Study to Test How Well Patients With Advanced Solid Tumors Respond to Treatment With the Elimusertib in Combination With Pembrolizumab, to Find the Optimal Dose for Patients, How the Drug is Tolerated and the Way the Body Absorbs, Distributes and Discharges the Drug

Advanced Solid Tumors Clinical Trial

Official title:

A Multicenter, Non-randomized, Open-label Phase 1b Study to Determine the Maximum Tolerated and Recommended Phase 2 Dose of the ATR Inhibitor Elimusertib in Combination With Pembrolizumab and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity in Participants With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04095273
• Other study ID #: 19741
• Secondary ID: KEYNOTE-919MK-34
• Status: Completed
• Phase: Phase 1
• Start date: September 30, 2019
• Est. completion date: April 11, 2023

Study information

• Verified date: March 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to test how well patients with advanced solid tumors respond to treatment with elimusertib (BAY1895344) in combination with pembrolizumab. In addition researchers want to find for patients the optimal dose of elimusertib in combination with pembrolizumab, how the drug is tolerated and the way the body absorbs, distributes and discharges the drug. The study medication, elimusertib, works by blocking a substance (ATR Kinase) which is produced by the body and is important for the growth of tumor cells. Pembrolizumab is an immunologic checkpoint blocker that promotes an immune response against the tumor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: April 11, 2023
• Est. primary completion date: November 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must be =18 years of age inclusive, at the time of signing the informed consent.

• Presence of the putative biomarkers of DDR deficiency in tumor and/or other tissues (dose escalation only).

• Participants must have histologically confirmed solid tumors .

• Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 1.

• Adequate bone marrow function as assessed by laboratory tests to be conducted within 7 days before the first dose of study intervention.

• Participants must have adequate kidney function, as assessed by the estimated glomerular filtration rate (eGFR) > 40 mL/min per 1.73 m*2 within 7 days before the first dose of study intervention.

• Participants must have adequate liver function as assessed by laboratory tests to be conducted within 7 days before the first dose of study intervention.

• Participants must have adequate coagulation, as assessed by laboratory tests as applicable, (to be conducted within 7 days before the first dose of study intervention) or be on stable anti-coagulation treatment.

• Adequate cardiac function per institutional normal measured by echocardiography (recommended) or multigated acquisition (MUGA) scan/cardiac MRI per institutional guidelines.

• Participants must have measurable disease (at least one measurable lesion) as per RECIST 1.1, or evaluable disease according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) classification as applicable. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions

Exclusion Criteria:

• Ongoing infections of Common terminology criteria for adverse events (CTCAE) grade =2 not responding to therapy or active clinically serious infections.

• Participants with

• Known human immunodeficiency virus (HIV)

• Active Hepatitis B infection (positive for Hepatitis B surface antigen (HBsAg)/ Hepatitis B virus (HBV) DNA).

• Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA results greater than the lower limits of detection of the assay).

• Active autoimmune disease (active defined as having autoimmune disease related symptoms and detectable autoantibodies) that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

• Diagnosis of immunodeficiency or participant is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor.

• Pleural effusion or ascites that causes respiratory compromise (CTCAE Grade = 2 dyspnea).

• History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class >II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers, calcium channel blockers, and digoxin are permitted)

• Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion)

• Moderate or severe hepatic impairment, i.e., Child-Pugh class B or C.

• History of organ allograft transplantation

• Evidence or history of bleeding disorder, i.e., any hemorrhage / bleeding event of CTCAE Grade > 2 within 4 weeks before the first dose of study intervention

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• Elimusertib (BAY1895344)
Study drugs will be administered as scheduled
• Pembrolizumab (Keytruda®)
Study drugs will be administered as scheduled

Locations

Country	Name	City	State
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Germany	Eberhard-Karls-Universität Tübingen	Tübingen	Baden-Württemberg
Spain	Fundacion Jimenez Diaz (Clinica de la Concepcion)	Madrid
Spain	Hospital Madrid Norte Sanchinarro	Madrid
Switzerland	Ospedale Regionale di Bellinzona e Valli	Bellinzona	Ticino
Switzerland	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen
United Kingdom	Freeman Hospital	Newcastle	Tyne And Wear
United Kingdom	Royal Marsden NHS Trust (Surrey)	Sutton	Surrey
United States	Johns Hopkins Hospital/Health System	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Ohio State University	Columbus	Ohio
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	Weill Cornell Medical College	New York	New York
United States	Stanford University	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Germany,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs)		Up to 30 days after last study intervention administration
Primary	Severity of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs)		Up to 30 days after last study intervention administration
Primary	Frequency of Dose limiting toxicities (DLTs) at each dose level during dose escalation of BAY1895344		Cycle 1 (21 days)
Primary	Recommended phase II dose (RP2D) of BAY1895344	The RP2D will be determined in dose expansion part based on multiple parameters (i.e., safety, tolerability, PK, pharmacodynamics, efficacy) and will be a dose equal to or lower than the MTD (Maximum Tolerated Dose).	Up to 24 months
Secondary	Cmax of Elimusertib		Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2)
Secondary	AUC(0-12) of Elimusertib	If the main parameters AUC(0-12) cannot be calculated reliably, it might become necessary to appoint the additional parameters AUC(0-tlast) as secondary variables.	Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2)
Secondary	Cmax,md of Elimusertib		Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2)
Secondary	AUC(0-12)md of Elimusertib	If the main parameters AUC(0-12)md cannot be calculated reliably, it might become necessary to appoint the additional parameters AUC(0-tlast)md as secondary variables.	Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2)
Secondary	Incidence of Complete response (CR)	Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)	Up to 24 months
Secondary	Incidence of partial response (PR)	Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)	Up to 24 months
Secondary	Incidence of stable disease (SD)	Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)	Up to 24 months
Secondary	Incidence of progressive disease (PD)	Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)	Up to 24 months
Secondary	Objective Response Rate (ORR)		Up to 24 months
Secondary	Disease control rate (DCR)		Up to 24 months

External Links

•   Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.
•   Click here to find information about studies related to Bayer Healthcare products conducted in Europe.