What question did this study set out to answer?

To evaluate the efficacy of AZD5335, a folate receptor alpha-targeted ADC, in treating lung adenocarcinoma.

April 5, 2026

Abstract 2661: AZD5335, a folate receptor alpha-targeted ADC, exerts anti-tumor responses within lung adenocarcinoma

Key Points

To evaluate the efficacy of AZD5335, a folate receptor alpha-targeted ADC, in treating lung adenocarcinoma.
Utilized a panel of FRα-expressing lung cancer cell lines to assess cytotoxicity of AZD5335.
Correlated in vitro sensitivities of cell lines with FRα expression levels.
Tested AZD5335 in nine patient-derived xenograft models of lung adenocarcinoma (LUAD).
Five out of nine patient-derived xenograft models responded to AZD5335, showing a ≥ 30% reduction in tumor volumes.
Overall response rate was approximately 56%.
Some models exhibited tumor stasis after treatment with AZD5335.

Abstract

Abstract AZD5335 is a folate receptor alpha (FRα)-targeted antibody-drug conjugate (ADC), incorporating a topoisomerase-1 inhibitor (TOP1i) payload. This ADC is currently being developed as a treatment option for FRα-expressing ovarian cancer patients (NCT#05797168-FONTANA). Since FRα has been reported to be expressed in lung adenocarcinoma (LUAD), the purpose of these studies was to pre-clinically evaluate AZD5335 efficacy within LUAD. Employing a panel of FRα-expressing lung cancer cell lines, we demonstrated target-mediated cytotoxicity of AZD5335 and correlated the in vitro sensitivities with FRα expression levels. These studies support ongoing in vivo proof-of-concept studies using cell-derived xenograft models to further define the efficacy and pharmacodynamics of AZD5335. Additional AZD5335 efficacy testing was performed within 9 FRα-expressing patient-derived xenograft (PDX) models of LUAD. Five of these 9 models responded to AZD5335 (2.5mg/kg) and exhibited a ≥ 30% reduction in tumor volumes (ORR ≈ 56%); AZD5335-related tumor stasis occurred in three additional models. These pre-clinical efforts indicated FRα is an actionable target in LUAD and supported expanding clinical assessment of AZD5335 to LUAD in FONTANA. Citation Format: Jason J. Zoeller, Ravinder Tammali, Nancy Lee, Isabella Tilmont, Judith Anderton, Shailesh Metkar, Michael Ophir, Jixin Wang, Claire Myers, Lara McGrath, Alma Andoni, Ina Bisha, Iris Dino, Xhenifer Guza, Simon Christ, Michael Lehmann, Roger Dodd, Neki Patel, Tim Brier, Marc L. Hyer, Marco Gymnopoulos, Sabina Cosulich, Alejandra Negro, Elaine Hurt, Puja Sapra. AZD5335, a folate receptor alpha-targeted ADC, exerts anti-tumor responses within lung adenocarcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2661.

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