Astra goes subcutaneous in its Merck race

In the contest to get a next-gen CD19-targeting T-cell engager to market AstraZeneca has put more space between it and its big rival here, Merck & Co. Astra is starting a third phase 3 study of its candidate surovatamig, while Merck is only just about to take its contender, the Curon-originated MK-1045, into its first global trial.

Astra’s latest pivotal study, Soundtrack-C1, will test surovatamig as consolidation therapy in chronic lymphocytic leukaemia and small lymphocytic lymphoma. Notably, the study is evaluating a subcutaneous formulation, marking the first disclosure that Astra is pursuing this route of administration.

Surovatamig was originally developed as an intravenous infusion, which has yielded data from early-stage trials. Two other pivotal studies are already under way, Sountrack-F1 in first-line follicular lymphoma and Soundtrack-D2 in untreated large B-cell lymphoma, but these make no mention of the molecule's route of administration.

It’s possible that the SC version was developed using technology that Astra licensed from the drug delivery specialist Alteogen last year. The companies didn’t give details of the projects covered by the agreement, only saying the deal involved “several oncology assets”.

A SC form of Astra's big ADC blockbuster, Enhertu, is already in development using Alteogen's tech, though that deal is routed via the drug's originator, Daiichi Sankyo.

Pumping Soundtrack

Either way, Astra now looks well ahead of Merck, which is set to start its phase 1/2 study of MK-1045 in May in non-Hodgkin’s lymphoma. Merck acquired global rights to MK-1045, then known as CN201, via a $700m deal with the China’s Curon Biopharmaceutical in 2024. At the time, the asset had produced data from early-stage Chinese studies.

As for surovatamig the new trial, Soundtrack-C1, will have a dose-optimisation/safety portion, and a phase 3 part. It ultimately aims to test surovatamig monotherapy versus observation in patients with immunoglobulin heavy chain variable region-unmutated CLL/SLL following standard-of-care induction therapy. The primary efficacy endpoint will be progression-free survival.

Surovatamig doesn’t appear to have produced clinical data yet in CLL, although the phase 2 Soundtrack-E study across various B-cell malignancies, including CLL, is set to read out this year.

Astra’s decision to jump straight into phase 3 therefore looks daring. Even with Soundtrack-F1 and Soundtrack-D2 the company appeared to be taking a risk, going straight from phase 1 to phase 3. The UK group gained rights to surovatamig via in its 2022 acquisition of the private company Teneotwo for $100m up front. 

Both Astra and Merck are trying to improve on Amgen’s Bite-format anti-CD19 T-cell engager Blincyto, which is approved for relapsed/refractory ALL, but carries boxed warnings of CRS and neurotoxicity.

Meanwhile, Novartis recently abandoned an anti-CD19 x CD2 trispecific T-cell engager, PIT565, in cancer, although autoimmune indications continue.

Phase 3 studies of surovatamig (AZD0486)

Note: *SC surovatamig. Source: OncologyPipeline & clinicaltrials.gov.