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FRα TOPO1i ADC

Compound Torvutatug samrotecan (AZD5335)

Area under investigation

Advanced solid tumors

Scientific PillarAntibody-Drug Conjugates

 

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FONTANA trial overview

Tumor

Advanced solid tumors

Trial Identifier

NCT05797168

Phase

I/IIa

Regimen

Torvutatug samrotecan monotherapy; torvutatug samrotecan + saruparib; torvutatug samrotecan + bevacizumab; torvutatug samrotecan + carboplatin ± bevacizumab; torvutatug samrotecan + palacaparib

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FONTANA trial overview

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Target Overview

FRα is a cell surface protein that binds and internalizes folate, a cofactor required for DNA synthesis, cell growth, and proliferation. Normal adult tissues generally lack FRα expression. In contrast, FRα is highly expressed in multiple epithelial tumors, including ovarian cancer and lung adenocarcinoma.1-4

Compound Overview

Torvutatug samrotecan (AZD5335) is a specific, targeted antibody-drug conjugate that binds with high affinity to FRα and delivers a potent topoisomerase 1 inhibitor (TOP1i) payload across a broad range of FRα expression levels. Upon internalization and trafficking to the lysosome, the TOP1i payload is released into the cell where it traps TOP1 on DNA, ultimately resulting in tumor cell death. The TOP1i payload can also diffuse through the cell membrane to exert bystander anti-tumor activity. Torvutatug samrotecan is currently under investigation as a monotherapy and in combination with other therapeutic agents.5,6

Mechanism of Action

  • Mechanism of Action

References

1. Weitman SD et al. Cancer res. 1992;52(12):3396-3401. 2. Mantovani L et al. Eur J of Cancer. 1994;30(3):363369. 3. Kelemen LE et al. Int J Cancer. 2006;119(2):243250. 4. Elnakat H et al. Adv drug deliv rev. 2004;56(8):10671084. 5. Zoeller JJ et al. Clin Cancer Res. 2025;31(24):5261-5275. 6. Oaknin A. Presented at ESMO; October 17-21, 2025; Berlin, Germany. Abstract: 1065MO.

 

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FONTANA trial overview

Tumor

Advanced solid tumors

Trial Identifier

NCT05797168

Phase

I/IIa

Regimen

Torvutatug samrotecan monotherapy; torvutatug samrotecan + saruparib; torvutatug samrotecan + bevacizumab; torvutatug samrotecan + carboplatin ± bevacizumab; torvutatug samrotecan + palacaparib

Visit ct.gov

FONTANA Overview Modal

FONTANA trial overview

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Abbreviations

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  • DNA

    deoxyribonucleic acid

  • FRα

    folate receptor α

  • NSCLC

    non-small cell lung cancer

  • TOP1i

    topoisomerase 1 inhibitor

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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