In further validation of the DLL3 target pioneered by Amgen’s Imdelltra, the T-cell engager has delivered an overall survival win in first-line small cell lung cancer (SCLC).
Imdelltra, used together with AstraZeneca’s Imfinzi, led to a “statistically significant and clinically meaningful” improvement in overall survival (OS) compared with Imfinzi alone as a first-line maintenance treatment for extensive stage SCLC, Amgen announced Tuesday.
The Imdelltra regimen also showed superior progression-free survival and objective response rate, with safety consistent with the drugs’ known profiles, the company added.
The results from the phase 3 DeLLphi-305 trial could move Imdelltra into earlier treatment of SCLC, which is an aggressive form of lung cancer. SCLC affects about 13% to 15% of more than 2.6 million lung cancer cases diagnosed globally each year, but only about 40% of patients reach second-line therapy, where Imdelltra is currently approved, according to data cited by Amgen.
The California company said it will share the data with regulatory authorities and with the medical community at an upcoming conference.
In a Sept. 8 statement, Amgen’s R&D chief, Jay Bradner, M.D., said the DeLLphi-305 trial suggests Imdelltra “will further revolutionize the standard for survival earlier in the treatment journey and meaningfully shift the treatment paradigm” for ES-SCLC patients.
Despite clinical advances in ES-SCLC, “substantial improvements in survival are rare, underscoring the importance of these findings,” Bradner added.
Detailed results will help industry watchers appraise Imdelltra’s commercial opportunity. Recently, Jazz Pharmaceuticals’ Zepzelca improved patients’ OS by 27% when added to Roche’s Tecentriq, also in the first-line maintenance setting of ES-SCLC. Patients who took Zepzelca and Tecentriq lived a median 13.2 months, versus 10.6 months in the Tecentriq arm. Based on that phase 3 win from the IMforte trial, the Zepzelca-Tecentriq combo secured an FDA approval about a year ago.
By comparison, Imdelltra plus PD-L1 inhibitor treatment had shown an unprecedented 25.3-month median OS as first-line maintenance for ES-SCLC in the phase 1b DeLLphi-303 trial.
In both IMforte and DeLLphi-305, patients had responded to initial treatment with a PD-L1 inhibitor, plus chemotherapy, but had not progressed.
Imdelltra got an initial accelerated approval for previously treated SCLC in 2024 and became the first DLL3-targeted agent to reach the market. The go-ahead was converted into a full nod last year based on another OS win from the phase 3 DeLLphi-304 trial.
Success of Imdelltra has drummed up interest in DLL3 as a target. In 2024, Merck & Co. bought Harpoon Therapeutics for $680 million and has been working to combine the deal’s DLL3 bispecific, MK-6070, with Daiichi Sankyo-partnered B7-H3-directed antibody-drug conjugate, I-DXd, in SCLC.
Roche obtained a DLL3 ADC from Innovent Biologics, and AbbVie got itself a DLL3-directed trispecific T-cell binder from China’s Zejing Biopharmaceutical at the beginning of 2026.
Novartis has partnered with Legend Biotech on DLL3 autologous CAR-T, and Boehringer Ingelheim recently advanced its DLL3 T-cell engager, obrixtamig, into phase 3 testing for SCLC.
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