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

NCT ID: NCT01723475

Last Updated: 2019-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-02
• Study Completion Date: 2018-09-26

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

Study Design

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

Study Groups

BAY2010112 (s.c.)

Group Type: EXPERIMENTAL

BAY2010112

Intervention Type: 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 (c.i.v.)

Group Type: EXPERIMENTAL

BAY2010112

Intervention Type: BIOLOGICAL

Continuous intravenous infusion (c.i.v.) administration. Starting dose will be 5 µg ; dose will be escalated dependent on any dose limiting toxicities.

Interventions

BAY2010112

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

Intervention Type: BIOLOGICAL

BAY2010112

Continuous intravenous infusion (c.i.v.) administration. Starting dose will be 5 µg ; dose will be escalated dependent on any dose limiting toxicities.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

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

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Linz, Upper Austria, Austria

Vienna, , Austria

Heidelberg, Baden-Wurttemberg, Germany

Würzburg, Bavaria, Germany

Berlin, , Germany

Countries

Austria; Germany

References

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.

Reference Type: RESULT

PMID: 23623807 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37942314 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33172323 (View on PubMed)

Related Links

http://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe

https://clinicaltrials.bayer.com/

Click here to find results for studies related to Bayer products.

Other Identifiers

2012-000691-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

15590

Identifier Type: -

Identifier Source: org_study_id