Antibody Drug SHR-4849 Shows Early Promise Against Small-Cell Lung Cancer In First Human Trial

A team of Chinese researchers has reported encouraging findings from a first-in-human trial of SHR-4849, a novel antibody-drug conjugate (ADC), offering a potential breakthrough in the treatment of relapsed small-cell lung cancer (SCLC)—a particularly aggressive and hard-to-treat form of lung cancer.

Dr Linlin Wang and colleagues at the Affiliated Cancer Hospital of Shandong First Medical University led the trial and presented their findings at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC).

Small-cell lung cancer (SCLC) grows rapidly and carries a poor prognosis.

The International Agency for Research on Cancer reported that doctors diagnosed 2.48 million people with lung cancer in 2022, with SCLC making up 11.5 per cent of cases in men and 9.7 per cent in women.

Current treatment options remain limited, particularly for relapsed cases.

SHR-4849 (also known as IDE849) targets Delta-like ligand 3 (DLL3), a protein highly expressed in SCLC cells. The drug links a humanised anti-DLL3 monoclonal antibody to a DNA topoisomerase I inhibitor via a cleavable linker, delivering chemotherapy directly to the cancer cells while sparing healthy tissue.

Promising Trial Results

In the Phase I trial, researchers treated 54 patients across five dosage levels (0.8 to 4.2 mg/kg) using a dose-escalation and expansion approach.

Among 42 evaluable patients, the objective response rate (ORR) was 59.5 per cent, and the disease control rate (DCR) reached 90.5 per cent.

Patients who received the 2.4 mg/kg expansion dose saw an even higher ORR of 77.8 per cent.

No dose-limiting toxicities were observed below 4.2 mg/kg, and plasma exposure of the free toxin remained low, supporting the drug’s safety profile.

The most common side effects included decreased white blood cell count, anaemia, neutropenia, and nausea, though none led to treatment discontinuation or death.

Dr Wang stated that dose expansion is ongoing to determine the recommended Phase II dose (RP2D).

She emphasised that the early data support further development of SHR-4849 as a treatment for DLL3-positive relapsed SCLC.

“These encouraging early data support further investigation of SHR-4849 as a potential treatment for patients with DLL3-positive relapsed SCLC,” said Dr Wang during the WCLC presentation.

If further trials confirm its efficacy and safety, SHR-4849 may offer a targeted and effective therapy for a cancer type in desperate need of new options.

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