First-in-man Dose Escalation Study of BAY2010112 in Patients With Prostate Cancer

NCT01723475 | Completed Phase 1 DMC

• 2 other identifiers: 155902012-000691-42
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 5

Brief Summary

This is the first study where BAY2010112 is given to humans. Patients with castration resistant prostate cancer will be treated. Every patient will receive drug treatment, there is no placebo group. Patients will receive different dosages of BAY2010112 to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY2010112. The study will also assess the pharmacokinetics and the clinical efficacy of BAY2010112. BAY2010112 will be given daily as subcutaneous injection or as continuous intravenous infusion. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.

Conditions

Prostatic Neoplasms

Keywords

Phase I; Dose Escalation; Prostate cancer; Antibodies; Bispecific T-cell Engager (BiTE)

Outcome Measures

Primary Outcomes (2)

• Number of participants with Adverse Events as a Measure of Safety and Tolerability

  Up to 2 years or longer if indicated

• Maximum Tolerated Dose (MTD)

  MTD is measured by adverse event profile at the end of Cycle 1. MTD will be the highest dose level achieved during dose escalation where the incidence of dose-limiting toxicities (DLTs) is below 20%

  Up to 2 years or longer if indicated

Secondary Outcomes (4)

• Maximum drug concentration (Cmax) of BAY2010112 in serum after single and multiple doses administration

  Cycle 1 Day1 and 15; (1 Cycle is 21 days long)

• Area under the concentration versus time curve (AUC) from zero to infinity after single (first) and multiple doses of BAY2010112

  Cycle 1 (1 Cycle is 21 days long)

• Tumor response

  Up to 2 years or longer if indicated

• Prostate-specific antigen (PSA) response

  Up to 2 years or longer if indicated

Study Arms (2)

BAY2010112 (s.c.)

EXPERIMENTAL

Biological: BAY2010112

BAY2010112 (c.i.v.)

EXPERIMENTAL

Biological: BAY2010112

Interventions

BAY2010112 BIOLOGICAL

Subcutaneous (s.c.) administration once daily. Starting dose will be 0.5 µg ; dose will be escalated dependent on any dose limiting toxicities

BAY2010112 (s.c.)

Eligibility Criteria

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

You may qualify if:

• Male subjects, aged \>/= 18 years
• Subjects with histologically or cytologically proven advanced castration-resistant prostate cancer (CRPC)
• who failed at least 1 taxane regimen and are refractory to abiraterone and/or enzalutamide therapy OR
• who have actively refused any treatment which would be regarded standard.
• Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist.
• Subjects must have shown progressive disease after discontinuation of anti-androgen therapy (i.e. flutamide, bicalutamide or nilutamide) before study drug treatment.
• Total serum testosterone should be less than 50 ng/ml or 1.7 nmol/L
• Evidence of progressive disease, defined as one or more (Prostate Cancer Working Group 2 (PCWG2) criteria):
• PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
• Nodal (in lymph nodes \>/= 2cm) or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
• Appearance of one more new lesions in bone scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
• Life expectancy of at least 3 months

You may not qualify if:

• Any anticancer therapy or immunotherapy within 4 weeks of start of first dose
• Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
• Prior radiotherapy (local palliative radiotherapy is permitted)
• History of allergic reactions to monoclonal antibody therapy
• History of clinical significant cardiac disease: including unstable angina, acute myocardial infarction within 6 months prior to first study treatment, congestive heart failure ≥New York Heart Association (NYHA) Class III), and arrhythmia requiring therapy except for beta-blockers, calcium channel blockers and digoxin or uncontrolled hypertension, despite optimal medical management
• Clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QT interval corrected for heart rate (QTc)-interval over 450 msec
• Current evidence or history of uncured (i.a. any absolute risk of latent infection) of hepatitis B or C or human immunodeficiency virus (HIV) infection
• Chronic systemic corticosteroid therapy or any other immunosuppressive therapies should have been stopped at screening start
• Seizure disorder requiring therapy (such as steroids or anti-epileptics)
• Subjects unable to inject the study drug subcutaneously for intended s.c. application
• Non-suitable for a central venous access for intended c.i.v. administration

Sponsors & Collaborators

• Bayer: lead

Study Sites (5)

Unknown Facility

Linz, Upper Austria, 4010, Austria

Location

Unknown Facility

Vienna, 1100, Austria

Location

Unknown Facility

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Unknown Facility

Würzburg, Bavaria, 97080, Germany

Location

Unknown Facility

Berlin, 12200, Germany

Location

Related Publications (3)

• Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013 Jun;17(3):385-92. doi: 10.1016/j.cbpa.2013.03.029. Epub 2013 Apr 25.

  PMID: 23623807 RESULT

• Penny HL, Hainline K, Theoharis N, Wu B, Brandl C, Webhofer C, McComb M, Wittemer-Rump S, Koca G, Stienen S, Bargou RC, Hummel HD, Loidl W, Grullich C, Eggert T, Tran B, Mytych DT. Characterization and root cause analysis of immunogenicity to pasotuxizumab (AMG 212), a prostate-specific membrane antigen-targeting bispecific T-cell engager therapy. Front Immunol. 2023 Oct 23;14:1261070. doi: 10.3389/fimmu.2023.1261070. eCollection 2023.

  PMID: 37942314 DERIVED

• Hummel HD, Kufer P, Grullich C, Seggewiss-Bernhardt R, Deschler-Baier B, Chatterjee M, Goebeler ME, Miller K, de Santis M, Loidl W, Dittrich C, Buck A, Lapa C, Thurner A, Wittemer-Rump S, Koca G, Boix O, Docke WD, Finnern R, Kusi H, Ajavon-Hartmann A, Stienen S, Sayehli CM, Polat B, Bargou RC. Pasotuxizumab, a BiTE(R) immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings. Immunotherapy. 2021 Feb;13(2):125-141. doi: 10.2217/imt-2020-0256. Epub 2020 Nov 10.

  PMID: 33172323 DERIVED

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer products.

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 8, 2012
• Study Start: November 2, 2012
• Primary Completion: July 18, 2018
• Study Completion: September 26, 2018
• Last Updated: September 27, 2019

Record last verified: 2019-09

Locations

AU (2); DE (3)