll 32 patients. Patients with unresectable locally advanced or metastatic SCPC must have carried out a radiological assessment showing a non-progressive disease after 3 to 6 cycles of a first line PBPC. Patients previously treated by an immunotherapy are excluded. A minimal period of 3 weeks washout after chemotherapy is required before starting intravenous maintenance Avelumab. It will be administered every two weeks at the dose of 10mg/kg until progression or unacceptable toxicity. The primary objective is to assess PFS according to RECIST 1.1 criteria. Secondary objectives are overall survival, impact of PL-L1 expression, safety, quality of life. Exploratory endpoints include blood immune-response monitoring, correlation of tumour immune infiltrate and PD-L1 expression on PFS. Screening across ∼15 sites in France is being conducted with first site initiated in February 2019.

Clinical trial identification

NCT03774901.

Editorial acknowledgement

Legal entity responsible for the study

Thiery-Vuillemin.

Funding

Pfizer.

Disclosure

N. Gassian: Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Novartis Pharma SAS; Travel / Accommodation / Expenses: Pfizer. G. Mouillet: Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Merck Serono; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Janssen Cilag; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Astellas Pharma; Travel / Accommodation / Expenses: Pfizer. F. Calcagno: Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Bayer HealthCare SAS; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Sanofi. A. Thiery-Vuillemin: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/ Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Astellas Pharma. All other authors have declared no conflicts of interest.