2026 ESMO: 3SBio Reports Long-Term Follow-up of Tivunatamig Plus Chemo in First-Line Advanced NSCLC China Phase II

Competition in first-line PD-1/VEGF bispecific antibodies for advanced NSCLC has entered the phase of long-term data. For the class benchmark ivonescimab, a Phase 1b study reported median PFS of 11.4 months in all patients, NR in PD-L1-positive patients and 7.2 months in negative patients ; an updated analysis showed mPFS of 15.2 months with a 12-month PFS rate of 56.3%, but grade ≥3 TRAEs of 58.3% . Against this backdrop, 3SBio's tivunatamig (PF-08634404/SSGJ-707) carries the weight of being a flagship China out-licensing deal: in 2025, 3SBio granted Pfizer global development and commercialization rights for $1.4 billion upfront, $100 million equity investment, and a potential total of over $6 billion, a record upfront for a China innovative drug license-out. Pfizer has moved fast, with 11 registered international trials across more than 1,700 sites; the registry shows a Phase 3 study (NCT06980272) with pembrolizumab as active control, 420 planned participants, primary endpoint of IRRC-assessed PFS, started June 2025 ; and a Phase 1/2 combination study (NCT07227298) testing PF-08634404 with ADC partners such as Sigvotatug Vedotin, planning 162 participants（需要核查）.

The ESMO 2026 presentation reported long-term follow-up from a China Phase 2 study (data cutoff August 6, 2026): 261 patients total, 139 squamous and 122 non-squamous; 50% aged over 65, 80% with smoking history, over 40% with TPS<1%. At the selected 10 mg/kg Q3W dose with carboplatin plus paclitaxel, cORR was 80.7% in squamous disease (control 67.7%) and 77.5% in non-squamous (control 44.7%); median PFS was 13.6 vs 8.3 months in squamous, and 13.8 vs 9.7 months in non-squamous. Per the article, while cross-trial comparison is not valid, this mPFS is the longest among PD-1/VEGF bispecifics in Phase 2. A differentiating highlight is the ctDNA translational analysis: among 126 patients with detectable baseline ctDNA and paired sampling, 61.9% achieved ctDNA clearance at C3D1 (about 9 weeks); cleared patients had mPFS of 16.4 months vs 9.6 months for non-clearers, suggesting a possible early biomarker of benefit. On safety, grade ≥3 TRAE rates were broadly comparable to the tislelizumab control arm, with no new grade 5 treatment-related events since the SITC disclosure.

The significance is that the efficacy first disclosed at SITC last year has been consolidated: with the cutoff extended from February to August, ORR rose markedly and PFS further improved, showing a 'longer follow-up, more durable benefit' pattern — a key positive signal supporting Phase 3 confirmation for a Phase 2 study. Compared with disclosed ivonescimab data , tivunatamig pairs leading mPFS with a manageable safety profile, plus rare-in-class evidence linking early ctDNA clearance to PFS, leaving room for differentiated global Phase 3 designs such as NCT06980272 .

Not yet disclosed: overall survival data, PFS hazard ratios and confidence intervals, subgroup results (e.g., TPS<1%), and details of the Phase 2 control regimen remain to be confirmed. The next key milestones are readouts from the multiple global Phase 3 studies, which will determine the commercial height of this bispecific and provide an important reference for the entire PD-1/VEGF class (needs verification).