AstraZeneca’s PACIFIC-2 Phase III trial for Imfinzi (durvalumab) concurrently administered with chemoradiotherapy (CRT) did not achieve statistical significance for the primary endpoint of progression-free survival (PFS) versus CRT alone for the treatment of patients with unresectable, Stage III non-small cell lung cancer (NSCLC).
Imfinzi sequentially administered after platinum-based CRT is the established, global standard of care for the treatment of unresectable, Stage III NSCLC based on the results of the PACIFIC Phase III trial. The PACIFIC-2 trial was initiated to evaluate concurrent Imfinzi administration with CRT, with the aim of addressing patients who progress or discontinue treatment during CRT and are therefore ineligible for the PACIFIC regimen.
Initial analysis of the safety and tolerability for Imfinzi and CRT in this patient population showed that the profiles were broadly consistent with the known profiles of these treatments, although there was an increased rate of infection observed during the concurrent treatment period in the experimental arm.
Jeffrey D. Bradley, MD, Vice Chair of Proton Therapy & Technology Development, Penn Medicine, Philadelphia and principal investigator for the trial said:“While the PACIFIC-2 trial results did not show what we hoped, the PACIFIC regimen remains the standard of care for patients with unresectable, Stage III non-small cell lung cancer. As a community, we will take insights from these results to advance future research.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Our goal with the PACIFIC-2 trial was to address a remaining unmet need for patients in this setting by introducing immunotherapy even earlier and concurrently administering Imfinzi with chemoradiotherapy. While today’s results did not reach statistical significance, we will learn from this trial and we remain committed to improving patient outcomes by expanding the benefit of immunotherapy to lung cancer patients across treatment settings.”
AstraZeneca has several ongoing registrational trials focused on testing Imfinzi in early stages of lung cancer, including in resectable NSCLC (ADJUVANT BR.31), medically inoperable or unresected Stage I-II NSCLC (PACIFIC-4) and unresectable, Stage III NSCLC (PACIFIC-5, 8 and 9), and in limited-stage small-cell lung cancer (SCLC) (ADRIATIC).
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Stage III NSCLC
Each year, an estimated 2.2 million people are diagnosed with lung cancer globally.1 Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and SCLC, with 80-85% classified as NSCLC, making it the most common form of lung cancer.2-3 Approximately one in three patients with NSCLC are diagnosed at Stage III (locally advanced), where the majority of tumours are unresectable (cannot be removed with surgery).4-5
Stage III NSCLC is divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally.6 In contrast to Stage IV, when cancer has spread to other parts of the body (metastasised), the majority of Stage III patients are currently treated with curative intent.3,6
PACIFIC-2
The PACIFIC-2 trial was a Phase III, randomised, double-blind, placebo-controlled, multi-centre international study of Imfinzi concurrently administered with platinum-based CRT in patients with unresectable, Stage III NSCLC. In the trial, patients were randomised 2:1 to receive a 1,500mg fixed dose of Imfinzi or placebo every four weeks starting at the beginning of definitive CRT. Patients continued to receive Imfinzi or placebo as consolidation treatment after CRT until disease progression.
The trial was conducted at 88 centres across more than 20 countries involving 328 patients. The primary endpoint was PFS, and key secondary endpoints included overall survival, objective response rate and duration of response.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial results which have been confirmed in the real-world setting in the PACIFIC-R study.
Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial.
In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma in the US, EU, Japan and several other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively. Imfinzi is also approved in previously treated patients with advanced bladder cancer in a small number of countries.
Since the first approval in May 2017, more than 200,000 patients have been treated with Imfinzi.
As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal cancers and other solid tumours.
In 2023, AstraZeneca announced positive results for several Phase III trials evaluating Imfinzi in various combinations, including in ovarian (DUO-O) and endometrial (DUO-E) cancers with Lynparza (olaparib), gastric and gastroesophageal cancer (MATTERHORN) and resectable NSCLC (AEGEAN).
Source: AstraZeneca
