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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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TREVI-OC-01 trial overview

Tumor

High-grade, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer expressing high or low FRα levels

Trial Identifier

NCT07218809

Phase

III

Regimen

Torvutatug samrotecan vs. mirvetuximab soravtansine in FRα-high and torvutatug samrotecan vs. chemotherapy in FRα-low platinum-resistant ovarian cancer 

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria are –

  • Age ≥18 years
  • Confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer
  • Platinum-resistant disease: Participants who have only had one prior line of platinum-based therapy must have received ≥4 cycles of platinum, must have had CR or PR and then progressed 3-6 months after the date of the last dose of platinum. Participants with 2 or 3 lines of platinum therapy must have progressed ≤6 months after the date of the last dose of platinum
  • Radiological progression on or after most recent line of therapy
  • Must have received at least one but no more than 3 prior systemic lines of anti-cancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment
  • Participants with documented BRCA mutation (germline and/or somatic) must have received prior PARPi if eligible per approved label and SoC institutional guidelines, except in cases of documented contraindication, precaution or intolerance
  • Provision of an FFPE tumor tissue sample

 

Reference:

Study NCT07218809. ClinicalTrials.gov website. 

 

Exclusion criteria

 

The key exclusion criteria are –

  • Endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade or borderline ovarian tumor
  • Primary platinum-refractory disease, defined as disease that did not respond to or has progressed ≤3 months after the last dose of first line platinum-containing chemotherapy
  • Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring
  • Current signs, symptoms, or clinical investigations consistent with bowel obstruction, including sub-occlusive disease
  • Non-infectious ILD/pneumonitis or history of non-infectious ILD/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • Prior treatment with any FRα-targeted therapy, including MIRV, or any TOP1i ADC
  • Major surgical procedure within 4 weeks of the first dose of study intervention

TREVI-OC-1 Overview Modal

TREVI-OC-1 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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TREVI-OC-01 trial overview

Tumor

High-grade, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer expressing high or low FRα levels

Trial Identifier

NCT07218809

Phase

III

Regimen

Torvutatug samrotecan vs. mirvetuximab soravtansine in FRα-high and torvutatug samrotecan vs. chemotherapy in FRα-low platinum-resistant ovarian cancer 

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria are –

  • Age ≥18 years
  • Confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer
  • Platinum-resistant disease: Participants who have only had one prior line of platinum-based therapy must have received ≥4 cycles of platinum, must have had CR or PR and then progressed 3-6 months after the date of the last dose of platinum. Participants with 2 or 3 lines of platinum therapy must have progressed ≤6 months after the date of the last dose of platinum
  • Radiological progression on or after most recent line of therapy
  • Must have received at least one but no more than 3 prior systemic lines of anti-cancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment
  • Participants with documented BRCA mutation (germline and/or somatic) must have received prior PARPi if eligible per approved label and SoC institutional guidelines, except in cases of documented contraindication, precaution or intolerance
  • Provision of an FFPE tumor tissue sample

 

Reference:

Study NCT07218809. ClinicalTrials.gov website. 

 

Exclusion criteria

 

The key exclusion criteria are –

  • Endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade or borderline ovarian tumor
  • Primary platinum-refractory disease, defined as disease that did not respond to or has progressed ≤3 months after the last dose of first line platinum-containing chemotherapy
  • Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring
  • Current signs, symptoms, or clinical investigations consistent with bowel obstruction, including sub-occlusive disease
  • Non-infectious ILD/pneumonitis or history of non-infectious ILD/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • Prior treatment with any FRα-targeted therapy, including MIRV, or any TOP1i ADC
  • Major surgical procedure within 4 weeks of the first dose of study intervention

TREVI-OC-1 Overview Modal

TREVI-OC-1 trial overview

Take me to ClinicalTrials.Gov

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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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