Pfizer targets VEGF bispecific white space

Pfizer has so far followed in the footsteps of its PD-(L)1 x VEGF rivals with pivotal trials of its contender, PF-08634404, but now it’s taking a more unusual step. A new Pfizer-sponsored phase 3, Symbiotic-Gyn-18, will be run in first-line endometrial cancer, according to a recent listing on clinicaltrials.gov.The lead PD-(L)1 x VEGF players, Akeso/Summit and Bristol Myers Squibb/BioNTech, haven’t ventured into this tumour type. Pfizer hasn’t released any data yet on PF-08634404 in endometrial cancer, although phase 2 results in this setting are due to be presented in an ASCO poster.This could give an indication of how PF-08634404 might perform in Symbiotic-Gyn-18. The trial, not slated to start until October, will compare PF-08634404 plus chemo followed by PF-08634404 maintenance, versus Keytruda plus chemo followed by Keytruda maintenance, in patients with first-line mismatch repair-proficient (pMMR) stage III and IV endometrial cancer. The primary endpoint is progression-free survival.Keytruda plus chemo was US approved in June 2024 for first-line endometrial cancer, irrespective of MMR status, backed by the NCI-sponsored Keynote-868 study. In pMMR patients the combo produced a median PFS of 13.1 months versus 8.7 months for chemo alone – equating to a 46% reduction in the risk of disease progression or death.GSK’s Jemperli, alongside chemo, got an all-comers label a couple of months later; it had previously had the go-ahead only in MMR-deficient disease.Others gunning for first-line pMMR endometrial cancer include AstraZeneca, with Enhertu, and Merck & Co, with the TROP2-targeting ADC sacituzumab tirumotecan.No plans?Meanwhile, Akeso/Summit and Bristol/BioNTech haven’t disclosed any phase 3 plans for their contenders, ivonescimab and pumitamig respectively, in endometrial cancer. However, endometrial patients were included in an early readout from a Chinese phase 1/2 solid tumour trial of pumitamig sponsored by that asset’s originator, Biotheus.Elsewhere, Pfizer also intends to take PF-08634404 into a phase 3 trial in first-line bladder cancer, testing a combination with its Astellas-partnered Nectin-4-targeting ADC Padcev. Again, no plans for ivonescimab or pumitamig pivotal trials have been mentioned for this use.Pfizer licensed PF-08634404, then coded SSGJ-707, from China’s 3SBio for $1.25bn up front in May 2025. Other big pharmas in PD-(L)1 x VEGF include Merck & Co, which paid LaNova $588m up front for MK-2010, and AbbVie, which earlier this year licensed RemeGen’s RC148. Pfizer-sponsored pivotal trials of PF-08634404TrialSettingRegimenPrimary endpointNoteSymbiotic-Lung-011st-line squam & non-squam NSCLC+ chemo, vs Keytruda + chemoPFS & OSStarted Jan 2026, completes Feb 2029Symbiotic-Lung-04*1st-line ES-SCLC+ chemo, vs Tecentriq + chemoOS**Started Dec 2025, completes Jun 2030Symbiotic-GI-031st-line colorectal cancer+ chemo, vs Avastin + chemoPFS & OSStarted Dec 2025, completes Mar 2030C6461016*1st-line gastroesophageal cancer+ chemo, vs Opdivo + chemoPFS & OS**Started Apr 2026, completes Jul 2031Symbiotic-Gyn-181st-line pMMR endometrial cancer+ chemo, vs Keytruda + chemoPFSTo start Oct 2026 & complete Jun 2029Unnamed1st-line bladder cancer+ Padcev, control undisclosedUndisclosedPfizer has disclosed plans here, but no trial listed yetNotes: *phase 2/3, others are phase 3; **phase 3 part; pMMR=mismatch repair proficient. Source: OncologyPipeline & clinicaltrials.gov.