Opamtistomig (LBL-024) monotherapy in advanced extra-pulmonary neuroendocrine carcinoma (EP-NEC) after ≥2 prior lines of therapies: Results from a pivotal, registrational phase IIb study of a novel PD-L1×4-1BB bispecific antibody

LBL-024

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In patients with advanced extra-pulmonary neuroendocrine carcinoma after at least two prior lines of therapy, opamtistomig monotherapy achieved an independently assessed objective response rate of 26.0%, meeting the prespecified threshold.

N

96pazienti

Disegno

Pivotal, registrational, single-arm phase IIb study of opamtistomig monotherapy in patients with advanced extra-pulmonary neuroendocrine carcinoma after ≥2 prior lines of therapy including platinum-based chemotherapy (NCT05170958).

Esito

Objective response rate assessed by independent review committee in the full analysis set.

RisultatoIRC-assessed ORR 26.0% (25/96; 95% CI 17.6-36.0), meeting the prespecified primary endpoint (lower bound of the 95% CI exceeding the 13% threshold). ORR per iRECIST 29.2% (95% CI 20.3-39.3). Median DoR 9.2 months, median PFS 1.4 months per RECIST 1.1 and 2.8 months per iRECIST, median OS 8.7 months, 12-month OS rate 41.4%, median follow-up 14.8 months. ORR 43.8% without liver metastasis vs 17.2% with liver metastasis, median PFS 4.2 vs 1.4 months. TRAEs occurred in 92.7% (89/96), grade ≥3 in 28.1% (27/96).

Lu M, Zhang P, Chen J, et al. Presented at ESMO Congress 2026, abstract LBA57, 26 October. Not yet published.

Discussione e critica

The study met its prespecified response threshold, with about one in four heavily pretreated patients responding and responses lasting a median of 9.2 months. It is single-arm, so the response rate, the median OS of 8.7 months and the durability of responses cannot be compared with any control, and ORR is a surrogate rather than a hard endpoint. A median PFS of 1.4 months per RECIST 1.1 shows that most patients progressed quickly, and the stronger activity without liver metastasis comes from an exploratory subgroup of 32 patients. PD-L1 status was available for only 39 of 96 patients, and the abstract gives no breakdown by primary tumour site or details of the adverse events beyond overall rates.