Opamtistomig Earns FDA Fast Track in First-Line Biliary Tract Cancer

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

Following a basket study of opamtistomig monotherapy that showed efficacy in BTC among other solid tumors, opamtistomig is being evaluated with chemotherapy in a phase 2 trial for advanced BTC. It previously received FTD for extrapulmonary neuroendocrine carcinoma (EP-NEC).

“The FDA’s decision to grant [FTD] just [9] days after submission is an encouraging milestone for opamtistomig and our first-line BTC program,” said Charles Cai, chief medical officer of Leads Biolabs in Nanjing, China, in a news release.

Clinical Development of Opamtistomig

Opamtistomig was studied initially as a single agent in a phase 1/2a basket study (NCT05170958) that began in 2022 and has enrolled 175 patients with advanced solid tumors, demonstrating efficacy and safety in tumor types including BTC, platinum-resistant ovarian cancer, PD-1–refractory advanced hepatocellular carcinoma (HCC), and previously treated EP-NEC. The company stated its intention to publish the findings in an international journal.¹

An open-label multicenter phase 2 study (NCT07111546) to evaluate the safety of combination therapy in BTC and HCC is ongoing. The BTC cohort moved into its expansion phase in April 2026 after a 20-patient safety run-in and completed enrollment of all 70 patients as of July 2026.² According to the company, opamtistomig in combination with chemotherapy was generally well tolerated and preliminary efficacy assessments showed encouraging tumor reduction trends.

According to Leads Biolabs, preliminary results in BTC, platinum-resistant ovarian cancer, hepatocellular carcinoma refractory to PD-1 blockade, and previously treated extrapulmonary neuroendocrine carcinoma (EP-NEC) suggest a possible survival benefit.¹ At the World Conference on Lung Cancer in September 2026, opamtistamig plus chemotherapy led to robust and durable antitumor activity in both squamous and nonsquamous non–small cell lung cancer with an overall response rate of 71.0% in 62 evaluable patients.³

Mechanism of Action

The antibody pairs PD-L1 blockade with 4-1BB costimulation that is designed to switch on only within the tumor microenvironment. Leads Biolabs stated that this combination is intended to promote tumor-associated immune suppression while boosting T-cell activity, which may be of particular value in immunologically cold tumors that respond poorly to current immunotherapies.¹

Regulatory Background

The FTD for EP-NEC was granted in January 2026; previous to this, in November 2024, the agency also granted the agent orphan drug designation in neuroendocrine cancer. That designation followed phase 1/2 data (NCT05170958) presented at the 2024 American Society of Clinical Oncology Annual Meeting, in which 45 evaluable patients with EP-NEC who had received at least 2 prior lines of chemotherapy had an objective response rate (ORR) of 33.3% and a disease control rate of 51.1%, with a median duration of response of 5.3 months.⁴

Outside the United States, China’s National Medical Products Administration (NMPA) named opamtistomig a breakthrough therapy in October 2024, and orphan designations followed from the European Commission in January 2026 and from Japan’s health ministry in September 2026. The NMPA granted priority review to a new drug application in July 2026 and accepted the application in August 2026.⁵ Development now spans 14 indications, among them a single-arm registrational study and a confirmatory phase 3 trial.

“BTC represents a significant unmet medical need, and immunologically cold tumors remain a major challenge for cancer immunotherapy,” Cai stated in the news release.¹

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. Nanjing Leads Biolabs Co., Ltd. October 12, 2026. Accessed October 13, 2026. https://tinyurl.com/9uzbyr5n

2. 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. Nanjing Leads Biolabs Co., Ltd. July 30, 2026. Accessed October 13, 2026. https://tinyurl.com/bdfwhpmd

3. WCLC 2026 | Leads Biolabs’ Opamtistomig (LBL-024) Oral Presentation Demonstrates Robust Response and PFS Benefits in First‑Line NSCLC. News release. Nanjing Leads Biolabs Co., Ltd. September 14, 2026. Accessed October 13, 2026. https://tinyurl.com/58wcyzxz

4. 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

5. Priority Review Granted to PD-L1/4-1BB Bispecific Antibody Opamtistomig, Accelerating Commercialization and Addressing Unmet Need in EP-NEC. News release. Nanjing Leads Biolabs Co., Ltd. July 10, 2026. Accessed October 13, 2026. https://tinyurl.com/322bs8ns