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

NCT02991911 | Completed Phase 1 FDA Drug

• 1 other identifier: D9320C00001
• Study Type: interventional
• Target: 33
• Locations: 3 countries
• Sites: 5

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.

Conditions

Metastatic Castration Resistant Prostate Cancer

Keywords

metastatic, prostate cancer

Outcome Measures

Primary Outcomes (6)

• Occurrence of adverse events (AEs)

  Safety Endpoint

  From time of informed consent through 90 days after last dose of MEDI3726

• Occurrence of serious adverse events (SAEs)

  Safety Endpoint

  From time of informed consent through 90 days after last dose of MEDI3726

• Occurrence of dose-limiting toxicities (DLTs)

  Safety Endpoint

  From time of first dose through 21 days after first dose of MEDI3726

• Number of patients with changes in laboratory parameters from baseline

  Safety Endpoint

  From time of informed consent through 90 days after last dose of MEDI3726

• Number of patients with changes in vital signs from baseline

  Safety Endpoint

  From time of informed consent through 21 days after last dose of MEDI3726

• Number of patients with changes in electrocardiogram (ECG) results from baseline

  Safety Endpoint

  From time of informed consent through 21 days after last dose of MEDI3726

Secondary Outcomes (10)

• Response Evaluation Criteria in Solid Tumors (RECIST) response

  From time of informed consent through 90 days after last dose of MEDI3726

• PSA50 response

  From time of fist dose through at least 12 weeks after first dose of MEDI3726

• Circulating Tumor Cell (CTC) response

  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 plasma concentrations for pharmacokinetics (PK)

  From time of informed consent through 90 days after last dose of MEDI3726

Study Arms (3)

Arm A

EXPERIMENTAL

MEDI3726 Post-Chemo

Biological: MEDI3726 Post-Chemo

Arm B

EXPERIMENTAL

MEDI3726 Pre-Chemo

Biological: MEDI3726 Pre-Chemo

Arm C

EXPERIMENTAL

MEDI3726 \& Enzalutamide Combo

Biological: MEDI3726 & Enzalutamide Combo

Interventions

MEDI3726 Post-Chemo BIOLOGICAL

Single agent MEDI3726 after abiraterone or enzalutatmide, with a prior taxane-based chemotherapy in the mCRPC setting

Arm A

MEDI3726 Pre-Chemo BIOLOGICAL

Single agent MEDI3726 after abiraterone or enzalutatmide, without a prior taxane-based chemotherapy in the mCRPC setting

Arm B

MEDI3726 & Enzalutamide Combo BIOLOGICAL

MEDI3726 in combination with Enzalutatmide after prior treatment with abiraterone, with or without a prior taxane-based chemotherapy in the mCRPC setting

Arm C

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Optional for Arm C.

You may not qualify if:

• 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-223.
• At least 42 days before the first dose of investigational product since completion of prior bicalutamide and nilutamide treatment.
• 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.
• 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.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (5)

Research Site

New Haven, Connecticut, 06519, United States

Location

Research Site

Sarasota, Florida, 34232, United States

Location

Research Site

Norfolk, Virginia, 23502, United States

Location

Research Site

Chur, 7000, Switzerland

Location

Research Site

London, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30065100 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Prostatic Neoplasms

Interventions

MEDI3726

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• MedImmune LLC

  Sponsor GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 14, 2016
• Study Start: January 6, 2017
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

GB (1); US (3); CH (1)