What type of study is this?

This is a Pre-Registered Trial study.

What question did this study set out to answer?

This study aims to assess the efficacy and safety of combining LBL-007 with tislelizumab and chemotherapy in treating advanced esophageal squamous cell carcinoma.

January 14, 2026

A phase 2 study of LBL-007 (anti-LAG-3) plus tislelizumab (anti-PD-1) and chemotherapy as first-line treatment in patients with unresectable locally advanced/metastatic esophageal squamous cell carcinoma.

Key Points

This study aims to assess the efficacy and safety of combining LBL-007 with tislelizumab and chemotherapy in treating advanced esophageal squamous cell carcinoma.
Phase 2, randomized, active-controlled, open-label trial
Patients aged 18 years and older without prior systemic therapy
Randomized 2:1 to receive LBL-007 + tislelizumab + chemotherapy or tislelizumab + chemotherapy
Primary endpoint was overall response rate (ORR) assessed by RECIST v1.1
Secondary endpoints included progression-free survival (PFS) and treatment-emergent adverse events (TEAEs)
Confirmed ORR was 61.5% in the LBL-007 arm and 60.0% in the control arm
Median PFS was 8.2 months in the LBL-007 arm and 6.9 months in the control arm
Common TEAEs included anemia and decreased neutrophil and white blood cell counts
A significant proportion of patients in both arms experienced grade ≥3 treatment-related TEAEs
Immune-mediated adverse events occurred in about half of the patients in both treatment groups

Abstract

368 Background: Co-inhibition of lymphocyte activation gene-3 (LAG-3) and programmed cell death protein-1 (PD-1) may enhance antitumor responses for patients (pts) with advanced/metastatic esophageal squamous cell carcinoma (ESCC). We evaluated the efficacy and safety of LBL-007, a novel, fully human anti-LAG-3 IgG4 monoclonal antibody (mAb), with tislelizumab (TIS), a humanized IgG4 anti-PD-1 mAb, and chemotherapy (CT) in pts with unresectable, locally advanced/metastatic ESCC, regardless of baseline PD-L1 status. Methods: In this phase 2, randomized, active-controlled, open-label trial (NCT06010303), pts ≥18 years with ECOG PS ≤1 and no prior systemic therapy were randomized 2:1 to LBL-007 (600 mg IV Q3W) + TIS (200 mg IV Q3W) + CT (Arm A; A) or TIS (200 mg IV Q3W) + CT (Arm B; B); CT was 60-80 mg/m 2 cisplatin + 750-800 mg/m 2 5-FU or 175 mg/m 2 paclitaxel IV Q3W. Primary endpoint was overall response rate (ORR) per investigator-assessed RECIST v1.1. Secondary endpoints were progression-free survival (PFS), duration of response (DoR), disease control rate (DCR), and incidence and severity of treatment-emergent adverse events (TEAEs). Results: As of May 30, 2025, 118 pts were randomized (A: n=78; B: n=40). Median age (range) was 61.5 (44-80) years in A and 65.5 (46-80) in B; 85.9% of pts in A and 87.5% in B were male. Median follow-up (range) was 12.5 (0-18.5) months (mo) in A and 11.5 (0.4-18.8) in B. Confirmed ORR (95% CI) was 61.5% (49.8-72.3) in A and 60.0% (43.3-75.1) in B (Table). Median PFS (95% CI) was 8.2 (5.7-9.2) mo in A and 6.9 (5.6-8.2) in B (HR, 0.85 95% CI, 0.54-1.34; P =0.4753). The most common TEAEs were anemia (A: 63 81.8%; B: 27 67.5%), neutrophil count decreased (A: 53 68.8%; B: 24 60.0%) and WBC count decreased (A: 48 62.3%; B: 21 52.5%). Grade ≥3 treatment-related TEAEs occurred in 77.9% of pts in A and 65.0% in B. TEAEs led to discontinuation in 23 (29.9%) pts in A and 11 (27.5%) in B, and to death in 2 (2.6%) and 2 (5.0%) pts, respectively. Immune-mediated AEs occurred in 40 (51.9%) pts in A and 20 (50%) in B, and infusion-related reactions in 7 (9.1%) and 2 (5.0%) pts, respectively. Conclusions: In pts with advanced/metastatic ESCC, adding LBL-007 to TIS + CT did not improve ORR versus TIS + CT alone, which was consistent with historical data in this population. PFS was numerically longer with LBL-007 but not statistically significant. The safety profile of the triplet was manageable and consistent with the known profiles of the individual agents. Clinical trial information: NCT06010303 . Efficacy. Arm An=78 Arm Bn=40 ORR, n (%)95% CI 48 (61.5)49.8-72.3 24 (60.0)43.3-75.1 Complete response 2 (2.6) 1 (2.5) Partial response 46 (59.0) 23 (57.5) Stable disease 23 (29.5) 12 (30.0) Progressive disease 4 (5.1) 3 (7.5) Not evaluable (NE) 3 (3.8) 1 (2.5) DCR, n (%)95% CI 71 (91.0)82.4-96.3 36 (90.0)76.3-97.2 DoR, median, mo95% CI 7.25.7-12.3 7.34.1-NE

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