A Pilot Study to Assess Changes in Tumor Biology Following Second-line Treatment With Pembrolizumab Plus Lenvatinib in Patients With Advanced Pancreatic Ductal Adenocarcinoma

Description

Primary Efficacy Objective

Corresponding Endpoint To obtain a preliminary estimate of the ORR* of the combination of pembrolizumab and lenvatinib in patients with advanced pancreatic ductal adenocarcinoma ORR, defined by the proportion of participants who have a CR or PR as determined by RECIST version

Secondary Objective

Corresponding Endpoints

• Determine progression free survival (PFS) according to RECIST version 1.1 and iRECIST.

PFS defined as the time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first

* To estimate DOR according to RECIST v1.1 and iRECIST.
* DOR defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first
* To estimate DCR using RECIST 1.1 and with confirmatory assessment as required by iRECIST at any time during the trial.
* DCR defined as the proportion of subjects who have a CR, PR, or SD
* To evaluate the efficacy, toxicity and survival following treatment with pembrolizumab and lenvatinib • OS defined as the time from the date of enrollment to the date of death due to any cause.
* Occurrence and severity of AEs, with severity determined according to NCI CTCAE,

Exploratory Objective

Corresponding Endpoints To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may be indicative of clinical response/resistance, safety, pharmacodynamic activity, and/or the mechanism of action of pembrolizumab and lenvatinib Molecular (genomic, metabolic and/or proteomic) determinants of response or resistance to treatments, using blood and/or tumor tissue

* Change in T-cell composition of tumor as identified by multiplex immunofluorescent assay of serial biopsies obtained from patients. Tumor infiltrate will be assessed for any change in response to this therapeutic approach.
* Additional measurements will include changes in immune composition of tumor stroma, T-cell receptor composition in infiltrating T cells, and serum cytokines. Tumor infiltrate and circulating cytokines will be assessed for change in response to these therapies.