AstraZeneca has dosed the first patient in the Phase III PACIFIC-9 clinical trial of durvalumab plus monalizumab or its oleclumab in unresectable, Stage III non-small cell lung cancer (NSCLC) patients.

An immune checkpoint inhibitor, monalizumab acts on the NKG2A receptors expressed on tumour infiltrating cytotoxic CD8+ T cells and NK cells. 

Through a joint-development and marketing agreement with Innate Pharma, AstraZeneca gained complete oncology rights to monalizumab in October 2018.

Sponsored by AstraZeneca, the randomised, double-blind, multicentre international trial will analyse the safety and efficacy of durvalumab alone or along with oleclumab or monalizumab+ in trial subjects.

The NSCLC patients should not have advanced after receiving definitive platinum-based concurrent chemoradiation therapy (CRT). 

The trial intends to detect whether adding monalizumab or oleclumab to standard-of-care durvalumab can boost outcomes for NSCLC patients in this setting. 

It is anticipated to enrol NSCLC patients across over 200 centres.

With the dosing of the first subject in this trial, Innate is entitled to receive a milestone payment worth $50m from AstraZeneca.

According to the interim analysis data from the randomised Phase II COAST trial, monalizumab plus durvalumab boosted objective response rate (ORR) and extended progression-free survival (PFS) versus durvalumab alone in NSCLC patients.

AstraZeneca Oncology R&D executive vice-president Susan Galbraith said: “Durvalumab has transformed the treatment of patients with unresectable, Stage III NSCLC, and we’re excited by the promise of extending its benefit through novel combinations with two potential first-in-class monoclonal antibodies demonstrating strong clinical activity. 

“Based on the stand-out results from COAST, we are pleased that the Phase III trial is underway, which we hope will bring new treatment options to patients and further increase the potential for long-term survival benefit in this setting.”

In October 2018, the companies signed an agreement to enhance their respective oncology portfolio.