The relentless march of VEGF bispecifics
Two new pivotal Chinese first-line trials have started in lung cancer.
Two new pivotal Chinese first-line trials have started in lung cancer.
The PD-(L)1 x VEGF field continues to expand at a rapid pace, with new players and trials emerging almost every month, especially in non-small cell lung cancer.
In just the last two weeks, two more pivotal studies have been posted on the clinicaltrials.gov registry for this indication. The latest entries come from Sinocelltech and Huabo, two Chinese companies that, for now at least, have not scored a partnership with big pharma.
The first of these two studies evaluates Sinocelltech’s PD-1 x VEGF bispecific SCTB14 in first-line NSCLC. The pivotal trial will enrol both squamous and non-squamous patients with PD-L1 expression of 10% or higher and no actionable driver mutations. SCTB14 will be tested head to head against Keytruda, with progression-free survival as a primary endpoint.
Huabo, meanwhile, is expanding its late-stage footprint in NSCLC. After previously posting a pivotal trial in squamous NSCLC it has now registered a second pivotal study for its PD-L1 x VEGF fusion protein sotiburafusp alfa, in non-squamous NSCLC.
Both trials pair the experimental agent with chemotherapy, but the choice of the comparator arm differs by histology: Keytruda plus chemo in squamous, and BeOne’s Tevimbra plus chemo in non-squamous.
The difference in the comparators is notable, particularly as Akeso’s pivotal trial of its Summit-partnered contender ivonescimab in squamous NSCLC, Harmoni-6, uses Tevimbra plus chemo as control arm.
Data backing
Huabo’s confidence in moving both indications into pivotal studies rests on data presented at ESMO.
In non-squamous NSCLC the company reported a 62% response rate among 63 treatment-naive patients treated with sotiburafusp alfa. While those numbers fell short of the 85% ORR seen in 62 squamous patients, the safety profile appeared cleaner, with no grade 5 treatment-related adverse events reported, versus two in the squamous population.
With these two additions, a total of 16 NSCLC pivotal trials evaluating PD-(L)1 x VEGF bispecifics have now been posted on clinicaltrials.gov. And the wave shows little sign of breaking, with Junshi expected to initiate a pivotal neoadjuvant study of JS207, while AbbVie and RemeGen are gearing up to move RC148 into pivotal testing in the first and second-line settings.
Selected PD-(L)1 x VEGF bispecific pivotal studies in first-line NSCLC
| Trial | Sponsor | Indication | Regimen | Status |
|---|---|---|---|---|
| Rosetta-Lung02* | BioNTech | 1st-line, PD-L1 all comers | Pumitamig + chemo, vs Keytruda + chemo | Phase 2 data expected in 2026 |
| Rosetta-Lung202 | Bristol Myers Squibb | 1st-line, PD-L1 ≥50% | Pumitamig, vs Keytruda | To start Apr 2026 |
| SCTB14-A301 | Sinocelltech | 1st-line, PD-L1 ≥10% | SCTB14, vs Keytruda | Started Dec 2025; primary completion Jul 2027 |
| HB0025-C-0303 | Huabo | Non-squam, 1st-line | Sotiburafusp alfa + chemo, vs Tevimbra + chemo | Started Jan 2026; primary completion Apr 2028 |
| HB0025-C-0302 | Huabo | Squam, 1st-line | Sotiburafusp alfa + chemo, vs Keytruda +chemo | Started Jan 2026; primary completion Apr 2028 |
| C461001 | Pfizer | 1st-line, PD-L1 all comers | PF-08634404 + chemo, vs Keytruda + chemo | Started Jan 2026; primary completion Feb 2029 |
| SSGJ-707-NSCLC-III-01 | 3Sbio | 1st-line, PD-L1 ≥1% | PF-08634404, vs Keytruda | Started Jun 2025; primary completion Jul 2026 |
| Harmoni-3 | Summit | 1st-line, PD-L1 all comers | Ivonescimab + chemo, vs Keytruda + chemo | Data due H2 2026 for sq; H1 2027 non-sq |
| Harmoni-7 | Summit | 1st-line, PD-L1 ≥50% | Ivonescimab, vs Keytruda | Started Feb 2025; primary completion Apr 2028 |
| Harmoni-2 | Akeso | 1st-line, PD-L1 ≥1% | Ivonescimab, vs Keytruda | Approved in China Apr 2025 |
| Harmoni-6 | Akeso | Squam, 1st-line | Ivonescimab + chemo, vs Tevimbra + chemo | NDA accepted in China Jul 2025 |
Note: *phase 2/3. Source: OncologyPipeline.
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