Domestic LAG-3 mAb LBL-007 Demonstrates Over 70% Improvement in Median PFS, Enhancing PD-1-Based Combination Therapy

Local TimeMay 30–June 3: The Premier Global Academic Conference in Oncology、AnnualAmerican Society of Clinical Oncology (ASCO Annual Meeting)UpcomingIn ChicagoConvene。Among them, continuous5-Year SelectionASCOdomestically producedImpressive Poster Data for LAG-3 Antibody LBL-007 Demonstrates Potential to Enhance the Efficacy of PD-1 Monoclonal Antibody Plus Chemotherapy, Poised to Become a New Benchmark for First-Line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma (R/M NPC)。

Of greater note, these Phase II data validate that LAG-3 monoclonal antibodies not only enhance the efficacy of PD-1 monoclonal antibodies in the treatment of solid tumors (including improvements in ORR, PFS, and potential OS benefits), but also demonstrate a favorable safety and compliance profile with limited toxicity.From this point forward, LAG3 monoclonal antibodies represented by LBL-007 hold the potential to revolutionize combination therapies for a variety of solid tumors.

As a commercially validated novel target, LAG3 has attracted significant investment from numerous pharmaceutical companies worldwide. According to Frost & Sullivan, as of November 2024, LBL-007 isOne of the top three globally advanced LAG3-targeting monoclonal antibodies in clinical development (excluding the only approved LAG3-targeted therapy), alsoThe first antibody in its class proven effective against nasopharyngeal carcinoma。

For various solid tumors, including nasopharyngeal carcinoma, the combination of immunotherapy (i.e., anti-PD-1 monoclonal antibodies) and chemotherapy has been recommended as the new first-line standard of care due to characteristics such as high PD-L1 expression and substantial infiltration of non-malignant lymphocytes, yielding significant patient benefits. Furthermore, the addition of LAG-3 inhibition appears to further enhance the efficacy of anti-PD-1 monoclonal antibodies.

The Phase II data presented in this poster show that,Patients receiving combination therapy with LBL-007, tislelizumab, and chemotherapy achieved an objective response rate (ORR) of 83.3%,This represents an increase of nearly 20 percentage points compared to the 69.5% observed with tislelizumab plus chemotherapy alone.This indicates that the addition of LBL-007 significantly improved the clinical response rate in recurrent or metastatic nasopharyngeal carcinoma, resulting in tumor shrinkage or stabilization.

A more noteworthy indicator is the significant prolongation of progression-free survival (PFS). In the group receiving combination therapy with LBL-007,Median PFS reached 15.8 months, representing an improvement of over 70% compared to the historical data of 9.6 months for tislelizumab plus chemotherapy, with an extension of more than 6 months.The improved PFS indicates that patients can maintain disease stability for a longer duration and slow disease progression after receiving combination therapy, thereby securing a critical window for treatment while significantly enhancing patients' quality of life and prognosis.

Although the overall survival (OS) data are not yet mature, a trend toward benefit is observed, with the potential to surpass the significant survival benefit demonstrated by the tislelizumab plus chemotherapy regimen.

Furthermore, favorable efficacy has also been observed in patients with esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, and squamous non-small cell lung cancer, suggesting the potential of this therapeutic approach for various solid tumors. Notably, in patients with squamous non-small cell lung cancer, the objective response rate (ORR) of LBL-007 combination therapy reached 25.0%.

Latest Phase II data show,The discontinuation rate in the LBL-007 combination regimen was 4.8%, lower than the historical rate of 5.3% for tislelizumab plus chemotherapy, indicating favorable safety and adherence.

From the perspective of drug design, LBL-007 is a fully human IgG4 monoclonal antibody targeting LAG3. It binds to a unique epitope of LAG3 with high affinity and blocks the interaction between LAG3 and all four identified immunosuppressive ligands. Upon binding to LAG3, LBL-007 induces efficient internalization, downregulates surface expression of LAG3, thereby further blocking ligand interactions and enhancing immune responses. In previously disclosed Phase Ib data, no dose-limiting toxicities (DLTs) were observed during the dose-escalation phase, and the recommended Phase II dose is 400 mg.

As a systemic medical treatment regimen, chemotherapy drugs themselves possess significant systemic toxicity, which may trigger a series of adverse events. Long-term use of chemotherapy can lead to Grade 3 or higher acute toxic reactions, such as acute mucositis and severe hemorrhage.

And from the perspective of this Phase II clinical trial,Despite the use of a four-drug combination regimen, no new safety signals were observed with the addition of LBL-007 compared to tislelizumab plus chemotherapy alone.This indicates that the addition of LBL-007 did not alter the overall safety profile, did not significantly increase additional safety risks, and no new safety issues emerged, demonstrating a manageable safety profile. In other words, the safety risks faced by subjects remain primarily attributable to chemotherapy agents.

The safety and efficacy data disclosed at this year’s ASCO meeting indicate thatThe combination of the LAG3 monoclonal antibody LBL-007 with tislelizumab and chemotherapy has the potential to become the new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma, with prospects for gradual expansion into a broader market of advanced solid tumors, thereby providing more effective therapeutic options for a wide range of cancer patients.

LAG3 is an immune checkpoint receptor on activated T cells. Anti-LAG3 antibodies bind to LAG3, blocking its interaction with ligands, inhibiting signaling pathways, promoting T cell proliferation and cytokine secretion, thereby restoring tumor immune surveillance. Antibodies targeting LAG3 are currently being developed or have been developed for the treatment of various solid tumors.

The combination of LAG3 inhibitors with anti-PD-1/PD-L1 agents has demonstrated significant synergistic potential. This combination therapy more effectively modulates T-cell function, enhances the immune system’s ability to recognize and attack tumors, restores the function of suppressed effector T cells, increases the number of activated CD8+ and CD4+ T cells, and improves their capacity to target tumor cells.Crucially, extensive research has demonstrated that this combination therapy can significantly improve response rates compared to PD-1 monotherapy, thereby addressing the major challenge of PD-1 resistance in cancer treatment.

The FDA-approved, globally first co-approved LAG3-targeting antibody combination, relatlimab plus nivolumab, has already demonstrated the potential of this combination therapy:In March 2022, the FDA approved Opdualag, the first and only LAG-3–targeting antibody combination (relatlimab in combination with the anti-PD-1 antibody nivolumab), for the treatment of unresectable or metastatic melanoma. Compared with the standard regimen of nivolumab monotherapy, the Opdualag regimen more than doubled the median progression-free survival.

In its first full year following commercial launch, Opdualag achieved global sales of $627 million in 2023; sales reached $928 million in 2024, representing a 48% year-on-year increase, placing it just one step away from achieving “blockbuster” drug status.

In preclinical studies, LBL-007 demonstrated superior tumor growth inhibition and efficacy compared to relatlimab, the LAG-3 antibody component of Opdualag. Focusing on the indication of recurrent or metastatic nasopharyngeal carcinoma, the LBL-007 research team is actively advancing pivotal Phase III clinical trials to further validate the advantages of this combination therapy and accelerate the global clinical development and commercialization of LBL-007.

Furthermore, clinical study data demonstrate that LBL-007 in combination with PD-1 inhibitors exhibits robust synergistic antitumor efficacy and a favorable safety profile across multiple tumor types. In addition to advanced nasopharyngeal carcinoma, Phase II clinical trials of the LBL-007 and PD-1 inhibitor combination therapy are underway in China and globally for various solid tumor indications, includingNon-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma.