Description:
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.
Title
- Brief Title: A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer
- Official Title: 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.
Clinical Trial IDs
- ORG STUDY ID:
D9320C00001
- NCT ID:
NCT02991911
Conditions
- Metastatic Castration Resistant Prostate Cancer
Interventions
Drug | Synonyms | Arms |
---|
MEDI3726 Post-Chemo | | Arm A |
MEDI3726 Pre-Chemo | | Arm B |
MEDI3726 & Enzalutamide Combo | | Arm C |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A | Experimental | MEDI3726 Post-Chemo | |
Arm B | Experimental | MEDI3726 Pre-Chemo | |
Arm C | Experimental | MEDI3726 & Enzalutamide Combo | - MEDI3726 & Enzalutamide Combo
|
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:
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.
Maximum Eligible Age: | 100 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Occurrence of adverse events (AEs) |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | Safety Endpoint |
Secondary Outcome Measures
Measure: | Response Evaluation Criteria in Solid Tumors (RECIST) response |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | Response according to RECIST version 1.1 |
Measure: | PSA50 response |
Time Frame: | From time of fist dose through at least 12 weeks after first dose of MEDI3726 |
Safety Issue: | |
Description: | Reduction in PSA level of 50% (PSA50) or more compared with baseline |
Measure: | Circulating Tumor Cell (CTC) response |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | Conversion in the CTC count defined as a reduction from ≥ 5 cells/7.5 mL blood to < 5 cells/7.5 mL blood with a confirmatory assessment at least 4 weeks later |
Measure: | Safety and tolerability of MEDI3726 in combination with Enzalutamide |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide |
Safety Issue: | |
Description: | Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline |
Measure: | MEDI3726 plasma concentrations for pharmacokinetics (PK) |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | |
Measure: | MEDI3726 maximum observed concentration for PK |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | |
Measure: | MEDI3726 area under the concentration-time curve for PK |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | |
Measure: | MEDI3726 clearance for PK |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | |
Measure: | MEDI3726 terminal half-life for PK |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | |
Measure: | Number and percentage of subjects who develop anti-drug antibodies (ADAs) |
Time Frame: | From time of informed consent through 90 days after last dose of MEDI3726 |
Safety Issue: | |
Description: | To determine the immunogenicity of MEDI3726 |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | MedImmune LLC |
Trial Keywords
- metastatic, prostate cancer
Last Updated
January 18, 2020