A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Metastatic Castration Resistant Prostate Cancer
- Sponsor
- MedImmune LLC
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Number of patients with changes in vital signs from baseline
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI3726 in subjects with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.
Investigators
Eligibility Criteria
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.
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-
- •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.
Outcomes
Primary Outcomes
Number of patients with changes in vital signs from baseline
Time Frame: From time of informed consent through 21 days after last dose of MEDI3726
Safety Endpoint
Number of patients with changes in laboratory parameters from baseline
Time Frame: From time of informed consent through 90 days after last dose of MEDI3726
Safety Endpoint
Occurrence of adverse events (AEs)
Time Frame: From time of informed consent through 90 days after last dose of MEDI3726
Safety Endpoint
Occurrence of serious adverse events (SAEs)
Time Frame: From time of informed consent through 90 days after last dose of MEDI3726
Safety Endpoint
Occurrence of dose-limiting toxicities (DLTs)
Time Frame: From time of first dose through 21 days after first dose of MEDI3726
Safety Endpoint
Number of patients with changes in electrocardiogram (ECG) results from baseline
Time Frame: From time of informed consent through 21 days after last dose of MEDI3726
Safety Endpoint
Secondary Outcomes
- PSA50 response(From time of fist dose through at least 12 weeks after first dose of MEDI3726)
- MEDI3726 plasma concentrations for pharmacokinetics (PK)(From time of informed consent through 90 days after last dose of MEDI3726)
- MEDI3726 terminal half-life for PK(From time of informed consent through 90 days after last dose of MEDI3726)
- Response Evaluation Criteria in Solid Tumors (RECIST) response(From time of informed consent through 90 days after last dose of MEDI3726)
- Circulating Tumor Cell (CTC) response(From time of informed consent through 90 days after last dose of MEDI3726)
- Number and percentage of subjects who develop anti-drug antibodies (ADAs)(From time of informed consent through 90 days after last dose of MEDI3726)
- MEDI3726 area under the concentration-time curve for PK(From time of informed consent through 90 days after last dose of MEDI3726)
- MEDI3726 maximum observed concentration for PK(From time of informed consent through 90 days after last dose of MEDI3726)
- Safety and tolerability of MEDI3726 in combination with Enzalutamide(From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide)
- MEDI3726 clearance for PK(From time of informed consent through 90 days after last dose of MEDI3726)