ESMO26: Zai and Ideaya showcase DLL3 drugs in lung cancer
National Cancer Institute
Two drugs hoping to muscle in Amgen's first-to-market DLL3-targeting drug Imdelltra – from Zai Lab and Ideaya – have new trial readouts at ESMO.
DLL3 is a protein that is found in a majority of small cell lung cancer (SCLC) and neuroendocrine carcinomas (NECs), potentially up to 96%, but is rarely found in healthy cells.
Zai reveals frontline data with zoci ahead of pivotal trial
Zai Lab presented phase 1b data with antibody-drug conjugate (ADC) zocilurtatug pelitecan (zoci) in combination with Roche's PD-L1 inhibitor Tecentriq (atezolizumab), with and without carboplatin chemotherapy, as first-line treatment for extensive-stage small cell lung cancer (ES-SCLC).
The results showed that at a dose of 1.6 mg/kg – which will be used in an international phase 3 trial in treatment-naïve ES-SCLC that is due to start before the end of the year – zoci plus Tecentriq achieved a confirmed objective response rate (ORR) of 81.8%, with nearly 82% of patients living for at least six months without disease progression or death. Adding in carboplatin hiked the ORR to 92.3%, with a trade-off of much more frequent serious (Grade 3 or higher) side effects with the triple therapy.
Frontline use would position the ADC ahead of Imdelltra (tarlatamab) in the treatment pathway, as Amgen's drug is currently approved only for ES-SCLC patients whose disease has progressed on or after platinum-based chemotherapy. That said, Amgen already has results in hand in previously untreated ES-SCLC from the DeLLphi-305 study, an indication that, if approved, could drive the drug into blockbuster sales territory. It made $627 million in 2025, its first full year on the market.
Zai said the new data suggest zoci plus a PD-1/PD-L1 inhibitor could offer a chemo-free regimen to ES-SCLC patients, allowing patients to stay on treatment longer with potentially fewer side effects.
Ideaya/Hengrui update phase 1 results with ADC in relapsed SCLC
Another DLL3-targeting ADC, Ideaya and Hengrui's IDE849 (also known as SHR-4849), revealed promising overall survival (OS) results in relapsed SCLC, including an ORR of 72.5% and a confirmed ORR of 60.8% when used as a second-line therapy.
The 122-subject study, carried out by Hengrui in a Chinese population, revealed a 17.4-month median OS when IDE849 was used second-line, and 14.7 months for the overall cohort, which also included a third-line or later treatment population. There were also promising signs of efficacy I patients whose cancer had spread to the brain, with an ORR and cORR of 76.9% and 65.4%, respectively.
The trial also revealed preliminary signs of efficacy in 19 patients with NECs, with an ORR of 52.6% and cORR of 36.8%.
South San Francisco biotech Ideaya licensed rights to IDE849 from Shanghai-based Hengrui in 2024, in a deal valued at up to $1.045 billion, including a $75 million upfront fee.
Ideaya, which has rights to the ADC outside Greater China, said it plans to start two phase 3 registration trials of the drug in relapsed ES-SCLC (after Imdelltra) and NEC. It is also looking into the design of a frontline SCLC study that could include combination treatment with either its PARG inhibitor IDE161 or AstraZeneca's PD-L1 inhibitor Imfinzi (durvalumab).
