ESMO: Can BioNTech’s revved-up CAR-T hit solid tumours?

CAR-T therapies have transformed the treatment of some haematological cancers, but haven’t made much headway for solid tumours – although BioNTech thinks it may have the key to unlock the door to wider use.

At ESMO, the mRNA specialist reported updated results from its phase 1/2 trial of its lead candidate BNT-211, which consists of a CAR-T directed at Claudin-6 coupled with an mRNA vaccine (CARVac) designed to amplify the activity of the cell therapy.

The new results reinforce data presented at ASCO earlier this year, showing an overall response rate (ORR) of 45% in a group of 38 evaluable patients with various solid tumours that had resisted multiple prior lines of therapy, including germ cell tumours and ovarian cancer, with a disease control rate of 74%.

A subset of 27 patients treated with a 1x108 CAR-T cell dose with or without the CARVac component, showed an ORR of 59%, all partial responses, while 95% of subjects saw their cancer stabilise.

Those who received the mRNA vaccine showed prolonged persistence of CAR-T cells in the body, which, if borne out in further study, could counteract the well-documented issue of relapse after this form of cell therapy.

BioNTech said the trial results are still being evaluated in order to select a dose to take forwards into a phase 2 trial in germ cell tumours like testicular and endometrial cancer next year, which if positive could support regulatory filings.

So far, CAR-Ts have disappointed as therapies for solid tumours as the immune cells find it difficult to target cancer cells, as well as infiltrate and survive in the hostile microenvironment of the tumour.

“BNT211 aims to address two of the key limitations of CAR-T cell approaches in solid tumours, namely, the lack of suitable cancer-specific cell surface targets and the limited persistence of CAR-T cells,” said Professor Özlem Türeci, co-founder and chief medical officer at BioNTech.

“Our goal is to unlock the potential of CAR-T […] and to help improve the outcomes for a broad range of hard-to-treat tumours,” she added.

The German biotech has tweaked its manufacturing process for BNT-211 in an effort to improve its potency, but, as might be expected, that has been accompanied by additional toxicities - a perennial issue with CAR-Ts.

Cytokine release syndrome (CRS) – one of the most serious side effects of the therapy - occurred in 23 of 44 patients evaluable for safety, but most cases were mild to moderate (grade 1 or 2) with one grade 3 requiring hospitalisation and one grade 4 life-threatening, but not fatal, event.

Neurotoxicity – another common complication of CAR-T therapy - was seen in two subjects and was “mild and self-limiting,” according to BioNTech.