LM-299

BioNTech and partner Bristol Myers Squibb on Tuesday unveiled promising interim findings from a mid-stage study evaluating their investigational PD-L1xVEGF-A blocking bispecific antibody pumitamig (BNT327/BMS986545) in combination with chemotherapy to treat patients with locally advanced or metastatic triple-negative breast cancer (TNBC), irrespective of PD-L1 expression levels.After touting encouraging response data from an earlier Phase Ib/II trial in a treatment-naïve population at the San Antonio Breast Cancer Symposium (SABCS) last year, the partners — at this year’s meeting — reported further encouraging antitumour activity and a manageable safety profile for pumitamig across both first- and second-line treatment settings, laying the groundwork for the Phase III ROSETTA BREAST-01 trial.The Phase II study assessed two pumitamig regimens with chemotherapy: Cohort 1 received 15 or 20 mg/kg every two weeks with nab-paclitaxel, and Cohort 2 received a flat 20 mg/kg dose with either paclitaxel, gemcitabine plus carboplatin, or eribulin across three arms.Notable responsesThe interim analysis as of the October 1 cut-off included 74 patients with first- or second-line locally advanced/metastatic TNBC. Results showed that among 39 efficacy-evaluable patients in Cohort 1, the confirmed objective response rate (cORR) was 61.5%, whilst the unconfirmed ORR (uORR) was 71.8% and disease control rate was 92.3%. Additionally, responses proved consistent across PD-L1 expression levels, with an uORR of 70.6% observed in both combined positive score (CPS) ≥10 and CPS <10 subgroups.“The encouraging results are especially meaningful in patients with PD-L1 low or negative tumours…representing the potential of pumitamig…across PD-L1 expression levels, including patients who historically have had fewer effective treatments,” remarked Anne Kerber, head of development for haematology, oncology, cell therapy at BMS.The companies also noted higher pumitamig doses correlated with better responses, reaching 80.0% uORR at 20 mg/kg versus 63.2% at 15 mg/kg. In terms of lines of treatment, the uORRs were 76.5% and 68.2% in first- and second-line settings, respectively. Furthermore, the 9-month progression-free survival (PFS) rate was 59.3%, while median PFS, duration of response and overall survival were yet to mature at the time.Safety-wise, pumitamig’s profile was manageable, with Grade ≥3 treatment-related adverse events reported in 42.5% and 38.2% of patients in Cohorts 1 and 2, respectively, and no treatment-related deaths.Extensive development footprintBesides TNBC, the bispecific is being investigated in lung cancer indications as part of the pivotal ROSETTA clinical programme. Two mid-stage studies in extensive-stage small-cell lung cancer read out favourably this year — first in a Chinese population and second in a global one. Meanwhile, the asset is also being explored in non–small-cell lung cancer and mesothelioma (for more, see Spotlight On: Combos key to BioNTech’s PD-L1/VEGF bispecific strategy). “The activity we see in TNBC…further supports the pan-tumour potential of pumitamig, which we are advancing…in a broad development programme that also includes novel/novel combination regimens,” remarked Özlem Türeci, BioNTech’s chief medical officer.Interest in PD-(L)1/VEGF bispecifics started gaining traction last year when Akeso Biopharma and Summit Therapeutics indicated that ivonescimab could potentially unseat Merck & Co.’s Keytruda (pembrolizumab) in lung cancer. Merck soon responded, securing rights to LM-299 from LaNova Medicines in a $588-million upfront deal.

iStock, Rawpixel The partnership will focus on Crescent’s PD-1/VEGF inhibitor CR-001 and Kelun-Biotech’s SKB105, both of which the companies plan to push into Phase I/II development for solid tumors early next year. Massachusetts-based Crescent Biopharma is joining with China’s Sichuan Kelun-Biotech to develop PD-1/VEGF bispecific and antibody-drug conjugate combinations in a partnership worth as much as $1.25 billion. Each company will bring a therapy to the collaboration. Crescent’s CR-001 is a PD-1/VEGF bispecific antibody, while Kelun’s SKB105 is an antibody-drug conjugate (ADC) targeting the integrin beta-6, a protein commonly overexpressed in malignancies. Under the terms of the agreement, announced Thursday , Crescent will front $80 million and promise milestone payments reaching $1.25 billion for rights to SKB105 outside the Greater China region. Kelun will also be eligible to receive royalties on sales of the drug. Meanwhile, the Chinese company will hand Crescent $20 million upfront, as well as pledge up to $30 million in milestones, plus royalties on CR-001 sales inside China. The partners will test both molecules as monotherapies or in combination with each other for solid tumors, the companies said on Thursday. Both candidates are set to enter Phase I/II development in the first quarter of 2026. PD-1/VEGF bispecifics like CR-001 have garnered much attention over the past year, after Summit Therapeutics and Akeso’s ivonescimab in September 2024 claimed victory over Merck’s Keytruda—a cornerstone cancer therapy—in a late-stage study of non-small cell lung cancer. Excitement over ivonescimab has since mellowed, tempered by concerns that its data, generated largely in China, won’t be applicable to the U.S. patient pool. Still, the modality has proven to be an attractive area of investment. Merck partnered with Shanghai-based LaNova Medicines in November 2024 to enter the ring. The pharma paid $588 million upfront and bet $2.7 billion in milestones for LaNova’s LM-299, in early development for solid tumors. Pfizer inked a licensing deal with 3SBio for $1.25 billion upfront and up to $4.8 billion in milestones, gaining access to the Chinese biotech’s bispecific antibody SSGJ-707. A month later, Bristol Myers Squibb put roughly $11 billion on the line to collaborate on BioNTech’s BNT-327. The other half of Thursday’s deal—Kelun-Biotech’s SKB105—also belongs to an emerging, though more established, class of cancer therapies. Fewer than 20 ADCs have been approved by the FDA, giving drugmakers enough room to join the field. In October, Takeda made an $11.4-billion play with China’s Innovent, gaining co-development rights to two ADCs for a variety of cancers. Days earlier, Roche also looked Eastward and put down more than $1.5 billion for Hansoh Pharmaceutical’s ADC for colorectal cancer.