Light Chain Bioscience Reports Promising Survival Data for NI-1801 Bispecific Antibody in Platinum-Resistant Ovarian Cancer
核心洞察
Light Chain Bioscience (搜索) presented positive Phase 1/1b results for NI-1801, a first-in-class mesothelin x CD47 (搜索) bispecific antibody, showing a 75.2% one-year overall survival rate when combined with pembrolizumab in heavily pretreated platinum-resistant ovarian cancer (搜索) patients.
The combination therapy demonstrated a 28.5% confirmed response rate and 48% clinical benefit rate in patients who had received at least four prior chemotherapy lines, representing the most challenging ovarian cancer (搜索) subpopulation.
NI-1801 was well tolerated both as monotherapy and in combination with pembrolizumab, offering a chemotherapy-free treatment approach that engages both innate and adaptive immune pathways.
Light Chain Bioscience (搜索) presented compelling clinical data for its lead bispecific antibody NI-1801 at the 2025 European Society of Medical Oncology (ESMO) Congress, demonstrating significant survival benefits in heavily pretreated platinum-resistant ovarian cancer (搜索) patients. The Phase 1/1b study results showed a one-year overall survival rate of 75.2% when NI-1801 was combined with pembrolizumab, marking a potential breakthrough in treating one of oncology's most challenging patient populations.
Clinical Trial Results Show Strong Survival Signal
The Phase 1b combination study evaluated NI-1801 plus pembrolizumab in 21 patients with platinum-resistant ovarian cancer (搜索) who had received at least four prior chemotherapy lines. At the August 2025 data cutoff, with a median follow-up of 11 months, 15 patients remained alive with six patients still ongoing treatment. The combination achieved a confirmed response rate of 28.5% by RECIST criteria and a clinical benefit rate of 48%.
The immature progression-free survival rate reached 32.7% at nine months. In comparison, the monotherapy Phase 1 study of NI-1801 showed a one-year overall survival rate of 35.3% in 21 patients, with a median follow-up of 19 months and seven patients alive at data cutoff.
Novel Mechanism Targets Dual Immune Pathways
NI-1801 represents a first-in-class mesothelin x CD47 (搜索) bispecific antibody that selectively targets the innate immune checkpoint CD47 on mesothelin-expressing cancer cells. This dual-targeting approach addresses both innate and adaptive immune pathways, potentially overcoming the immunosuppressive barriers that have historically limited immunotherapy success in ovarian cancer (搜索).
"These findings support a therapeutic strategy that synergistically engages both innate and adaptive immune pathways - by targeting CD47 (搜索) within the tumor microenvironment and blocking the PD-L1 (搜索)/PD-1 (搜索) axis - as a promising chemotherapy-free approach to enhance immunotherapy efficacy," said Professor Thibault de la Motte Rouge, Research Director at Centre Eugène Marquis, France, who presented the data at ESMO.
Addressing Critical Unmet Medical Need
The study population represents the most fragile subpopulation of ovarian cancer (搜索) patients, having received at least four prior chemotherapy lines. Previous studies have reported median overall survival ranging from 9 to 12 months with standard of care chemotherapy in platinum-resistant ovarian cancer (搜索) patients who received at least one chemotherapy line.
"Patients with platinum-resistant ovarian cancer (搜索) face poor survival outcomes, and current treatment options remain limited, highlighting the urgent need for novel therapeutic approaches," noted Professor de la Motte Rouge. "To date, clinical results with immunotherapy in ovarian cancer (搜索) have been largely disappointing, although the recent Phase III Keynote-B96 trial has shown a benefit with pembrolizumab in patients with early relapsing platinum-resistant disease."
Safety Profile Supports Continued Development
NI-1801 demonstrated a favorable safety and tolerability profile both as monotherapy and in combination with pembrolizumab. The treatment was well tolerated across both study arms, supporting its potential as a chemotherapy-free therapeutic option.
Dr. Jose Saro, Chief Medical Officer of Light Chain Bioscience (搜索), emphasized the clinical significance: "The overall survival rate reported for NI-1801 in combination with pembrolizumab is particularly noteworthy in a chemotherapy-free regimen, and it is the first example of a combined immunotherapy approach to show effectiveness in this hard-to-treat ovarian cancer (搜索) patient population."
Broader Implications for CD47-Targeted Therapy
The positive results provide validation for Light Chain Bioscience (搜索)'s approach to CD47 (搜索) targeting through bispecific antibodies rather than monoclonal antibodies. CEO Nicolas Fischer noted that these findings "confirm our long-held conviction that bispecific antibodies targeting CD47 have a fundamentally different therapeutic window than anti-CD47 monoclonal antibodies, which have faced major setbacks."
The company is advancing NI-1801 through multiple clinical trials, including a Phase 2 randomized trial in platinum-resistant ovarian cancer (搜索) patients who have received 1-3 prior chemotherapy lines. Light Chain Bioscience (搜索), based in Geneva, Switzerland, leverages its proprietary κλ body platform to design fully human IgG bispecifics with selective biological activity.
Ovarian cancer (搜索) accounts for approximately 200,000 deaths worldwide annually and represents a heterogeneous disease with major differences in incidence, tumor behavior, and outcomes across histological subtypes. Treatment options for platinum-resistant recurrence cases remain limited, with no effective therapies that significantly prolong prognosis, making NI-1801's clinical profile particularly noteworthy for this patient population.