Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance — PIONeeR  

Non-small Cell Lung Cancer Clinical Trial

Official title: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR Clinical Study)

Status Active, not recruiting

Clinical Trial Summary

Research Hypothesis Lung cancer is the leading cause of cancer-related mortality in France and in western countries, accounting for more than 1.8 million new cases and 1.5 million deaths worldwide in 2012. Recent advances in the management of patients with Non-small Cell Lung Cancer Patients (NSCLC) include the use of therapies targeting oncogenes but a molecular alteration is currently found in only the half of the non-squamous NSCLC . More recently, immune check point inhibitors (ICI), firstly targeting PD-(L)1, became available and demonstrate an overall survival advantage over standard second-line chemotherapy both in squamous and non-squamous NSCLC. Unfortunately, this global overall survival benefit is driven by approximately 20% of the patient's population while a large majority of patients is in fact progressing in the first weeks of treatment.

In the context of personalized medicine, innovative immunotherapy strategies in oncology are based on the principle of immune-contexture and require:

• The identification of biomarkers for assessing the specific immune-contexture of each patient (microenvironment, tumors and effector cells)

• The development of new treatments targeting their appropriate effector cells in monotherapy or combination treatments.

The current PIONEER-Clinical study is aimed at assessing how to overcome resistance to ICIs monotherapies or ICI in combination with platinum-based chemotherapies, with experimental precision immunotherapies combined to Durvalumab in 2nd, 3rd or 4th line, in advanced NSCLC progressors patients after up to 18more than 6 w. of anti PD (L) 1. for ICIs monotherapies and after more than 12w. of anti PD(L)1 in combination with chemotherapies.

Some supplementary blood and tissue samples are aimed at identification of personalized patients' biomarkers, correlation of them with the efficacy endpoints, in order to better understand mechanisms of resistance and improve their future treatment.

Clinical Trial Description

Study Design:

During a mandatory post treatment 28-day wash-out period, 135 advanced NSCLC patients with progressive disease evaluated between 6 and 18w. of a second or third line ICI monotherapy; will undergo a screening visit. After signing an informed written consent, if they are found eligible, their participation in the study will ensue.

Treatment allocation will be performed using the randomization module of the eCRF, :

• Arm A: combination of Durvalumab (MEDI4736) + Monalizumab (IPH2201), to target a PD-L1 co-inhibitory pathway

• Arm B: combination of Durvalumab + oleclumab (MEDI9447), to target limitations of antitumor T-cell immunity caused by adenosine receptor signaling (inclusions closed on May 10, 2021)

• Arm C: combination of Durvalumab + AZD6738, to potentially enhance anti- tumour T-cell responses

• Arm D: a standard third or forth-line chemotherapy maintenance (Docetaxel)

• Arm E : combination of Durvalumab + MET kinase inhibitor Savolitinib (AZD6094)

A maximum of 120 patients will be randomized, with 30 patients per arm (4 arms). ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

• NCT number: NCT03833440
• Study type: Interventional
• Source: Assistance Publique Hopitaux De Marseille
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 8, 2019
• Completion date: February 2025