[FONTANA] Phase I/​IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors

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.

AZD5335 is a folate receptor α (FRα)-targeted antibody-drug conjugate.

This randomized study has 4 modules:

Experimental - Module 1- AZD5335 Monotherapy: Administration of AZD5335 (IV Antibody-drug conjugate) Monotherapy

Experimental: Module 2: AZD5335 + Saruparib: Administration of AZD5335 (IV) + Saruparib (oral)

Experimental: Module 3: AZD5335 + Bevacizumab: Administration of AZD5335 + Bevacizumab (IV)

Experimental - Module 4 - AZD5335 + Carboplatin +/- Bevacizumab: Administration of AZD5335 + Carboplatin +/- Bevacizumab (IV)

Inclusion Criteria:

• For participants who have previously received targeted therapies such as ADCs, a fresh baseline biopsy will be required.
• Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy. Participants with contraindications or who refuse therapy in accordance with local practice may also be considered provided that it is documented that he/she was informed about all therapeutic options.
• A previously irradiated lesion can be considered a target lesion if the lesion is progressing and well defined.

Exclusion Criteria:

• Patients with spinal cord compression or a history of leptomeningeal carcinomatosis.
• Patients with brain metastases unless, asymptomatic, stable, and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to first dose of study intervention.
• Treatment with any of the protocol defined medications, without adequate washout periods or time before the first dose of study intervention.
• Patient has ILD/pneumonitis or has a 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.
• Patients with a history of radiation pneumonitis which has clinically and radiologically resolved and not requiring treatment with steroids may be eligible.