FDA Grants Fast Track Designation to LBL-024 in Extrapulmonary NEC

The FDA has granted fast track designation to the PD-L1/4-1BB bispecific antibody LBL-024 (Opamtistomig) for the treatment of patients with extrapulmonary neuroendocrine carcinoma (EP-NEC), according to a press release from the developer, Nanjing Lead Biolabs Co.¹

Supportive results for LBL-024 come from 2 clinical trials in China, in which LBL-024 yielded positive efficacy with favorable safety among patients with advanced EP-NEC. The first was a first-in-human phase 1/2 trial (NCT05170958), which evaluated LBL-024 as monotherapy.² The second was a phase 1b/2 trial (NCT06157827), which evaluated LBL-024 in combination with etoposide/platinum-based chemotherapy in treatment-naïve advanced EP-NEC.³

LBL-024 as Monotherapy

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, investigators shared data from a dose-escalation and dose-expansion study evaluating LBL-024 as monotherapy. In the phase 1 portion of the study, patients received escalating doses of LBL-024 ranging from 0.2 mg/kg to 25 mg/kg.

At 0.8 mg/kg (n = 1), 100% of patients achieved a partial response (PR); at 3.2 mg/kg (n = 5), 40.0% of patients experienced a PR, and 60.0% had progressive disease; at 6 mg/kg (n = 1), 100.0% of patients had progressive disease; at 10 mg/kg (n = 5), 20.0% experienced a PR, 60.0% had stable disease, and 20.0% had progressive disease; and at 15 mg/kg (n = 3), 33.3% experienced a PR, 33.3% had stable disease, and 33.3% had progressive disease.

In the phase 2 portion of the study, patients received 15 mg/kg of LBL-024 (n = 32). Among all patients, 31.3% experienced a PR, 12.5% had stable disease, 50.0% had progressive disease, and 6.3% were not done with treatment. Of the patients treated in the second line of therapy (n = 17), 35.3% had a PR, 11.8% had stable disease, and 47.1% had progressive disease. Among those treated in the third line of therapy or later (n = 18), 27.8% experienced a PR, 16.7% had stable disease, and 50.0% had progressive disease.

At the recommended phase 2 dose (RP2D) of 15 mg/kg, the overall response rate (ORR) was 33.3%, and the disease control rate (DCR) was 48.5%.

Eligible patients in the trial were 18 years or older and had previously progressed on standard-of-care treatment, an ECOG performance status of 0 or 1, and adequate organ function. All patients in the phase 2b portion had EP-NEC confirmed by central lab, which had already been treated by at least 2 lines of chemotherapy.

The primary end points of the phase 1 portion were safety and tolerability, and the RP2D; secondary end points were pharmacokinetics, immunogenicity, and efficacy. In the phase 2 portion, the primary end point was the ORR; the secondary end points were safety, immunogenicity, duration of response, and progression-free survival.

Regarding safety, of patients treated at the RP2D, treatment-emergent adverse events (TEAEs) and treatment-related AEs (TRAEs) occurred in 88.3% and 70.3% of patients, respectively. Serious AEs and treatment-related serious AEs occurred in 33.3% and 15.3%. Additionally, grade 3 or higher AEs and TRAEs occurred in 36.9% and 16.2%. Furthermore, TRAEs led to interruption or discontinuation in 22.5% and 2.7%.

The most common any-grade TEAEs were anemia (33.1%), aspartate aminotransferase increase (32.6%), alanine aminotransferase increase (27.4%), and leukopenia (27.4%). The most common grade 3 or higher TEAEs were anemia (5.1%), leukopenia (3.4%), neutropenia (2.9%), and hypokalemia (2.9%).

LBL-024 with Chemotherapy

At the 2025 ASCO Annual Meeting, results from the phase 1b/2 trial evaluating LBL-024 in combination with etoposide/platinum-based chemotherapy were shared. With a data cutoff of April 15, 2025, and a median follow-up of 8.2 months, 52 patients were evaluable for efficacy. The ORR and DCR were 75.0% and 92.3%, respectively, with 1.9% having CRs, 73.1% PRs, 17.3% stable disease, and 7.7% progressive disease.

In the phase 1b dose-escalation portion of the trial, 3 patients received 6 mg/kg of LBL-024, of whom 2 had PRs and 1 had stable disease; 6 patients received 10 mg/kg, of whom 4 had PRs, 1 had stable disease, and 1 had progressive disease; and 6 patients received 15 mg/kg, of whom 4 had PRs and 2 had progressive disease. In the phase 2 dose-optimization phase, patients received either 6 mg/kg (n = 19) or 15 mg/kg (n = 18) of LBL-024. In the 6 mg/kg group, the ORR was 73.7%, and the DCR was 94.7%, with 73.7% having PRs, 21.1% stable disease, and 5.3% progressive disease. In the 15 mg/kg group, the ORR was 83.3%, and the DCR was 100.0%, with 5.6% having CRs, 77.8% PRs, and 16.7% stable disease.

Notably, 57.7% of efficacy-evaluable patients experienced more than 50% tumor shrinkage.

Eligible patients in the trial had histologically and/or cytologically confirmed NEC that had not previously received systemic treatment.

In phase 1b, treatment consisted of intravenous LBL-024 from 6 mg/kg to 15 mg/kg every 3 weeks, with etoposide plus cisplatin or etoposide plus carboplatin. Then, in the phase 2 portion, patients were randomly assigned to receive LBL-024 at 6 mg/kg or 15 mg/kg, with either of the etoposide regimens. Finally, in the dose-expansion portion of phase 2, patients received LBL-024 at 15 mg/kg with one of the etoposide regimens. Etoposide was given intravenously at 100 mg/m² on days 1 to 3, with either cisplatin intravenously at 75 mg/m² on day 1 every 3 weeks for up to 6 cycles, or carboplatin intravenously at area under the curve 5 mg/mL/min on day 1 every 3 weeks for up to 6 cycles.

Regarding safety, any TEAE occurred in 100.0% of patients, with TRAEs occurring in 98.2%. Grade 3 or higher TEAEs and TRAEs occurred in 89.1% and 80.0%, respectively. TRAEs led to interruption, treatment discontinuation, and death in 63.6%, 3.6%, and 1.8%, respectively. The most common grade 3 or higher TEAEs were neutropenia (61.8%), leukopenia (36.4%), thrombopenia (25.5%), and anemia (21.8%).

References

1. Voluntary announcement LBL-024 (Opamtistomig, PD-L1/4-1BB bispecific antibody) granted fast track designation by the U.S. FDA. News release. Nanjing Leads Biolabs. January 14, 2026. Accessed January 20, 2026. https://tinyurl.com/b4xyusu
2. Lu M, Zhang P, Luo S, et al. A novel and uniquely designed bispecific antibody (LBL-024) against PD-L1 and 4-1BB in patients with advanced malignant tumors and neuroendocrine carcinoma: A report of safety and robust efficacy of LBL-024 monotherapy in phase I/II, first-in-human, open-label, multicenter, dose escalation/expansion study. J Clin Oncol. 2024;42(suppl 16):4010. doi:10.1200/JCO.2024.42.16_suppl.4010
3. Lu M, Zhang P, Liu B, et al. Assessment of efficacy of LBL-024, a novel and uniquely designed bispecific antibody against PD-L1 and 4-1BB, combined with etoposide/platinum-based chemotherapy in treatment-naive advanced extrapulmonary neuroendocrine carcinoma (EP-NEC): A multicenter phase Ib/II trial. J Clin Oncol. 2025;43(suppl 16):2500. doi:10.1200/JCO.2025.43.16_suppl.250