ASCO26: Ivonescimab improves survival in NSCLC

Akeso and Summit Therapeutics' PD-1xVEGF bispecific antibody ivonescimab has significantly improved overall survival in the HARMONi-6 trial, reinforcing a previously reported benefit in progression-free survival.

HARMONi-6 is comparing ivonescimab to BeOne Medicines' PD-1 inhibitor Tevimbra (tislelizumab), both in combination with chemotherapy, as a first-line treatment for squamous non-small cell lung cancer (NSCLC) in a Chinese patient population.

The data revealed at ASCO showed median OS was 27.9 months in the ivonescimab group, versus 23.7 months with Tevimbra, equivalent to a 34% improvement, with a side effect profile that was "comparable" between the two groups, according to Dr Shun Lu of the Shanghai Chest Hospital in China.

It's an important finding, given that a PD-1/PD-L1 inhibitor plus chemo is the standard first-line approach for NSCLC, and showing an OS advantage is viewed as being key to changing clinical practice. ASCO commentator Dr David Spiegel of the Sarah Cannon Research Institute in the US, said the results are impressive, but cautioned that it is still too early to gauge the significance of the results beyond a population in China.

"It's hard to know how this applies to a population of patients beyond there," he said, as there may be differences in ethnicity that affect how drugs like this work. "These results are certainly very encouraging," he added, whilst pointing out that international studies – including the ongoing HARMONi-3 – should answer the ethnicity question.

That study – which is comparing ivonescimab to MSD's PD-1 inhibitor Keytruda (pembrolizumab) in a similar setting and is due to report next year – will be watched closely by oncologists as well as other companies developing PD-1 and VEGF targeted drugs.

MSD, Pfizer, and BioNTech/Bristol Myers Squibb have spent billions of dollars acquiring assets since ivonescimab first outperformed Keytruda in the HARMONi-2 trial in previously untreated, PD-L1-positive NSCLC, generating keen interest in adding the anti-VEGF component to standard immunotherapy.

At this year's ASCO, BMS and BioNTech have reported updated results from the phase 2/3 ROSETTA-Lung02 study of their pumitamig candidate with chemo in previously-untreated NSCLC, revealing a confirmed objective response rate (ORR) of 57.1% in non-squamous disease and 68.4% in patients with squamous tumours, and an overall disease control rate (DCR) of 100%.

Meanwhile, phase 2 dose-ranging results with Pfizer's PFE-08634404 (SSGJ-707), as a monotherapy in patients with advanced NSCLC with a PD-L1 biomarker score of 1% or less, revealed a 75% ORR in patients with squamous tumours and 63.6% in the non-squamous group. Pfizer licenses the drug from China's 3SBio.

Another mid-stage study of PFE-08634404, in treatment-naïve endometrial cancer patients, revealed an ORR of up to 86%.

Ivonescimab is already under review by the FDA in combination with chemo for patients with EGFR-mutated, based on the HARMONi trial, with an action date of 14th November. It is already on the market for this indication in China.