Mersana’s discontinuation was a long time coming

Citing the negative outcome of its phase 1/2 Uplift trial in platinum-resistant ovarian cancer Mersana has discontinued development of upifitamab rilsodotin, as well as moving to cut its workforce by 50%. Disappointing though this is, the failure of Uplift should not come as a surprise: Mersana had presented several increasingly unconvincing cuts of this study in recent years. Not only that, but upifitamab rilsodotin, an NaPi2b-targeting antibody-drug conjugate previously known as XMT-1536, was put on partial hold in June over risk of bleeding events. Mersana had also spent some time tinkering with the addressable patient population, and after it became clear that its chances of a broad label were low it zeroed in on patients with tumours expressing NaPi2b at 75% or above. Ultimately, however, even in this population Uplift failed to clear a threshold of 12% in the lower bound of the confidence interval for investigator-assessed ORR; the final number came in at 15.6%, with a 95% confidence interval of 10.0-22.7%. According to OncologyPipeline just one NaPi2b-targeting ADC now remains in development – Zymeworks’ preclinical-stage ZW220.  Various iterations of upifitamab rilsodotin's Uplift trial Data cutoffORRORR in NaPi2b-high patientsDuration of responseAsco 20201 May 202035% (7/20)29% (4/14)Not reachedEsmo 202018 Aug 202034% (10/29)35% (7/20)Not reachedJan 2021 update3 Dec 202028% (13/47)32% (10/31)~5mth in 10 NaPi2b-high patientsSep 2021 update10 Jun 202123% (17/75)34% (13/38)~5mth in 13 NaPi2b-high patientsJul 2023 update27 Jul 202313% (35/268)16% (22/141)7.4mth in 22 NaPi2b-high patientsNote: High NaPi2b expression defined as tumour proportion score (TPS) ≥75%. Source: company presentations.