AZD5335 / AstraZeneca - LARVOL DELTA

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."

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

FONTANA: Phase I/IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors (clinicaltrials.gov) - P1/2 | N=396 | Recruiting | Sponsor: AstraZeneca | N=150 ➔ 396

Enrollment change • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

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

AZD5335: “AZD5335 - differentiated efficacy in heavily pre-treated patients with platinum-resistant relapsed ovarian cancer”; Ovarian cancer (AstraZeneca) - ESMO 2024: “Overall ORR of 34.2% with responses observed at all doses”

P1/2 data • Oncology • Ovarian Cancer

AstraZeneca steps out from Daiichi's shadow, posting data on in-house rivals to AbbVie... (FierceBiotech) - P1/2a | N=150 | NCT05797168 | Sponsor: AstraZeneca | "The poster features data on 39 ovarian cancer patients who received one of five doses of AZD5335. In the 38 dosed patients with an available on-treatment scan at data cutoff, AstraZeneca reported a 34.2% response rate. The response rate was 46.2% in participants with high FRα and 35.7% in patients with low FRα. Excluding the lowest dose boosted the response rates to 55.6% and 41.7%, respectively...The cohorts are small—there were nine people in the analysis that yielded the 41.7% response rate—but there are early signs AZD5335 may be competitive."

P1/2 data • Ovarian Cancer

AstraZeneca advances ambition to improve standards of care in multiple cancer types at WCLC and ESMO 2024 (AstraZeneca Press Release) - "AstraZeneca advances its ambition to revolutionise cancer care with new data across its diverse, industry-leading portfolio and pipeline at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer, 7 to 10 September 2024 and the European Society for Medical Oncology (ESMO) Congress, 13 to 17 September 2024. Across the two meetings, more than 130 abstracts will feature 17 approved and potential new medicines from AstraZeneca including five Presidential Symposia and 41 oral presentations."

Late-breaking abstract • P1/2 data • P2 data • P3 data • Bladder Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor

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."

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

AZD5335: Data from P1/2 FONTANA trial (NCT05797168) for advanced solid tumors post 2025 (AstraZeneca) - Q4 & FY2023 Results

P1/2 data • Oncology • Solid Tumor

FONTANA: A phase I/IIa study of AZD5335 as monotherapy and in combination with anti-cancer agents in patients with solid tumours (ESMO 2023) - P1/2 | "The study will evaluate AZD5335 as monotherapy in patients with ovarian cancer or lung adenocarcinoma (Module 1), or AZD5335 in combination with AZD5305, a selective poly(ADP-ribose) polymerase 1 inhibitor, in patients with ovarian cancer (Module 2). Secondary objectives include assessment of objective response rate, duration of response, disease control rate, and progression-free survival by RECIST v1.1, and overall survival; characterising the pharmacokinetics of AZD5335 when given as monotherapy or in combination; and assessing immunogenicity. The study will be open to recruitment by 25 May 2023."

Clinical • Combination therapy • Monotherapy • P1/2 data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1 • TOP1

FONTANA: Phase I/IIa Study for AZD5335 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • MUC16

"AZD5335 $AZN" (@JacobPlieth)

First disclosure of AZD5335, a TOP1i-ADC targeting low and high FRα-expressing ovarian cancer with superior preclinical activity vs FRα-MTI ADC (AACR 2023) - "Furthermore, AZD5335 demonstrated superior activity vs an FRα-MTI benchmark ADC with respect to anti-tumor activity and duration of response in two PDX models with low-to-medium FRα expression at equal or higher drug doses (e.g., in OV0857-CIS: 96% TGI vs 24% TGI at 5 mg/kg and 95% TGI vs 2% TGI at 2.5 mg/kg of a single IV dose AZD5335 and FRα-MTI, respectively). These data indicate that AZD5335 is a promising therapeutic candidate for the treatment of ovarian cancers across the spectrum of FRα-expression."

Late-breaking abstract • Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1 • GPI

AstraZeneca advances its pipeline and highlights progress in immuno-oncology, ADCs, cell therapy and epigenetics at AACR (AstraZeneca Press Release) - "AstraZeneca will present new data across its diverse, industry-leading Oncology pipeline and portfolio at the American Association for Cancer Research (AACR) Annual Meeting, 14 to 19 April 2023....Two oral presentations will feature the first preclinical and translational results for AZD9592, a bispecific ADC designed to deliver targeted chemotherapy to cancer cells with a topoisomerase inhibitor 1 (TOP1i) warhead using the Company’s proprietary linker technology....In addition, the first preclinical results will be presented for another ADC, AZD5335, a promising therapeutic candidate for the treatment of certain ovarian cancers."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

FONTANA: Phase I/IIa Study for AZD5335 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors (clinicaltrials.gov) - P1/2 | N=150 | Not yet recruiting | Sponsor: AstraZeneca

Combination therapy • Monotherapy • New P1/2 trial • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • MUC16