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

• ClinicalTrials.gov Identifier: NCT02991911
• Recruitment Status: Completed
• First Posted: December 14, 2016
• Last Update Posted: January 18, 2020
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Tracking Information

• First Submitted Date: December 1, 2016
• First Posted Date: December 14, 2016
• Last Update Posted Date: January 18, 2020
• Actual Study Start Date: January 6, 2017
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 21, 2018)

• 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 laboratory parameters from baseline [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  Safety Endpoint
• 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 electrocardiogram (ECG) results from baseline [ Time Frame: From time of informed consent through 21 days after last dose of MEDI3726 ]
  Safety Endpoint

Original Primary Outcome Measures (submitted: December 9, 2016)

• Occurrence of adverse events (AEs) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• Occurrence of serious adverse events (SAEs) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• Occurrence of dose-limiting toxicities (DLTs) [ Time Frame: From time of informed consent through 21 days after first dose of MEDI3726 ]
• 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 ]
• 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 ]
• 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 ]

Current Secondary Outcome Measures (submitted: June 21, 2018)

• Response Evaluation Criteria in Solid Tumors (RECIST) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  Response according to RECIST version 1.1
• PSA50 response [ Time Frame: From time of fist dose through at least 12 weeks after first dose of MEDI3726 ]
  Reduction in PSA level of 50% (PSA50) or more compared with baseline
• Circulating Tumor Cell (CTC) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  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
• 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 ]
  Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline
• MEDI3726 plasma concentrations for pharmacokinetics (PK) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 maximum observed concentration for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 area under the concentration-time curve for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 clearance for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 terminal half-life for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• 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 ]
  To determine the immunogenicity of MEDI3726

Original Secondary Outcome Measures (submitted: December 9, 2016)

• Response Evaluation Criteria in Solid Tumors (RECIST) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  Response according to RECIST version 1.1
• PSA50 response [ Time Frame: From time of informed consent through at least 12 weeks after last dose of MEDI3726 ]
  Reduction in PSA level of 50% (PSA50) or more compared with baseline
• Circulating Tumor Cell (CTC) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  Conversion in the CTC count defined as a reduction from ≥ 5 cells/7.5 mL blood to < 5 cells/7.5 mL blood
• 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 ]
  Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline
• MEDI3726 plasma concentrations for pharmacokinetics (PK) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 maximum observed concentration for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 area under the concentration-time curve for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 clearance for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• MEDI3726 terminal half-life for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
• 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 ]
  To determine the immunogenicity of MEDI3726

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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.
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Castration Resistant Prostate Cancer

Intervention

• Biological: MEDI3726 Post-Chemo
  Single agent MEDI3726 after abiraterone or enzalutatmide, with a prior taxane-based chemotherapy in the mCRPC setting
• Biological: MEDI3726 Pre-Chemo
  Single agent MEDI3726 after abiraterone or enzalutatmide, without a prior taxane-based chemotherapy in the mCRPC setting
• Biological: MEDI3726 & Enzalutamide Combo
  MEDI3726 in combination with Enzalutatmide after prior treatment with abiraterone, with or without a prior taxane-based chemotherapy in the mCRPC setting

Study Arms

• Experimental: Arm A
  MEDI3726 Post-Chemo
  Intervention: Biological: MEDI3726 Post-Chemo
• Experimental: Arm B
  MEDI3726 Pre-Chemo
  Intervention: Biological: MEDI3726 Pre-Chemo
• Experimental: Arm C
  MEDI3726 & Enzalutamide Combo
  Intervention: Biological: MEDI3726 & Enzalutamide Combo

• Publications *: Cho S, Zammarchi F, Williams DG, Havenith CEG, Monks NR, Tyrer P, D'Hooge F, Fleming R, Vashisht K, Dimasi N, Bertelli F, Corbett S, Adams L, Reinert HW, Dissanayake S, Britten CE, King W, Dacosta K, Tammali R, Schifferli K, Strout P, Korade M 3rd, Masson Hinrichs MJ, Chivers S, Corey E, Liu H, Kim S, Bander NH, Howard PW, Hartley JA, Coats S, Tice DA, Herbst R, van Berkel PH. Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer. Mol Cancer Ther. 2018 Oct;17(10):2176-2186. doi: 10.1158/1535-7163.MCT-17-0982. Epub 2018 Jul 31.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 3, 2019): 33
• Original Estimated Enrollment (submitted: December 9, 2016): 224
• Actual Study Completion Date: September 30, 2019
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT02991911
• Other Study ID Numbers: D9320C00001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: MedImmune LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: MedImmune LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MedImmune LLC; Sponsor GmbH

• PRS Account: MedImmune LLC
• Verification Date: January 2020