Pfizer speeds ahead with bispecific development

On Monday Pfizer revealed plans for a pivotal trial of PF-08634404, the anti-PD-1 x VEGF bispecific it licensed from 3SBio for $1.25bn, in extensive stage SCLC, and the phase 2/3 study is already posted on clinicaltrials.gov and expected to start imminently.

Pfizer’s trial follows in the footsteps of BioNTech’s pumitamig, which began its phase 3 Rosetta-Lung01 study in this indication earlier this year. It will evaluate PF-08634404 in combination with chemotherapy, beginning with an open-label phase 2 cohort and progressing to a phase 3 head to head against Tecentriq plus chemo, with overall survival as the primary endpoint.

In Roche’s Impower-133 trial, Tecentiq plus chemo yielded a 12.3-month median overall survival benefit, and this is one bar that PF-08634404 will need to surpass.

For its part, BioNTech at this year’s World Congress on Lung Cancer reported global phase 2 data that supported the initiation of its own phase 3 study. Pumitamig demonstrated an ORR of 76% among 38 first-line ES-SCLC patients, and a median PFS of 6.8 months.

At the dose selected for phase 3, 20mg/kg, the ORR increased to 85%, but median PFS was slightly lower at 6.3 months. Even so, in a cross-trial comparison these results exceeded the 60% ORR and 5.2 months of mPFS achieved by Tecentriq plus chemo in Impower-133.

Ivonescimab

Akeso, meanwhile, is targeting a different SCLC population for its Summit-partnered anti-PD-1 x VEGF bispecific ivonescimab: the company recently launched the Harmoni-9 trial in China, evaluating ivonescimab in limited-stage SCLC. Akeso first mooted plans for an ES-SCLC study in 2022, but no updates have emerged since.

Beyond SCLC, Pfizer has also revealed its intention to start phase 1/2 trials of PF-08634404 in liver, urothelial and renal cancers, as well as a phase 1/2 study evaluating combinations with ADCs in NSCLC.

Anti-PD-(L)1 x VEGF bispecific pivotal trials in SCLC

Source: OncologyPipeline.