torvutatug samrotecan (AZD5335) / AstraZeneca - LARVOL DELTA

TREVI-OC-03: Torvutatug Samrotecan With or Without Bevacizumab as Maintenance Treatment of Platinum-sensitive Relapsed Epithelial Ovarian Cancer (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Platinum sensitive • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Updated results from FONTANA: Torvutatug samrotecan (torvu-sam), a folate receptor α (FRα)-targeted antibody-drug conjugate (ADC), in patients (pts) with platinum-resistant ovarian cancer (PROC) (ESMO 2026) - No abstract available

ADC • Clinical • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

First-in-human study of AZD5335, a folate receptor α (FRα)-targeted antibody-drug conjugate, in patients with platinum-resistant recurrent ovarian cancer (ESMO 2025) - P1/2 | "Conclusions AZD5335 is associated with a manageable safety profile and has demonstrated competitive efficacy across all dose levels selected for dose optimization and in both high and low FRα-expressing tumours. Data from this trial will inform future monotherapy and combination opportunities in ovarian and additional solid tumours."

Clinical • First-in-human • P1 data • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Initial results from a first-in-human study of AZD5335, a folate receptor α (FRα)-targeted antibody-drug conjugate, in patients (pts) with platinum-resistant recurrent ovarian cancer (PRROC) (ESMO 2024) - P1/2 | "AZD5335 demonstrated a manageable safety profile and preliminary signs of efficacy. Dose optimisation is underway in module M1B. Ronnie Shapiro-Frommer and Kazuki Sudo have contributed equally to the study."

Clinical • P1 data • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice. (PubMed, Int J Biol Sci) - "AZD5335, a recent clinically tested FRα-targeted antibody-drug conjugate carrying a topoisomerase I inhibitor payload, exceeded its predecessors by demonstrating remarkable efficacy against low FRα-expressing tumors as well. Thus, FRs emerge as selective and promising targets for advanced precision oncology of various malignancies including those displaying chemoresistance."

Journal • Review • Oncology • FOLR1

FONTANA: Phase I/IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors (clinicaltrials.gov) - P1/2 | N=602 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jan 2028 ➔ Aug 2028 | Trial primary completion date: Jan 2028 ➔ Aug 2028

Monotherapy • Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma

Torvutatug samrotecan: Data from P3 Trevi-OC-01 trial (NCT07218809) for d FRα platinum resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer post 2027 (AstraZeneca) - H1 & Q2 2026 Results: Data from P1/2 FONATANA trial (NCT05797168) for solid tumors post 2027

P1/2 data • P3 data • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

MODULE 2: Strategies Targeting Folate Receptor Alpha (FRα) in Advanced OC (ASCO 2026) - "Supported by This activity is supported by educational grants from AbbVie Inc, AstraZeneca Pharmaceuticals LP, Corcept Therapeutics Inc, and Merck. Incidence and clinical relevance of FRα expression in OC; optimal approaches to and timing of FRα testingLong-term data, including OS findings, with mirvetuximab soravtansine for patients with FRα-positive, platinum-resistant OC from the Phase III MIRASOL trial; optimal integration into current management algorithmsKey findings from the Phase II PICCOLO trial of mirvetuximab soravtansine for FRα-positive, platinum-sensitive OC; current and potential clinical roleDesign, eligibility criteria and primary and secondary endpoints of the Phase III GLORIOSA trial evaluating mirvetuximab soravtansine in combination with bevacizumab versus bevacizumab alone as maintenance therapy for patients with FRα-positive OC who have not experienced disease progression after second-line platinum-based chemotherapy and bevacizumabMechanistic..."

Metastases • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

TREVI-OC-01: AZD5335 vs. Mirvetuximab Soravtansine in FR?-high and AZD5335 vs. Chemotherapy in FR?-low Platinum-resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=1100 | Recruiting | Sponsor: AstraZeneca | Trial completion date: May 2030 ➔ Dec 2029

Platinum resistant • Trial completion date • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

TREVI-OC-01: AZD5335 vs. Mirvetuximab Soravtansine in FRα-high and AZD5335 vs. Chemotherapy in FRα-low Platinum-resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=1100 | Recruiting | Sponsor: AstraZeneca | N=309 ➔ 1100

Enrollment change • Platinum resistant • Trial initiation date • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

AZD5335, a folate receptor alpha-targeted ADC, exerts anti-tumor responses within lung adenocarcinoma (AACR 2026) - "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."

ADC • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

AstraZeneca…registered a Phase III clinical trial (Registration No.: CTR20261196) for AZD5335 in treating platinum-resistant high-grade epithelial ovarian cancer patients with folate receptor alpha (FRα) positivity (high expression and low expression) after 1-3 lines of treatment (FUTU) - "This marks the initiation of the domestic clinical portion of the TREVI-OC-01 study. TREVI-OC-01 is a randomized, open-label, Phase III study designed to evaluate the efficacy and safety of AZD5335 compared to standard of care (SoC) in subjects with platinum-resistant recurrent ovarian cancer who have previously received 1-3 systemic treatment regimens, including cohorts with high FRα expression and low FRα expression. In the high FRα expression cohort, AZD5335 is compared to mirvetuximab soravtansine, while in the low FRα expression cohort, it is compared to investigator-selected chemotherapy."

Platinum resistant • Trial status • Epithelial Ovarian Cancer

AZD5335, a folate receptor alpha-targeted ADC, enhances ovarian cancer treatment with bevacizumab, paclitaxel and/or carboplatin (AACR 2025) - "AZD5335, an FRα-targeting antibody conjugated to a topoisomerase 1 inhibitor (TOP1i) payload, is currently being investigated in the FONTANA Phase I/IIa clinical trial (NCT#05797168), either as a single agent or in combination with a PARP1-selective inhibitor (saruparib). A series of in vitro studies will also define the ADC/SOC drug interactions and further delineate underlying mechanisms driving enhanced efficacy. These studies inform our ongoing clinical development of AZD5335 in ovarian cancer."

ADC • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Synergistic antitumor effect of FRα TOP1i antibody drug conjugate, AZD5335, in combination with the PARP1 inhibitor, saruparib (AZD5305), in preclinical models of ovarian cancer (AACR 2024) - P1/2 | "2022, NEJM Evid 2022; 1(9) DOI: 10.1056/EVIDoa22000432. Malanga and Althaus 2004, JBC 2004; 279(7) DOI: 10.1074/jbc.C3004372003."

ADC • Combination therapy • Late-breaking abstract • Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1 • GPI • HRD • TOP1

TREVI-OC-01: AZD5335 vs. Mirvetuximab Soravtansine in FRα-high and AZD5335 vs. Chemotherapy in FRα-low Platinum-resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=289 | Recruiting | Sponsor: AstraZeneca | N=46 ➔ 289

Enrollment change • Platinum resistant • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

D8991C00001: AZD5335 vs. Mirvetuximab Soravtansine in FR?-high and AZD5335 vs. Chemotherapy in FR?-low Platinum-resistant Ovarian Cancer (TREVI-OC-01) (clinicaltrialsregister.eu) - P2/3 | N=46 | Not yet recruiting | Sponsor: AstraZeneca AB

New P2/3 trial • Platinum resistant • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Torvutatug samrotecan (AZD5335) vs mirvetuximab soravtansine gynx in high FRα expressing tumors and torvutatug samrotecan vs chemotherapy in low FRα expressing tumors in patients with platinum resistant epithelial ovarian cancer in the randomized Phase III TREVI OC 01/GOG 3127/ENGOT ov93 trial (SGO 2026) - No abstract available

Clinical • P3 data • Platinum resistant • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

D8991C00002: A trial to learn how safe AZD5335 is and if a drug called itraconazole changes how AZD5335 moves through the body over time in adults with ovarian, peritoneal, or fallopian tube cancer (clinicaltrialsregister.eu) - P1 | N=34 | Recruiting | Sponsor: AstraZeneca AB

New P1 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Drug-drug Interaction Study With AZD5335 and Itraconazole in Participants With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: AstraZeneca

New P1 trial • Platinum resistant • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor

Torvutatug samrotecan: Data from P3 Trevi-OC-01 trial (NCT07218809) for d FRα platinum resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer post 2027 (AstraZeneca) - FY 2025 Resuts: Data from P1/2 FONATANA trial (NCT05797168) for solid tumors post 2027

P1/2 data • P3 data • Platinum resistant • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

TREVI-OC-01: AZD5335 vs. Mirvetuximab Soravtansine in FRα-high and AZD5335 vs. Chemotherapy in FRα-low Platinum-resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=1100 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

AZD5335: Data from P1/2 trial (NCT05797168) for solid tumors post 2026 (AstraZeneca) - Q3 2025 Results

P1/2 data • Oncology • Solid Tumor

AstraZeneca advances its ambition to redefine cancer care with new data across its diverse, industry-leading portfolio and pipeline at the European Society for Medical Oncology (ESMO) Congress, October 17-21, 2025. (AstraZeneca Press Release)

Clinical data • Platinum resistant • pMMR • Tumor mutational burden • Castration-Resistant Prostate Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Hormone Sensitive Prostate Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Triple Negative Breast Cancer

TREVI-OC-01: AZD5335 vs. Mirvetuximab Soravtansine in FRα-high and AZD5335 vs. Chemotherapy in FRα-low Platinum-resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=1100 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Platinum resistant • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

Derivation of AZD5335, a novel FRα-targeted TOP1i-loaded ADC, for the treatment of FRα-expressing cancers. (PubMed, Clin Cancer Res) - "AZD5335 is a promising next-generation ADC capable of targeting ovarian cancers with both high and low FRα expression. AZD5335 demonstrates efficacy in overcoming Elahere-resistance and supports combined treatment strategies."

Journal • Oncology • Ovarian Cancer • Solid Tumor • FOLR1