Merck KGaA’s North American healthcare business, EMD Serono, is discontinuing a clinical trial for a med once considered a star in its oncology program, but an interim analysis has the company changing tactics.
The med that may be sent packing elsewhere is berzosertib, an ATR inhibitor that was in a phase 2 relapsed, platinum-resistant small cell lung cancer trial. EMD Serono conducted an interim analysis of the DDRiver SCLC 250 trial and found a low probability of success.
EMD Serono has decided to discontinue the trial, but “will continue its open innovation approach” that includes ongoing external studies of berzosertib in other combinations and clinical settings. The DDRiver SCLC 250 trial was assessing the med combined with the chemotherapy topotecan,
“While we did not see the outcomes we hoped for with this combination in this particularly challenging population of patients with platinum-resistant SCLC, we are confident in the potential of ATR inhibition, as a combination with chemotherapy is only one avenue to take advantage of DNA damage response,” said Victoria Zazulina, M.D., head of EMD Serono’s oncology development unit.
The company plans to “assess our path forward” with berzosertib, according to Zazulina, who pointed to another oral ATR inhibitor, M1774, and others in the company’s DNA damage response inhibitors program in the meantime.
But berzosertib had been the lead candidate in EMD Serono’s DNA damage response inhibitor pipeline, a type of cancer therapy that goes after existing defects in DNA repair. The therapy was also being tested in ovarian cancer and various solid tumors. Previously known as M6620, it was licensed from Vertex Pharmaceuticals in 2017.
Berzosertib is listed first on Merck’s phase 2 pipeline—just above now-shelved asset, bintrafusp alfa, the former GlaxoSmithKline-partnered bispecific antibody that crumbled after multiple clinical studies failed.
Elsewhere, EMD Serono is working on the apoptosis proteins inhibitor xevinapant, which is being tested in advanced head and neck cancer. The company has two phase 3 trials: TrilynX is now recruiting patients and XRay Vision is expected to open for enrollment this summer. Xevinapant was licensed last year in a $855 million pact with Swiss biotech Debiopharm.
EMD Serono is also working to bolster Bavencio, which is already approved for urothelial carcinoma, Merkel cell carcinoma and renal cell carcinoma. The company is exploring whether adding a novel therapy to the mix can boost Bavencio’s efficacy in bladder cancer. In a newly opened phase 2 trial called JAVELIN Bladder Medley, Bavencio will be tested alone and in combination with the anti-TIGIT antibody M6223 as a first-line maintenance treatment for patients who have advanced disease.
TIGIT therapies were in the news in May after Roche’s candidate tiragolumab notched a second phase 3 failure, bringing into question whether Big Pharma’s billion-dollar bet was worth the spend. Merck’s M6223 was developed internally, while its peers have spent billions to develop partnerships with other companies to work on the therapies.