Mersana's upri disappoints again


Hopes for Mersana’s NaPi2b-targeting antibody-drug conjugate upifitamab rilsodotin had already dimmed after a lacklustre data drop in January. Now they have taken another hit with an update from the same trial, in heavily pretreated ovarian cancer, showing shrinking efficacy across the overall population. Mersana claimed a better result in high NaPi2b expressers, but 14 patients had unknown NaPi2b status, and 22 were excluded from the analysis, mainly owing to deaths and withdrawals. Inclusion of some of these subjects in the NaPi2b-high group could make the latest data cut less flattering. Upri’s toxicity profile also raised eyebrows, with two cases of pneumonitis in the highest-dose group, 43mg/m2. And the project’s efficacy appeared to wane as the dose rose. Mersana has now changed the starting dose for the potentially registrational Uplift portion of the single-arm study to 36mg/m2, from 43mg/m2 previously; the maximum dose is 80mg flat. Leerink analysis contended that upri, previously called XMT-1536, was an active drug in an area of unmet need, but investors clearly disagreed, with the group plunging 39% on Friday. Next up for Mersana is data with upri in non-small cell lung cancer, due in the fourth quarter.

Going down again: the evolution of upifitamab rilsodotin's phase 1 trial
  Asco 2020 Esmo 2020 Jan 2021 update Sep 2021 update
Cut-off date May 1, 2020 Aug 18, 2020 Dec 3, 2020 June 10, 2021
ORR 35% (7/20) 34% (10/29) 28% (13/47) 23% (17/75)
ORR in NaPi2b-high patients 29% (4/14) 35% (7/20) 32% (10/31) 34% (13/38)
ORR in NaPi2b-low patients 25% (1/4) 29% (2/7) 15% (2/13) 9% (2/23)
ORR in NaPi2b-undetermined patients 100% (2/2) 50% (1/2) 33% (1/3) 14% (2/14)
Duration of response Not reached Not reached ~5mth in 10 NaPi2b-high patients ~5mth in 13 NaPi2b-high patients
Note: High NaPi2b expression=tumour proportion score (TPS) ≥75; low NaPi2b expression=TPS <75. Source: company presentations.

Share This Article