AstraZeneca touts Imfinzi immunotherapy combos for lung cancer in push to drive PD-L1 drug uptake
Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.
Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an Innate’s anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.
At a median 11.5-month check-in, the combination of Imfinzi and oleclumab cut the risk of disease progression or death by 56% compared with Imfinzi alone, and the Imfinzi-monalizumab combo hit a 35% risk reduction. The 10-month PFS was 64.8% and 72.7% for Imfinzi-oleclumab and Imfinzi-monalizumab, respectively, compared with 39.2% for solo Imfinzi.
Meanwhile, Imfinzi-oleclumab posted an ORR of 30% while Imfinzi-monalizumab posted a 36% ORR. Imfinzi alone hit 18%.
On the safety side, AstraZeneca said it didn’t see any new safety red flags with the combinations, with a 39.4% rate of Grade 3 side effects on Imfinzi, 40.7% for Imfinzi-oleclumab and 27.9% for Imfinzi-monalizumab. The most common Grade 3/4 side effect reported was dyspnea, and one Grade 3/4 case of pneumonitis was reported in the Imfinzi-monalizumab arm.
AstraZeneca sees these combinations as a potential additional crack at Stage III NSCLC, where one in four patients are diagnosed and Imfinzi has established itself as standard care in the unresectable subpopulation. The British drugmaker is planning a registration trial for the combinations.
Imfinzi is one of seven PD-(L)1 drugs currently on the market and hasn’t exactly taken the world by storm quite like its far more successful competitors Keytruda from Merck and Bristol Myers Squibb’s Opdivo. But AstraZeneca does see potential for the blockbuster drug, which is racking up indications and posted a big breakthrough early this month.
Last week, AstraZeneca announced a combination of Imfinzi and the long-gestating CTLA-4 antibody tremelimumab posted a 28% improvement in PFS and a 23% improvement in overall survival compared with chemo alone in patients Stage IV NSCLC, according to data from the Phase III POSEIDON study.
The results could pitch Imfinzi-tremelimumab as a natural challenger to Bristol Myers’ blockbuster Opdivo-Yervoy combo, but the skepticism over the CTLA-4 arm of both combinations is still potent. Yervoy has long been under scrutiny over whether it adds much to that regimen given the solo strength of Opdivo, and the case for tremelimumab is even more tenuous after the drug took so long to cycle through clinical development.
Either way, these combination studies look to breathe new life into Imfinzi as it continues challenging the big dogs in this space.