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:

1. Radiographic progression.

2. 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:

1. Required for Arm A.

2. Excluded for Arm B.

3. 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:

1. At least 14 days before the first dose of investigational product since
completion of treatment with abiraterone or enzalutamide

2. At least 14 days before the first dose of investigational product since
completion of prior taxane-based chemotherapy

3. At least 28 days before the first dose of investigational product since
completion of treatment with Radium-223.

4. 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:

1. More than 25% of marrow-bearing bone has been irradiated.

2. 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.