Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ID: DRG0BIQVN)
ADC Name
Torvutatug samrotecan
Synonyms
torvutatug samrotecan; AZD5335; torvu-sam
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Organization
AstraZeneca (Top20 MNC) (Originator)
Drug Status
Phase 3
Drug-to-Antibody Ratio
8
Structure
Antibody Name
Torvutatug
  Antibody Info 
Antigen Name
Folate receptor alpha (FOLR1)
  Antigen Info 
Payload Name
AZ14170132 (AZ0132)
  Payload Info 
Payload Target
DNA topoisomerase 1 (TOP1)
  Target Info 
Linker Name
Mal-PEG8-Val-Ala
  Linker Info 
Conjugate Type
Random Cysteines
Combination Type
samrotecan
2027 Update
The disease landscape of This ADC
2027 Update
The clinical trial pipelines of This ADC
Indication Phase 1 Phase 2 Phase 3 Approved
Unspecific solid tumor
1 Trials
Trial ID
TWCT00004162; NCT05797168; jRCT2031230175; EudraCT2022-502576-23; EUCT2022-502576-23-00; CTR20240220
Lung cancer
1 Trials
Trial ID
TWCT00004162; NCT05797168; jRCT2031230175; EudraCT2022-502576-23; EUCT2022-502576-23-00; CTR20240220
Peritoneal cancer
1 Trials
Trial ID
TWCT00005366; NCT07218809; jRCT2051250229
Ovarian cancer
1 Trials
Trial ID
TWCT00004162; NCT05797168; jRCT2031230175; EudraCT2022-502576-23; EUCT2022-502576-23-00; CTR20240220
1 Trials
Trial ID
TWCT00005366; NCT07218809; jRCT2051250229
Fallopian tube cancer
1 Trials
Trial ID
TWCT00005366; NCT07218809; jRCT2051250229
Endometrial cancer
1 Trials
Trial ID
TWCT00004162; NCT05797168; jRCT2031230175; EudraCT2022-502576-23; EUCT2022-502576-23-00; CTR20240220
2027 Update
ADC-specific functional property
Bystander Killing Effect
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Bystander Killing Effect Description Reference
yes
AZD5335's primary mechanism of action is to deliver TOP1i payload into FRalpha-expressing cancer cells, leading to DNA damage and apoptotic cell death. The TOP1i payload mediates bystander killing, which is important for targeting tumors with less than uniformly positive expression.

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[1]
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  NCT05797168
PHASE1|||PHASE2
A Modular Phase I/IIa, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD5335 Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors

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Undisclosed  NCT05797168
Phase 1/2
FONTANA: A modular phase 1/2a, open-label, multi-center study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of ascending doses of AZD5335 monotherapy and in combination with anti-cancer agents in participants with solid tumors.

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Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Eligible participants ≥18 years have advanced solid tumors, measurable disease (RECIST v1.1), ECOG 0-1, and adequate organ function. Exclusions: uncontrolled infections (HBV/HCV/HIV), active ILD, significant cardiac disease (QTc >470 ms, heart failure), recent cancer (except cured malignancies), or pregnancy. Contraception is mandated. Prior therapies must meet washout criteria.

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Administration Dosage
Pts aged ≥18 years with PRROC were recruited irrespective of tumour FRalpha expression and without a limit on the number of prior lines of therapy. AZD5335 was administered intravenously Q3W until disease progression, unacceptable toxicity, or other reason for discontinuation.
Related Clinical Trial
NCT Number NCT05797168  Clinical Status PHASE1|||PHASE2
Clinical Description A Modular Phase I/IIa, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD5335 Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors
Primary Endpoint
The study assesses the safety and tolerability of AZD5335/AZD5305 by monitoring adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) per NCI CTCAE v5.0, including lab abnormalities, vital signs, and ECGs.
Other Endpoint
Efficacy is evaluated via RECIST v1.1, measuring ORR (CR/PR), DCR (CR/PR/SD ≥15 weeks), DoR, PFS, and OS. PK parameters (AUC, Cmax, Tmax, clearance, t1/2) are analyzed for AZD5335 alone or combined with AZD5305/bevacizumab/carboplatin. Immunogenicity (ADA development) and tumor target expression changes are also assessed.
Experiment 2 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT05797168  Clinical Status Phase 1/2
Clinical Description FONTANA: A modular phase 1/2a, open-label, multi-center study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of ascending doses of AZD5335 monotherapy and in combination with anti-cancer agents in participants with solid tumors.
Primary Endpoint
Number of participants with adverse events/serious adverse events, the number of participants with dose limiting toxicity (DLT).
Other Endpoint
Objective Response Rate (ORR), Duration of Response (DoR), Disease Control Rate (DCR), Progression free Survival (PFS), Overall Survival (OS).
References
Ref 1 First disclosure of AZD5335, a TOP1i-ADC targeting low and high FR-expressing ovarian cancer with superior preclinical activity vs FR-MTI ADC. Cancer Res (2023) 83 (8_Supplement): LB025.
Ref 2 Phase I/IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors
Ref 3 FONTANA: A Modular Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Ascending Doses of AZD5335 Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors, NCT05797168