ESMO 2024 preview – Summit could take on Merck in breast cancer

12 September 2024

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 offMonday 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 IvonescimabBNT327KeytrudaCompanySummit/AkesoBioNTech/BiotheusMerck & CoStudyPh2 ChinaPh1/2 ChinaKeynote-355Cutoff1 Mar 202415 Mar 2024N/AORR72% (21/29)*74% (31/42)**41% (231/566)**ORR in ≥10% PD-L183% (5/6)*100% (9/9)53% (116/220)**ORR in <10% PD-L170% (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.

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.