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

Platinum resistant ovarian cancer

39 patients in dose escalation, median 4 prior therapies (1-9); 69% w/ prior bevacizumab, 62% w/ prior PARP inhibitor

Recurrence

Open-Label, Non-randomized

ORR, evaluated per RECIST

Exploratory:
High FRalpha expression: ≥75% of tumor cells staining at ≥2+ intensity per IHC
Low FRalpha expression: ≥ 25% and <75% of tumor cells staining at ≥1+ intensity per IHC

ORR: 34.2% (n=38)

Exploratory analysis, FRalpha levels; dosing above 1.6 mg/kg:
FRalpha high (n=13): ORR: 46.2%
FRalpha high and doses of 1.6 mg/kg or above (n=9): ORR: 55.6%
FRalpha low (n=14): ORR: 35.7%
FRalpha low and doses of 1.6 mg/kg or above (n=12): ORR: 41.7%

Serious AE: overall (15.4%)
Grade 3-4 AE: overall (43.6%), neutropenia (17.9%), anemia (15.4%)

AZD5335 demonstrates a manageable safety profile and preliminary signs of anti-tumor efficacy in platinum resistant ovarian cancer

Shapira-Frommer R et al. 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). Ann Oncol (2024) 35 (2) abstract 754P
https://www.clearityfoundation.org/wp-content/uploads/2024/10/AZD5335-abstract-ESMO-2024.pdf

Shapira-Frommer R et al. Poster
https://www.clearityfoundation.org/wp-content/uploads/2024/10/AZD5335-poster-ESMO-2024.pdf