A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer

Inclusion criteria

• Age ≥ 18 years at the time of screening.
• Histologically confirmed diagnosis of metastatic castration-resistant prostate adenocarcinoma (mCRPC).
• Documented PD in subjects with mCRPC as assessed by the Investigator and defined by at least one of the following according to the PCWG3 criteria:

• Radiographic progression.
• PSA progression.
• Prior exposure to abiraterone or enzalutamide of at least 12 weeks in the mCRPC setting.

NOTE: Subjects who have received both abiraterone and enzalutamide in the mCRPC setting are eligible.

• In dose escalation: Prior taxane-based chemotherapy in the mCRPC setting is:

• Required for Arm A.
• Excluded for Arm B.
• Optional for Arm C.

Exclusion criteria

• Subjects with neuroendocrine, neuroendocrine differentiation and/or small cell prostate cancer.
• The subject has received any conventional or investigational anti-cancer treatment within 21 days before the first dose of investigational product, with the following modifications:

• At least 14 days before the first dose of investigational product since completion of treatment with abiraterone or enzalutamide
• At least 14 days before the first dose of investigational product since completion of prior taxane-based chemotherapy
• At least 28 days before the first dose of investigational product since completion of treatment with Radium-223.
• At least 42 days before the first dose of investigational product since completion of prior bicalutamide and nilutamide treatment.

NOTE: An LHRH agonist or antagonist required for ongoing testosterone suppression will be permitted if Inclusion Criterion is satisfied.

• Prior exposure to PSMA-directed therapies.
• Subjects with previous radiotherapy for the treatment of unresectable, locally advanced or metastatic prostate cancer are excluded if:

• More than 25% of marrow-bearing bone has been irradiated.
• The last fraction of radiotherapy has been administered within approximately 2 weeks prior to the first dose of investigational product.
• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to the first dose of investigational product.
• Subjects with known history of peripheral vasculopathies including, but not limited to, macro and microangiopathies secondary to diabetes, peripheral arteriopathy of any cause, intermittent claudication, repeated and/or non-healing ulcers of any cause.