Pfizer Accelerates PF-08634404 Bispecific Development with Multiple Phase 3 Trials Following $1.25B 3SBio Deal
核心洞察
Pfizer has launched multiple pivotal trials for PF-08634404 (搜索), an anti-PD-1 (搜索) x VEGF (搜索) bispecific acquired from 3SBio (搜索) for $1.25 billion, targeting extensive-stage small cell lung cancer (搜索) and first-line non-small cell lung cancer (搜索).
The company is directly competing with BioNTech's pumitamig (搜索) and Akeso (搜索)'s ivonescimab in the same indications, with all three bispecifics being tested against current standard-of-care treatments including Keytruda plus chemotherapy.
Phase 3 studies will evaluate PF-08634404 (搜索) combinations in colorectal cancer (搜索) against Avastin plus chemotherapy, with trials expected to begin in December 2025 and March 2026.
Pfizer is rapidly advancing its newly acquired anti-PD-1 (搜索) x VEGF (搜索) bispecific PF-08634404 (搜索) into multiple phase 3 trials across several cancer indications, marking an aggressive push into the competitive bispecific antibody market following its $1.25 billion licensing deal with China's 3SBio (搜索) in May 2024.
Extensive-Stage Small Cell Lung Cancer Trial Launches
The pharmaceutical giant has revealed plans for a pivotal phase 2/3 trial of PF-08634404 (搜索) in extensive-stage small cell lung cancer (搜索) (ES-SCLC), with the study already posted on clinicaltrials.gov and expected to start imminently. The trial will evaluate PF-08634404 in combination with chemotherapy, beginning with an open-label phase 2 cohort before progressing to a phase 3 head-to-head comparison against Roche's Tecentriq plus chemotherapy, with overall survival as the primary endpoint.
This approach directly follows BioNTech's strategy with pumitamig (搜索), which began its phase 3 Rosetta-Lung01 study in the same indication earlier this year. The competitive bar is set by Roche's Impower-133 trial, where Tecentriq plus chemotherapy yielded a 12.3-month median overall survival benefit.
BioNTech's global phase 2 data, reported at this year's World Congress on Lung Cancer, demonstrated promising results that supported initiation of its phase 3 study. Pumitamig (搜索) achieved a 76% objective response rate (ORR) among 38 first-line ES-SCLC patients, with a median progression-free survival (PFS) of 6.8 months. At the dose selected for phase 3 development (20mg/kg), the ORR increased to 85%, though median PFS was slightly lower at 6.3 months. These results exceeded the 60% ORR and 5.2 months median PFS achieved by Tecentriq plus chemotherapy in Impower-133.
Comprehensive NSCLC Development Program
Pfizer has also initiated a fully-fledged phase 3 trial in first-line non-small cell lung cancer (搜索) (NSCLC), combining PF-08634404 (搜索) with chemotherapy against Keytruda plus chemotherapy. The study mirrors approaches taken by competitors, with Akeso (搜索)'s ivonescimab being tested in the Harmoni-3 trial and BioNTech's pumitamig (搜索) in Rosetta Lung-02.
The company is strategically splitting its NSCLC trial by histology into squamous and non-squamous cohorts, an approach also undertaken in BioNTech's Rosetta Lung-02 trial. Akeso (搜索)'s Harmoni-3 trial was recently upsized with co-primary endpoints split between squamous and non-squamous histologies, with readouts expected in H2 2026 for squamous and H1 2027 for non-squamous populations.
Colorectal Cancer Expansion
Colorectal cancer (搜索) represents an increasingly popular target for PD-(L)1 x VEGF (搜索) bispecifics, with Pfizer joining the competitive landscape. The company's phase 3 colorectal study is scheduled to begin in December 2025, testing PF-08634404 (搜索) plus chemotherapy against Avastin plus chemotherapy in microsatellite stable patients without BRAF V600E mutations.
This positions Pfizer directly against Akeso (搜索), which launched the Chinese phase 3 Harmoni-GI6 study in May following impressive results where ivonescimab combined with anti-CD47 (搜索) antibody ligufalimab and chemotherapy yielded an 88% response rate in front-line disease. BioNTech's pumitamig (搜索) colorectal trial is set to start in March 2026, creating a three-way competition in this indication.
Broader Development Pipeline
Beyond these pivotal studies, Pfizer has revealed intentions to initiate phase 1/2 trials of PF-08634404 (搜索) in liver, urothelial, and renal cancers, as well as a phase 1/2 study evaluating combinations with antibody-drug conjugates in NSCLC. Meanwhile, Akeso (搜索) is targeting a different SCLC population with ivonescimab in limited-stage disease through its recently launched Harmoni-9 trial in China.
Strategic Positioning
The $1.25 billion upfront payment to 3SBio (搜索) for PF-08634404 (搜索) (originally coded SSGJ-707) represented a significant investment in the PD-(L)1 x VEGF (搜索) bispecific space. Early data revealed in an ASCO poster showed impressive activity, though questions about toxicity were raised. 3SBio has also initiated its own Chinese phase 3 trial in front-line NSCLC, notably different from Pfizer's approach as it involves head-to-head monotherapy comparison versus Keytruda in PD-L1 (搜索) expressing patients only.
The rapid advancement of multiple phase 3 programs demonstrates Pfizer's commitment to establishing a strong position in the competitive bispecific market, where it faces established players with advanced development timelines.