A Multi-Cancer, Multi-State, Platform Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck to Correlate Clinical, Molecular and Immunologic Parameters With DNA Methylation — DOME  

Non-small Cell Lung Cancer Clinical Trial

Official title: A Multi-Cancer, Multi-State, Platform Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck to Correlate Clinical, Molecular and Immunologic Parameters With DNA Methylation (DOME)

Status Withdrawn

Clinical Trial Summary

This is a phase II, single center, open label, multi-cohort platform study to identify a signature in tumor tissues, blood or stool that might help identify participants who are more likely to experience tumor shrinkage or side effects from the combination of the study drugs durvalumab and oleclumab. In addition, this study will see if participants with certain types of advanced cancer benefit from the experimental drug combination of durvalumab and oleclumab, will evaluate the safety and tolerability of durvalumab and oleclumab, and to understand the effects that durvalumab and oleclumab have at a molecular level in tumor cells and their effects on the immune system. This study will look at subjects with locally advanced or recurrent/metastatic pancreatic ductal adenocarcinoma (PDAC), non-small-cell carcinoma (NSCLC) and squamous cell carcinoma of head and neck (SCCHN).

Within each cancer type, 40 patients will be enrolled (for a total of 120 patients on study):

20 patients will be enrolled with locally advanced disease ("window") and treated with durvalumab 1500 mg given by IV x 1 dose and oleclumab 3000 mg x 2 doses every 2 weeks prior to definitive therapy (e.g. surgery), and 20 patients will be enrolled with recurrent/metastatic ("metastatic") disease and treated with durvalumab 1500 mg given by IV every 4 weeks and oleclumab 3000 mg given by IV every 2 weeks x 4 doses then IV every 4 weeks till disease progression, toxicity, withdrawal of subject consent, or another discontinuation reason. For locally advanced PDAC patients, approximately 10 of the 20 subjects may receive 6-8 cycles of modified FOLFIRINOX (mFFX) prior to the administration of durvalumab and oleclumab.

Clinical Trial Description

The study hypothesis is that the combination of oleclumab (anti-cluster of differentiation [CD]73) with durvalumab (anti programmed cell death ligand 1 [PD-L1]) will demonstrate adequate safety, tolerability, and antitumor activity in subjects with locally advanced or recurrent/metastatic: pancreatic ductal adenocarcinoma (PDAC), non-small-cell lung cancer (NSCLC) and squamous cell carcinoma of head and neck (SCCHN), and that circulating free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) can yield cancer type-agnostic predictive biomarker(s) of response and/or toxicity in subjects receiving this combination. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Pancreatic Ductal Adenocarcinoma
• Squamous Cell Carcinoma of Head and Neck

• NCT number: NCT04262388
• Study type: Interventional
• Source: University Health Network, Toronto
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2021
• Completion date: January 2023