Despite mixed results, analysts maintained faith in ivonescimab’s ability to cross over between Eastern and Western patient populations.
Summit Therapeutics’ PD-1xVEGF bispecific antibody ivonescimab hit the co-primary endpoint of progression-free survival in a Phase III trial Friday, providing the first evidence that global pivotal trials of the asset can reproduce the impressive efficacy shown in China. However, ivonescimab missed on overall survival, raising questions about its approvability in the U.S.
Analysts at Truist Securities were nevertheless optimistic about the results. “This is good,” they wrote in a note to investors Friday morning, “and the East vs West populations looks similar enough for us to remain optimistic that the data generated for ivonescimab in China will be reproducible in Western populations.”
Wall Street appeared to not be as certain, as Summit’s shares fell 15% to $22.25 in premarket trading.
Summit’s Chinese partner Akeso has found ivonescimab improves progression-free survival (PFS) compared to Keytruda as a first-line therapy in non-small cell lung cancer (NSCLC) patients in China. Although the interim overall analysis fell short of statistical significance, ivonescimab was cleared last month by China’s National Medical Products Administration for the first-line treatment of certain patients with NSCLC. Truist analysts see Summit’s data in EGFR-mutant NSCLC, where PFS and overall survival (OS) were similar across geographies, as evidence the company can replicate the Chinese results in global trials.
Summit and Akeso triggered a surge in interest in the mechanism last year when they linked the bispecific to a 49% drop in the risk of disease progression or death compared to Merck’s Keytruda. Since then, BioNTech has acquired its PD-L1xVEGF partner for $800 million, Merck has paid $588 million for an asset and Pfizer has handed over $1.25 billion to join the race.
The companies have bet big on PD-1/L1xVEGF bispecifics despite outstanding questions about whether global trials can replicate Chinese data and the effect of the therapies on overall survival. Summit’s first global Phase III readout on ivonescimab is a step toward answering these questions.
Despite the mixed results, Summit still plans to file for FDA approval of ivonescimab but noted that it would have to “consider the timing of the filing.” The agency has said that a statistically significant overall survival benefit is necessary to support approval, but as Summit stated in its Friday announcement, “There are no current FDA-approved regimens that have demonstrated a statistically significant overall survival benefit in this patient setting.”
The HARMONi trial enrolled people with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who had progressed on a third-generation tyrosine kinase inhibitor such as AstraZeneca’s Tagrisso. Checkpoint inhibitors including Keytruda have struggled in EGFR-mutant NSCLC, potentially because PD-L1 expression is lower than in some other tumor types.
Participants in the trial received ivonescimab or placebo on top of platinum-doublet chemotherapy. Around 38% of patients were enrolled in Western countries. At the prespecified primary data analysis, Summit and Akeso found their bispecific reduced the risk of disease progression or death by 48% compared to placebo. The trial linked ivonescimab to a significant improvement in progression-free survival (PFS), a co-primary endpoint.
The overall survival (OS) data favored ivonescimab but fell short of statistical significance, missing the other co-primary endpoint. Even so, Truist analysts said that they think the data “will be ample” to seek approval in the indication in the U.S. and European Union and position Summit to start building out its commercial organization ahead of potential launches in larger indications.
First-line NSCLC is one of the big opportunities for ivonescimab. Summit is running two Phase III trials to compare its bispecific to Keytruda in first-line NSCLC, with one study enrolling patients with high PD-L1 expression and the other trial accepting participants with any level of PD-L1 expression.
