Astra pulls further ahead of Merck’s Curon project

AstraZeneca was already ahead of Merck & Co in the CD19-targeted T-cell engager space, and now the former’s candidate surovatamig has gone further into the lead, with a new phase 3 study set to start in November.

This second pivotal trial of the project will be in first-line elderly or unfit patients with large B-cell lymphoma, according to a new listing on clinicaltrials.gov – joining a study in follicular lymphoma that began last year. In both cases Astra has jumped straight from phase 1 into phase 3.

In the new trial, Soundtrack-D2, surovatamig will be combined with R-mini-CHOP, versus R-mini-CHOP (Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone) alone. There will be a safety run-in, which will also aid dose selection, followed by the phase 3 part, the primary endpoint of which will be progression-free survival.

Phase 3 studies of surovatamig (AZD0486)

Source: OncologyPipeline & clinicaltrials.gov.

Phase 1 results have been reported with surovatamig in DLBCL, most recently at ASCO, where a poster showed ORRs of 46%, 62% and 75% with 7.2mg, 15mg and 25mg respectively, although the last included just eight patients. And ORRs were a respectable 33-50% in patients who had failed CD19-directed Car-T therapy.

Adverse events will be key to dose selection; in phase 1 neutropenia looked particularly notable, being seen at grade 4 in 17% of patients, and there was also a relatively high 20% rate of all-grade ICANS, including 6% at grade 3. The poster didn’t break out adverse events by dose, but did note that high doses weren’t associated with greater rates of toxicity including infections, cytokine release syndrome of ICANS; all CRS events were grade 2 or below, possibly thanks to the project’s low-affinity CD3 binder.

Surovatamig, previously known as AZD0486, is also in the uncontrolled phase 2 Soundtrack-B trial as monotherapy in relapsed/refractory non-Hodgkin’s lymphoma (both follicular lymphoma and DLBCL); results are expected in 2026 or later.

Vs MK-1045

Merck, which gained its project MK-1045 from the Chinese group Curon Biopharmaceutical just over a year ago, doesn’t appear to have started studies outside China, let alone pivotal ones.

And no data are yet available with MK-1045 in DLBCL, this lymphoma subtype being represented in a Chinese phase 1 trial presented at ASCO 2024. Instead, data were reported solely in indolent lymphomas, where MK-1045 produced a 100% response rate among 19 patients receiving target doses of 5mg or higher.

While Merck paid $700m up front for MK-1045 – then known as CN201 – Astra gained AZD0486 in its 2022 acquisition of Teneotwo for $100m up front.

Amgen’s Bite format CD19 T-cell engager Blincyto is approved for relapsed/refractory ALL, but carries black box warnings for CRS and neurotoxicity. Other big clinical-stage players here include Novartis, whose PIT565 also hits CD2, but has been in phase 1 since 2022 with no results yet available. GSK last year bought a CD19/CD20-targeting T-cell engager, CMG1A46, from Chimagen Biosciences, but its main focus appears to be autoimmune disease.