Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer

Phase 1

Completed

• Conditions: Metastatic Castration Resistant Prostate Cancer (mCRPC)
• Interventions: Drug: BAY2315497 Injection; Drug: Darolutamide(BAY1841788)

• Registration Number: NCT03724747
• Lead Sponsor: Bayer

Brief Summary

The study medication (BAY 2315497 Injection) is a thorium-227 labeled immuno-conjugate, specific for the prostate-specific membrane antigen (PSMA), which will be evaluated in patients with metastatic castration resistant prostate cancer. In this study, this investigational medication will be administered to patients for the first time. The primary objective of the study is to define the safety and tolerability profile and Maximal Tolerated Dose (MTD) of BAY2315497 Injection alone, or in combination with darolutamide. The secondary objectives are to determine the recommended dose for further clinical development of BAY2315497 Injection alone, or in combination with darolutamide and to investigate how the study drug is distributed and cleared from the body.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2018-10-23
• Study First Submitted QC: 2018-10-29
• Study First Posted: 2018-10-30
• Study Start: 2018-12-18
• Primary Completion: 2022-08-25
• Study Completion: 2024-10-31
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 63

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BAY2315497 dose escalation in combination with darolutamide	BAY2315497 Injection	The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme. In addition, Darolutamide oral dosing at the approved dose of twice daily 600 mg will be initiated 14 days prior to the first BAY2315497 Injection dose on Day 1 of the first cycle. Daily darolutamide dosing will continue throughout the entire BAY2315497 Injection treatment period until withdrawal criteria from study treatment period are met.
BAY2315497 dose escalation in combination with darolutamide	Darolutamide(BAY1841788)	The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme. In addition, Darolutamide oral dosing at the approved dose of twice daily 600 mg will be initiated 14 days prior to the first BAY2315497 Injection dose on Day 1 of the first cycle. Daily darolutamide dosing will continue throughout the entire BAY2315497 Injection treatment period until withdrawal criteria from study treatment period are met.
BAY2315497 dose expansion:Dose regimen 1	BAY2315497 Injection	The thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY2315497 Injection, observed in the course of the dose escalation.
BAY2315497 dose escalation	BAY2315497 Injection	The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme. The total antibody dose of 50 mg will be evaluated first; on the basis of emerging clinical data, doses within the range of 20-100 mg may be investigated.
BAY2315497 dose expansion:Dose regimen 2	BAY2315497 Injection	The thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY2315497 Injection, observed in the course of the dose escalation.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) of BAY2315497 injection in combination with darolutamide	Cycle 1 (42 days)	The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.
Maximum tolerated dose (MTD) of BAY2315497 injection	Cycle 1 (42 days)	The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.

Secondary Outcome Measures

Name	Time	Method
Cmax of radium of BAY2315497 Injection	Cycle 1 (From day 1 to 43)
Cmax of total antibody of BAY2315497 Injection	Cycle 1 (From day 1 to 43)
AUC(0-42) days of total antibody of BAY2315497 Injection	Cycle 1 (From day 1 to 43)
Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium of BAY2315497 Injection	Cycle 1 (From day 1 to 43)
Recommended dose for further clinical development of BAY2315497 injection in combination with darolutamide	Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented)	The dose / regimen recommended for further clinical development will be defined after evaluation of the safety, PK and overall clinical data, collected in cycle 1 and subsequent cycles, in the dose escalation and dose expansion parts of the study.
Cmax of radium of BAY2315497 Injection in combination with darolutamide	Cycle 1 (From day 1 to 43)
Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection	Cycle 1 (From day 1 to 43)
AUC(0-42) days of radium of BAY2315497 Injection	Cycle 1 (From day 1 to 43)
Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium of BAY2315497 Injection in combination with darolutamide	Cycle 1 (From day 1 to 43)
AUC(0-42) days of radium of BAY2315497 Injection in combination with darolutamide	Cycle 1 (From day 1 to 43)
Cmax of total antibody of BAY2315497 Injection in combination with darolutamide	Cycle 1 (From day 1 to 43)
AUC(0-42) days of total antibody of BAY2315497 Injection in combination with darolutamide	Cycle 1 (From day 1 to 43)
Recommended dose for further clinical development of BAY2315497 injection	Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented)	The dose / regimen recommended for further clinical development will be defined after evaluation of the safety, PK and overall clinical data, collected in cycle 1 and subsequent cycles, in the dose escalation and dose expansion parts of the study.
Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection in combination with darolutamide	Cycle 1 (From day 1 to 43)

Trial Locations

Locations (5)

Tulane Medical Center; 🇺🇸 New Orleans, Louisiana, United States

Royal Marsden NHS Trust (Surrey); 🇬🇧 Sutton, Surrey, United Kingdom

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

GU Research Network, LLC; 🇺🇸 Omaha, Nebraska, United States

HUS, Meilahden sairaala; 🇫🇮 Helsinki, Finland