The Anti-FRα Antibody–Drug Conjugate Luveltamab Tazevibulin Demonstrates Efficacy in Non–Small Cell Lung Cancer Preclinical Models - Summary of Findings

Sep 23, 2026

Uploaded by Mimi

Luveltamab tazevibulin is a folate receptor α (FRα)–targeting antibody–drug conjugate evaluated as a potential treatment for non–small cell lung cancer using preclinical models enriched for FRα expression. In patient-derived xenografts, FRα-expressing tumors showed robust tumor growth inhibition after treatment. The ADC also induced immunogenic cell death, activating hallmarks including HMGB1 and ATP release and calreticulin surface exposure, and generated protective vaccination effects against later tumor challenge. It further reshaped tumor immune infiltration and enhanced efficacy when combined with immune checkpoint blockade, linked to increased CD8+ T-cell presence.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Introduction

FRα as a therapeutic target

Clinical and preclinical context of FRα-directed ADCs

Preclinical efficacy and immunogenic cell death

The Anti-FRα Antibody–Drug Conjugate Luveltamab Tazevibulin Demonstrates Efficacy in Non–Small Cell Lung Cancer Preclinical Models and Induces Immunogenic Cell Death Robert Yuan, Andrew McGeehan, Sihong Zhou, Christine Cheng, Mark Armanini, Jennifer Smith, Millicent Embry, Rhoneil Pena, Danielle K. Lewis, Genevive Hernandez, Krishna Bajjuri, Cuong Tran, Gang Yin, Cristina Abrahams, Xiaofan Li, Hans-Peter Gerber, Alice Yam, and Helena Kiefel | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Luveltamab tazevibulin is a folate receptor α (FRα)–targeting antibody–drug conjugate currently being evaluated in phase I and II/III clinical trials in endometrial and ovarian cancers (NCT03748186 and NCT05870748), respectively. In this study, wereport non–small cell lung cancer (NSCLC) as an additional cancer subtype enriched for FRα expression. In patient-derived xenograft models of NSCLC, FRα-expressing tumors demonstrated robust tumor growth inhibition following luveltamab tazevibulin treatment, demonstrating its potential use for NSCLC treatment. Luveltamabtazevibulin was additionally identified as a potent inducer of immunogenic cell death (ICD). In in vitro cell killing assays, luveltamabtazevibulin induced all three hallmarks of ICD—high mobility group box 1 release, ATP release, and surface exposure of calreticulin. Furthermore, in in vivo vaccination studies, injection of luveltamabtazevibulin–treated tumor cells established protective immunity
􀀶 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | against subsequent tumor challenge. Consistent with ICD induction, luveltamab tazevibulin treatment in tumor-bearing mice also altered tumor immune cell infiltrate and activation, demonstrating its ability to modulate the tumor immune microenvironment. Given the success of immune checkpoint therapy in NSCLC and luveltamabtazevibulin’s ability to potentiate the immune response, we evaluated the combination therapy of luveltamab tazevibulin with immune checkpoint blockade in syngeneic mouse models and demonstrated that combination treatment results in enhanced efficacy compared with either monotherapy alone. This improved activity with combination therapy was associated with increased tumoral infiltration of CD8+ T cells. In conclusion, the work presented here provides rationale for evaluating luveltamab tazevibulin in NSCLC either as monotherapy or in combination with immune checkpoint blockade. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Introduction Folate receptor α (FRα) is a single-chain glycosylphosphatidylinositolanchored membrane glycoprotein that plays a critical role in transporting folate into cells (1). In oncology, FRα has garnered substantial interest for targeted therapy because of its restricted expression pattern in normal cells and its overexpression in multiple cancers, such as ovarian cancer, endometrial cancer, non–small cell lung cancer (NSCLC), and triplenegati

FAQs

How was FRα enrichment used to evaluate luveltamab tazevibulin in NSCLC models?

The study evaluated non–small cell lung cancer as an additional subtype enriched for FRα expression, using patient-derived xenograft models to observe treatment effects in FRα-expressing tumors.

What immunogenic cell death markers did luveltamab tazevibulin induce?

In vitro assays showed induction of all three hallmark ICD features: HMGB1 release, ATP release, and calreticulin surface exposure.

Why is combination therapy with immune checkpoint blockade important in this work?

Because immune checkpoint therapy has shown success in NSCLC and luveltamab tazevibulin can potentiate immune responses, the study tested combination treatment and observed enhanced efficacy over either monotherapy, associated with increased CD8+ T-cell infiltration.

Sep 23, 2026

Uploaded by Mimi