FDA Grants Fast Track Designation to Opamtistomig for Advanced Biliary Tract Cancer

The FDA has granted fast track designation to opamtistomig (LBL-024), a PD-L1/4-1BB bispecific antibody, for the first-line treatment of patients with advanced or metastatic biliary tract cancer (BTC).¹

The designation follows preliminary findings from a phase 2 study (NCT07111546) evaluating opamtistomig in combination with chemotherapy.^1,2 In an April 2026 update, findings from the safety run-in cohort (n = 20) showed the combination was generally well tolerated, with no new safety signals observed. Preliminary efficacy data demonstrated encouraging tumor reduction trends, and these findings collectively supported progression into the expansion phase, which has completed enrollment.^3,4 The study is led by Jian Zhou, MD, PhD, of Zhongshan Hospital at Fudan University in Shanghai, China, and is being conducted across multiple clinical sites in the country.⁴

“The FDA’s decision to grant fast track designation just 9 days after submission is an encouraging milestone for opamtistomig and our first-line BTC program. We appreciate the FDA’s engagement and its recommendation to initiate discussions on the United States registration strategy for opamtistomig in combination with chemotherapy,” Charles Cai, chief medical officer of Leads Biolabs, stated in a news release.¹ “BTC represents a significant unmet medical need, and immunologically cold tumors remain a major challenge for cancer immunotherapy. Opamtistomig’s differentiated PD-L1/4-1BB mechanism is designed to address this challenge by combining immune checkpoint blockade with conditional T-cell costimulation. Across multiple difficult-to-treat tumor types, we have observed encouraging clinical signals that support further exploration of its potential. We will continue to advance our clinical programs with scientific rigor and executional focus, working closely with regulatory authorities to accelerate development and bring potentially meaningful new treatment options to patients worldwide.”

What is the mechanism of action of opamtistomig?

Opamtistomig is designed to simultaneously inhibit PD-L1–mediated immune suppression and selectively activate the 4-1BB costimulatory pathway.^1,3,4 This dual approach aims to restore T-cell function and expand effector T-cell populations within the tumor microenvironment, providing a rationale for investigation in tumors that respond poorly to checkpoint blockade alone.

The investigational antibody is intended to pair relief of immune suppression with enhanced antitumor immune activity. Its development in BTC is exploring whether combining these complementary immune mechanisms with chemotherapy can improve treatment activity in this disease setting.

How is the phase 2 trial designed?

The open-label, multicenter, phase 2 trial is evaluating opamtistomig-based combinations in 2 cohorts: opamtistomig plus gemcitabine and cisplatin (cohort A), and opamtistomig plus bevacizumab (Avastin; cohort B).²

Investigators enrolled approximately 140 patients 18 to 75 years of age with advanced BTC or hepatocellular carcinoma who had an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, at least 1 measurable lesion, and adequate organ and bone marrow function. Key exclusions include active infections requiring intravenous treatment, clinically uncontrolled effusions or ascites, and recent participation in another antineoplastic drug study.

Each cohort includes a safety run-in followed by expansion. In cohort A, opamtistomig is being given in combination with cisplatin and gemcitabine, and in cohort B, it is being administered in combination with bevacizumab.

The primary end point is objective response rate per RECIST 1.1 criteria. Secondary end points include disease control rate, duration of response, pharmacokinetics, and immunogenicity.

This is the second FDA fast track designation for opamtistomig, following its January 2026 designation for extrapulmonary neuroendocrine carcinoma.¹ Detailed BTC clinical data are planned for presentation at the 2026 ESMO Congress in October.⁴

References

1. Leads Biolabs’ opamtistomig (PD-L1/4-1BB bispecific antibody) granted FDA fast track designation for first-line advanced or metastatic biliary tract cancer. News release. Leads Biolabs. October 12, 2026. Accessed October 12, 2026. https://en.leadsbiolabs.com/pressCenter/detail/dynamicDetail?id=271
2. A clinical trial of LBL-024 combination drug in patients with advanced solid tumours [substudy 02 (BTC&HCC)]. ClinicalTrials.gov. Updated September 21, 2026. Accessed October 12, 2026. https://clinicaltrials.gov/study/NCT07111546
3. Leads Biolabs’ opamtistomig (PD-L1/4-1BB bispecific antibody) advances to expansion phase in first-line biliary tract cancer following positive safety and preliminary efficacy results. News release. Leads Biolabs. April 9, 2026. Accessed October 12, 2026. https://www.globenewswire.com/news-release/2026/04/09/3270693/0/en/Leads-Biolabs-Opamtistomig-PD-L1-4-1BB-Bispecific-Antibody-Advances-to-Expansion-Phase-in-First-Line-Biliary-Tract-Cancer-Following-Positive-Safety-and-Preliminary-Efficacy-Results.html
4. Leads Biolabs’ opamtistomig (PD-L1/4-1BB bispecific antibody) completes patient enrollment in phase II study for biliary tract cancer, further demonstrating breakthrough potential in immune-cold tumors. News release. Leads Biolabs. July 30, 2026. Accessed October 12, 2026. https://www.globenewswire.com/news-release/2026/07/30/3335874/0/en/leads-biolabs-opamtistomig-pd-l1-4-1bb-bispecific-antibody-completes-patient-enrollment-in-phase-ii-study-for-biliary-tract-cancer-further-demonstrating-breakthrough-potential-in-i.html