Ash 2022 – following in talquetamab’s slipstream

Roche and Bristol Myers Squibb look to have the industry’s next most advanced assets against GPRC5D.

In Johnson & Johnson’s talquetamab, which featured at Ash yesterday, the industry might soon have a brand new approach for treating multiple myeloma. But what are other companies doing to develop rival therapies that hit the same target, GPRC5D?

Two Ash sessions provided an answer this weekend. Roche’s forimtamig, a me-too T-cell engager bispecific also being studied in IV and SC forms, put up results that appeared to come up short of talquetamab. And Bristol Myers Squibb’s Car-T therapy BMS-986393 yielded first-in-human data said to back its potential irrespective of prior BCMA-directed therapy.

It was a legacy Bristol asset that kicked off interest in GPRC5D. Back at Ash 2018 MCARH109, a Car-T against this antigen, was said to have preclinical potential. MCARH109 was then the property of Juno, which had recently been acquired by Celgene, and later Bristol bought out Celgene.

However, BMS-986393 appears to be a different asset. In a relapsed/refractory multiple myeloma population of 33 patients, 18 of whom had received prior anti-BCMA therapy, Bristol reported no treatment-related deaths, and a relatively low 6% rate of severe cytokine release syndrome (CRS).

Across all doses, 17 of 19 efficacy-evaluable subjects went into remission, comprising a 100% ORR in the 10 who had not had prior anti-BCMA therapy, and 78% in the nine who had progressed on Carvykti, ALLO-715, Blenrep or an investigational bispecific.

BMS-986393 efficacy. Source: Dr Jesus Berdeja & Ash.

J&J’s talquetamab has also shown activity in BCMA-naive and experienced patients alike, though whether it will be approved in both is up to the FDA.

Meanwhile, Roche’s forimtamig dataset (the asset had previously been coded RG6234) comprised 50 subjects given an IV and 57 given a SC dose; just over 20% had previously received anti-BCMA therapy. Here severe CRS was higher, at over 30%, and one death in the SC cohort was deemed related to forimtamig.

Response rates were better with IV than with the SC dose, at 71% and 64% respectively, and evaluation and optimisation of both dosing strategies was said to be ongoing. In reality, however, Roche will likely only be able to compete with SC forimtamig, since J&J’s talquetamab filing was for two SC doses.

On a cross-trial basis Roche might have some more work to do, as yesterday’s Ash data put talquetamab’s ORR above the 70% threshold, and the J&J project was associated with only a 2% rate of severe CRS. No other GPRC5D projects appear to be in clinical development in the west.

Source: Dr Carmelo Carlo-Stella & Ash.

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