Clinical trial NCT02991911: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Castration Resistant Prostate Cancer
Keywords: metastatic, prostate cancer
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2016-12-14
Enrollment: 33
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Occurrence of adverse events (AEs)
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: Occurrence of serious adverse events (SAEs)
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: Occurrence of dose-limiting toxicities (DLTs)
timeFrame: From time of first dose through 21 days after first dose of MEDI3726
measure: Number of patients with changes in laboratory parameters from baseline
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: Number of patients with changes in vital signs from baseline
timeFrame: From time of informed consent through 21 days after last dose of MEDI3726
measure: Number of patients with changes in electrocardiogram (ECG) results from baseline
timeFrame: From time of informed consent through 21 days after last dose of MEDI3726
Secondary outcomes:
measure: Response Evaluation Criteria in Solid Tumors (RECIST) response
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: PSA50 response
timeFrame: From time of fist dose through at least 12 weeks after first dose of MEDI3726
measure: Circulating Tumor Cell (CTC) response
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: Safety and tolerability of MEDI3726 in combination with Enzalutamide
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide
measure: MEDI3726 plasma concentrations for pharmacokinetics (PK)
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 maximum observed concentration for PK
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 area under the concentration-time curve for PK
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 clearance for PK
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 terminal half-life for PK
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
measure: Number and percentage of subjects who develop anti-drug antibodies (ADAs)
timeFrame: From time of informed consent through 90 days after last dose of MEDI3726
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Chur
country: Switzerland
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Sponsor GmbH
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: 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.