ESMO 2024 preview – Summit could take on Merck in breast cancer
Early data suggest that PD-(L)1 x VEGF bispecifics might challenge Keytruda in triple-negative disease.
Early data suggest that PD-(L)1 x VEGF bispecifics might challenge Keytruda in triple-negative disease.
Summit and Akeso have already claimed a win with ivonescimab versus Keytruda in first-line lung cancer, and data released in an ESMO abstract this week suggest that the project could also have an edge in front-line triple-negative breast cancer.
This is from a small Chinese study, so ivonescimab still has much to prove. But this might not be the only problem for Summit: BioNTech is set to report corresponding data at ESMO with its similarly acting project, BNT327 – and the German group is ahead, having recently started a global phase 2 study in TNBC.
First-line face off
Monday will see the presentation of results with both ivonescimab and BNT327 in first-line TNBC, from early to mid-stage Chinese trials testing the agents in combination with chemo.
While ivonescimab targets VEGF and PD-1, BNT327 – which BioNTech licensed from Biotheus – hits VEGF and PD-L1. BioNTech has previously hinted that this slight difference might give its project the edge – but based on the ESMO abstracts the two assets look very similar, at least in TNBC.
Importantly, both appear to be performing well in patients with low PD-L1 expression. This is notable as Keytruda monotherapy, which is approved in first-line TNBC, is indicated only for patients with PD-L1 expression of 10% or more.
This could give BioNTech and Summit a niche to aim for: those with PD-L1 expression below 10%. But the companies might also want to take on Keytruda in all comers, given a favourable cross-trial comparison here too.
Cross-trial comparison in first-line TNBC
Ivonescimab | BNT327 | Keytruda | |
|---|---|---|---|
| Company | Summit/Akeso | BioNTech/Biotheus | Merck & Co |
| Study | Ph2 China | Ph1/2 China | Keynote-355 |
| Cutoff | 1 Mar 2024 | 15 Mar 2024 | N/A |
| ORR | 72% (21/29)* | 74% (31/42)** | 41% (231/566)** |
| ORR in ≥10% PD-L1 | 83% (5/6)* | 100% (9/9) | 53% (116/220)** |
| ORR in <10% PD-L1 | 70% (16/23)* | – | 33% (115/346)** |
| ORR in ≥1% PD-L1 | – | 72% (18/25) | 45% (191/425)** |
| ORR in <1% PD-L1 | – | 77% (10/13) | 28% (40/141)** |
Notes: *by investigator assessment; **confirmed ORR. Source: ESMO.
PFS data for ivonescimab weren’t mature, but median PFS with BNT327 was 13.3 months – above the 7.5-month median PFS seen in all comers with Keytruda plus chemo in the Keynote-355 study.
Such cross-trial comparisons are obviously fraught with danger, especially given that the studies of ivonescimab and BNT327 were small, uncontrolled and based in China, while Keynote-355 was much larger, global, and featured a chemo control arm.
Still, this is more good news for Summit, which has seen its stock rocket 85% this week, and is now sitting on a $16bn valuation – not all that far from BioNTech’s $24bn market cap.
One dark spot for the PD-(L)1 x VEGF projects could be toxicity, with around 50% of patients experiencing grade 3 or higher adverse events. Still, there were no treatment-related deaths in either trial, according to the abstracts.
BioNTech has begun a phase 2 global trial in first and second-line TNBC; its inclusion criteria don’t specify a predetermined PD-L1 expression level.
Meanwhile, Summit’s US trials of ivonescimab are so far confined to NSCLC – although the company hinted at plans in TNBC when it announced a $235m in a private fund raising today.
ESMO will take place in Barcelona, Spain, on 13-17 September 2024.
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