Pfizer has thrust into the global race for a best-in-class bispecific antibody that inhibits both programmed cell death protein 1/ligand 1 (PD-1/L1) and vascular endothelial growth factor (VEGF) as it searches for a checkpoint inhibitor-based immunotherapy to combine with its own vedotin-based antibody-drug conjugates (ADCs).
Key Takeaways
- Pfizer is paying $1.25bn upfront and up to $4.8bn in milestones for global ex-China rights to 3SBio's PD-1 x VEGF bispecific antibody SSGJ-707.
- The US major plans to study its vedotin-based antibody-drug conjugates in combination with the bispecific, adding to immuno-oncology combo programs underway with other partners including Summit/Akeso and Merck & Co.
- These most recently include the Phase III BE6A LUNG-02 trial studying Pfizer's sigvotatug vedotin, an integrin beta-6-targeting ADC, with Keytruda for first-line, PD-L1-high NSCLC.
That quest came to fruition on 19 May as the US major announced a deal for exclusive global (ex-mainland China) development, manufacturing and commercialization rights to 3SBio’s PD-1 x VEGF bispecific antibody SSGJ-707, for which it is paying $1.25bn upfront.
Development, regulatory and sales milestones of up to $4.8bn, plus double-digit tiered royalties on net sales, are also part of the transaction, under which Pfizer gains an option to commercialization rights in China, where the bispecific is Phase III-ready.
The US firm will in addition take a $100m equity stake in 3SBio and plans to manufacture the drug substance at an existing US site in Sanford, NC and the finished product at its McPherson, KS facility.
3SBio noted in its 2024 annual results presentation that SSGJ-707 was designed using the Chinese company’s proprietary bispecific antibody platform CLF2 (common light chain Linear-Fabs IgG). Compared with Summit Therapeutics and Chinese partner Akeso’s PD-1 x VEGF bispecific antibody ivonescimab, preclinical data showed SSGJ-707 had “stronger inhibitory effects on VEGF-induced angiogenesis,” 3SBio stated.
In the presence of VEGF, the bispecific also demonstrated enhanced binding affinity for PD-1 and stronger internalization by T-cells, followed by translocation to lysosomes and VEGF depletion, it added.
SSGJ-707 has already received regulatory clearance in China to progress to a head-to-head Phase III trial as a monotherapy versus Merck & Co.’s PD-1-targeting blockbuster Keytruda (pembrolizumab) in Chinese patients with previously untreated, PD-L1-positive non-small cell lung cancer (NSCLC).
Full data from an interim analysis of a Phase II trial assessing SSGJ-707 as a monotherapy in previously untreated, PD-L1-positive NSCLC will be released during the upcoming American Society of Clinical Oncology (ASCO) annual meeting, to be held in Chicago 30 May-3 June. In January, a preliminary readout from the study showed arguable superiority over ivonescimab in terms of objective response rate and disease control rate, with the caveat of the difficulty of cross-trial comparisons.
The bispecific is also being studied in multiple China-only Phase II studies as a monotherapy or in combination with chemotherapy for first-line use in NSCLC, as well as for metastatic colorectal cancer and advanced gynecological tumors. In the US, an investigational new drug application has been approved for a Phase I trial in advanced solid tumors.
Summit Partnership Unaffected
Pfizer’s tie-up with 3SBio came on the heels of a clinical trial collaboration forged in February with Summit, in which the US major is evaluating ivonescimab in combination with several of its own vedotin-based ADCs in solid tumors, beginning in the middle of this year.
Bernstein analysts said in a 19 May research note they had been told by Pfizer that it did not anticipate any changes to the clinical collaboration agreement with Summit as a result of the new transaction with 3SBio. While Pfizer/Summit have not specified the specific ADCs they intend to jointly study in combination with ivonescimab, Pfizer had disclosed previously it was eyeing a front-line combo with its PD-L1-targeting ADC PF-08046054 (PDL1V).
To date, Pfizer has been studying PDL1V in a Phase I trial both as monotherapy and in combination with Keytruda in solid tumors. While positive results encouraged the firm to decide in February to advance the ADC into two Phase III programs in NSCLC and head and neck squamous cell cancer in the second half of this year, details are lacking as to whether these trials will investigate any combination involving Keytruda.
Pfizer’s Keytruda Combo Alliances
Pfizer and Astellas Pharma are already partnering with Merck & Co. for the approved combination of Padcev (enfortumab vedotin), a Nectin-4-targeting ADC, with Keytruda for first-line, previously untreated urothelial cancer. The Padcev/Keytruda combo is also being evaluated in two other Phase III programs in muscle-invasive bladder cancer, both sponsored by Merck.
The two US giants are also co-developing a combination of disitamab vedotin, a HER2-targeting ADC originally developed by China’s RemeGen, and Keytruda in the Phase III DV-001 trial for certain urothelial cancers in the first-line setting. Both Padcev and disitamab vedotin’s Keytruda combination efforts resulted from Merck’s prior partnerships with Seagen, which Pfizer acquired in 2023.
This May, Pfizer initiated the Phase III BE6A LUNG-02 trial to study sigvotatug vedotin, an integrin beta-6-directed ADC, in combination with Keytruda for first-line treatment of PD-L1 high NSCLC, according to Citeline’s Trialtrove.
