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

NCT ID: NCT02991911

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-06
• Study Completion Date: 2019-09-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

MEDI3726 Post-Chemo

Group Type: EXPERIMENTAL

MEDI3726 Post-Chemo

Intervention Type: BIOLOGICAL

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

Arm B

MEDI3726 Pre-Chemo

Group Type: EXPERIMENTAL

MEDI3726 Pre-Chemo

Intervention Type: BIOLOGICAL

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

Arm C

MEDI3726 \& Enzalutamide Combo

Group Type: EXPERIMENTAL

MEDI3726 & Enzalutamide Combo

Intervention Type: BIOLOGICAL

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

Interventions

MEDI3726 Post-Chemo

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

Intervention Type: BIOLOGICAL

MEDI3726 Pre-Chemo

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

Intervention Type: 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

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MedImmune LLC

Role: STUDY_DIRECTOR

Sponsor GmbH

Locations

Research Site

New Haven, Connecticut, United States

Research Site

Sarasota, Florida, United States

Research Site

Norfolk, Virginia, United States

Research Site

Chur, , Switzerland

Research Site

London, , United Kingdom

Countries

United States; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30065100 (View on PubMed)

Other Identifiers

D9320C00001

Identifier Type: -

Identifier Source: org_study_id