Imfinzi Combined with Oleclumab or Monalizumab Significantly Improves Clinical Outcomes in Unresectable Stage III NSCLC

September 18, 2021 /BioValleyBIOON/ --AstraZeneca(AstraZeneca) recently at the 2021 European MedicalTumorannounced at the European Society for Medical Oncology (ESMO) Virtual CongressAnti-PD-L1 Therapy Imfinzi (durvalumab) for the Treatment of Lung CancerLarge-scale randomized Phase 2 COAST trialClinical Trialof the results. The data show:In patients with unresectable stage III non-small cell lung cancer (NSCLC) without disease progression following concurrent chemoradiotherapy (CRT), combination therapy with Imfinzi plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab improved progression-free survival (PFS) and objective response rate (ORR) compared with Imfinzi monotherapy.

After a median follow-up of 11.5 months, the interim analysis results showed:Compared with Imfinzi monotherapy, combination therapy with Imfinzi and oleclumab reduced the risk of disease progression or death by 56%.（HR=0.44；95%CI:0.26-0.75），Combination therapy with Imfinzi and monalizumab reduced the risk of disease progression or death by 35%(HR = 0.65; 95% CI: 0.49–0.85). The 10-month PFS rate was 39.2% in the Imfinzi monotherapy arm, while the 10-month PFS rate was 64.8% in the Imfinzi + oleclumab arm and 72.7% in the Imfinzi + monalizumab arm.The results also showed: confirmed at the primary endpointIn terms of objective response rate (ORR), compared with the Imfinzi treatment group, the Imfinzi + oleclumab treatment group demonstrated a higher rate (30% vs 18%), and the Imfinzi + monalizumab treatment group also showed a higher rate (36% vs 18%).

In this study, the safety profiles across treatment groups were similar, with no new safety signals identified for any Imfinzi combination regimen. The incidence of grade ≥3 treatment-emergent adverse events (TEAEs; all causes) during the treatment period was 39.4% in the Imfinzi group, 40.7% in the Imfinzi + oleclumab group, and 27.9% in the Imfinzi + monalizumab group. The most common grade 3/4 TEAE was dyspnea (reported in 3.0%, 1.7%, and 1.6% of patients, respectively). Only one case of grade 3/4 pneumonitis was reported (1.6%), occurring in a patient who received Imfinzi + monalizumab.

Lung cancer is the leading cause of cancer death, accounting for approximately one-fifth of all cancer deaths, with 80–85% of lung cancer patients diagnosed with non-small cell lung cancer (NSCLC). One-quarter of NSCLC patients are diagnosed at stage III, of whom the majority# TumorFor unresectable disease (not amenable to surgical resection), the treatment goal at this stage is curative. The previous standard of care was chemoradiotherapy (CRT) followed by active surveillance to monitor disease progression; however, the prognosis was suboptimal, and long-term survival rates remained low.

Based on the results of the Phase III PACIFIC clinical trial,Imfinzi has been approved in multiple countries and regions worldwide (including the United States, China, Japan, and Europe) for the treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following chemoradiotherapy (CRT). Imfinzi is the first new therapy available for these patients in decades. Treatment with Imfinzi following CRT has become the global standard of care for patients in this setting.Since its initial approval in February 2018, more than 80,000 patients worldwide have been treated with Imfinzi.

Chair of the COAST Steering Committee, Yale Cancer Center and Smilow Cancer Hospital# TumorRoy S. Herbst, M.D., Chief of Medical Oncology, stated: “Imfinzi is the established standard of care for patients with unresectable stage III NSCLC, but solutions are still needed for patients who currently do not benefit from existing therapies. The significant improvements observed following the addition of oleclumab or monalizumab to Imfinzi, along with a robust safety profile, indicate that these new combinations could further redefine outcomes for these patients.”

AstraZenecaTumorSusan Galbraith, Executive Vice President, Research & Development, said: “Imfinzi has transformed the treatment of patients with unresectable stage III NSCLC, and we are excited to expand its efficacy through novel combinations with two potential first-in-class monoclonal antibodies demonstrating robust clinical activity. Based on the compelling results from the COAST study, we plan to initiate registration trials with the aim of bringing these new treatment options to patients, thereby further enhancing the curative potential in this setting.”

Stage III (locally advanced) NSCLC is typically classified into three substages (IIIA, IIIB, IIIC), defined by the extent of local tumor spread and resectability. Stage III differs from Stage IV, in which the cancer has spread (metastasized) to distant organs, whereas treatment for most Stage III patients is currently pursued with curative intent. It is estimated that Stage III NSCLC accounts for approximately one-quarter of NSCLC incidence. The majority of Stage III NSCLC patients are diagnosed with unresectableTumor. Prior to the approval of Imfinzi, these patients had no new treatment options other than CRT for decades.

Imfinzi is a human monoclonal antibody that targets and binds to programmed death-ligand 1 (PD-L1), blocking the interaction between PD-L1 and PD-1 and CD80, to combatTumorimmune evasion strategy and relieve the inhibition of the immune response.

Based on the results of the Phase 3 PACIFIC study,Imfinzi is the first immunotherapy approved for curative-intent treatment following chemoradiotherapy (CRT) in patients with unresectable stage III non-small cell lung cancer (NSCLC), and has now become the global standard of care. Additionally, based on the results of the Phase 3 CASPIAN study, Imfinzi has also been approved in multiple countries worldwide for the treatment of extensive-stage small cell lung cancer (ES-SCLC).

Currently, AstraZeneca is conducting multiple registration trials focused on evaluating Imfinzi for the treatment of early-stage lung cancer, including in potentially curable settings (Phase III trials such as PACIFIC-2, -4, -5, MERMAID-1, -2, AEGEAN, ADJUVANT BR.31, ADRIATIC, etc.). Additionally, the company is conducting two Phase II platform trials to test novel combination therapies with Imfinzi in the unresectable stage III setting (COAST) and the neoadjuvant early-stage setting (NeoCOAST). (Bioon.com)

Original Source:Imfinzi combined with novel immunotherapies improved clinical outcomes for patients with unresectable, Stage III non-small cell lung cancer