AstraZeneca’s Imfinzi can’t have it all.
While the PD-L1 inhibitor posted a clinical win in muscle-invasive bladder cancer (MIBC), it also chalked up a failure in early-stage non-small cell lung cancer (NSCLC).
First, adding Imfinzi to chemotherapy before surgery—followed by Imfinzi monotherapy—significantly prolonged the lives of patients with MIBC compared with presurgical chemo alone, AZ said Tuesday.
Besides meeting statistical significance on that secondary endpoint of overall survival, the phase 3 NIAGARA trial also hit its primary goal of event-free survival. On that metric, the trial showed that the Imfinzi regimen significantly reduced the risk of cancer disease recurrence or death.
What’s more, the addition of Imfinzi didn’t cause more patients to discontinue treatment because of adverse events, nor did it compromise patients’ ability to undergo surgery, AZ said.
AZ said it will share the full data with regulators. As Thomas Powles, M.D, an investigator in the NIAGARA, noted in a statement, about half of patients with MIBC still experience disease recurrence or progression after receiving the current standard of care.
The NIAGARA win puts Imfinzi on a potential collision course with Merck & Co.’s PD-1 inhibitor Keytruda, which in October recorded a disease-free survival win from the phase 3 Ambassador trial when used only after surgery in MIBC. The Keytruda study has yet to report its overall survival data.
In addition, Bristol Myers Squibb’s Opdivo also boasts FDA approval for the adjuvant treatment of bladder cancer at high risk of recurrence after radical resection. The CheckMate-274 trial supporting that 2021 approval remains ongoing as overall survival data, while favoring Opdivo, have yet to reach statistical significance.
Compared with Keytruda and Opdivo’s postsurgical adjuvant approach, Imfinzi’s continuous neoadjuvant-plus-adjuvant treatment method uses the immunotherapy both before and after surgery. The FDA isn’t the biggest fan of that perioperative design because it doesn’t tease out the contribution of each treatment phase. But AZ has the statistically significant life extension showing to back its case, while neither of the rival adjuvant therapies can say the same.
As for the failed study, Imfinzi didn’t significantly improve the risk of disease recurrence or death versus placebo when used after complete tumor resection in stage 1b to 3a NSCLC that expresses PD-L1 on at least 25% of tumor cells. The result came from a global phase 3 trial coded ADJUVANT BR.31, which was sponsored by the Canadian Cancer Trials Group.
The flop came as a disappointment given that Merck’s Keytruda and Roche’s PD-L1 inhibitor Tecentriq each carry FDA approvals as adjuvant treatments for early-stage NSCLC in broader populations covering patients whose tumors have even lower PD-L1 expression.
It’s not common for drugmakers to announce results from outside clinical studies, especially when they are negative. AZ bucked that trend with its announcement about the Imfinzi lung cancer fail on Tuesday.
Meanwhile, AZ has its own AEGEAN trial, which like NIAGARA adopted a perioperative design. The study tested Imfinzi continuously pre- and post-surgery in early-stage NSCLC. The study met its primary endpoint of event-free survival, showing Imfinzi pared down the risk of disease recurrence or death by 32% in stage 2 to 3b NSCLC. Overall survival data remained immature at the time of the readout.
AZ filed the AEGEAN data with the FDA last year, and the company’s April investor update listed a potential decision as a first-half event this year. Even if approved, perioperative Imfinzi would have a hard time challenging Keytruda, which has secured a first-in-class nod backed by an overall survival win.
Besides AEGEAN, AZ is also testing Imfinzi as monotherapy or in combinations in several early-stage NSCLC trials dubbed PACIFIC-4, 5, 8 and 9.