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AACR 2024 preview – “cancer vaccines” primed to underwhelm

Projects from the likes of BioNTech, Transgene and Scancell will feature, but still have much to prove.

This year’s AACR conference looks set to have a focus on immunotherapies sometimes referred to as “cancer vaccines”, despite various failures of such assets over the years. And, while a prominent AARC session asks whether this technology is “ready for prime time”, it seems that the answer is no.

Most of the projects listed below, gleaned through a search of AACR abstract titles, are still at a very early stage or even inactive: Boehringer’s Curevac-partnered BI1361849 was discontinued several years ago. Meanwhile, Transgene represents perhaps the most promising approach of recent years, harnessing neoantigens, but based on the title its presentation could be limited to immunogenicity data.

Gritstone, a player whose prominence has been boosted by a key catalyst – results are due any day with its neoantigen contender Granite, in the tough setting of first-line colorectal cancer – does not feature in the AACR titles.

BioNTech vs Boehringer

BioNTech also has a neoantigen contender, the Roche-partnered autogene cevumeran (BNT122), but the most notable data at AACR will come from its so-called “Fixvac” project BNT116. This has a similar design to Boehringer’s abandoned BI1361849, with RNA encoding various tumour-associated antigens; in the case of BNT116, these remain undisclosed.

The signs for BNT116 are not great: preliminary results, presented at SITC last November, found no responses among 10 evaluable advanced NSCLC patients, five receiving BNT116 alone, and five receiving BNT116 plus Libtayo.

Combo confusion

More promising, on the face of it, were data last year on Scancell’s SCIB1, which also has a slot at AACR. Last November the company announced an 85% response rate among 13 first-line advanced melanoma patients in its phase 2 Scope trial.

However, there are reasons to be cautious. As well as the small number of subjects, patients also received Opdivo and Yervoy, and the study is uncontrolled, making it hard to ascertain SCIB1’s contribution. A phase 2/3 registrational trial is being planned.

PDC*line Pharma is also testing its contender PDC*lung01 as monotherapy and in combination with PD-1 inhibition, specifically Keytruda, in NSCLC. That group has reported four partial responses in a six-patient combo cohort, but again it's hard to tease out PDC*lung01’s effect.

 

Notable “cancer vaccine” abstracts at AACR 2024

ProjectCompanyDescriptionIndicationAbstractNote
PDC*lung01PDC*line PharmaPlasmacytoid dendritic cells loaded with 7 antigens (NY-ESO-1, MAGE-A3, MAGE-A4, multi-MAGE, survivin, MUC1, Melan-A)NSCLC +/- anti-PD-1 CT021 Preliminary data at ESMO IO 2022: 4/6 PDC*lung01 + Keytruda pts had partial response
Hiltonol (Poly-ICLC)OncovirdsRNA viral mimic and immunomodulatorProstate cancerCT0231st cohort enrolled in 2019
SCIB1ScancellDNA encoding gp100 and TRP-2 epitopesMelanoma + Opdivo + Yervoy (Scope)CT024Initial data in Nov 2023 showed ORR 85% (11/13 pts)
BNT116BioNTechmRNA encoding 6 antigensNSCLC +/- Libtayo/docetaxel (Luca-Merit-1)CT051Preliminary data at SITC 2023: 0 responses among 10 pts
BI1361849Boehringer Ingelheim/ CurevacmRNA encoding 6 antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1)NSCLC + Imfinzi + ImjudoCT052Programme discontinued 2021
TG4050TransgeneNeoantigen immunotherapyHPV-ve H&NLB401Immunogenicity data due; previous update at ASCO 2023

Source: AACR 2024.