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

NCT04095273 | Completed Phase 1 FDA Drug

• 4 other identifiers: 19741KEYNOTE-919MK-3475-9192018-003420-36
• Study Type: interventional
• Target: 56
• Locations: 5 countries
• Sites: 16

Brief 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.

Conditions

Advanced Solid Tumors

Keywords

DDR (Deoxyribonucleic acid damage repair),; ATR (ataxia-telangiectasia and Rad3 related protein)inhibitor,

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs)

  Up to 30 days after last study intervention administration

• Severity of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs)

  Up to 30 days after last study intervention administration

• Frequency of Dose limiting toxicities (DLTs) at each dose level during dose escalation of BAY1895344

  Cycle 1 (21 days)

• 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 Outcomes (10)

• Cmax of Elimusertib

  Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2)

• AUC(0-12) of Elimusertib

  Cycle 1 (21 days), Day 8 (dosing schedule 1) or Cycle 1 (21 days), Day 1 (dosing schedule 2)

• Cmax,md of Elimusertib

  Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2)

• AUC(0-12)md of Elimusertib

  Cycle 1 (21 days), Day 17 (dosing schedule 1) or Cycle 1 (21 days), Day 10 (dosing schedule 2)

• Incidence of Complete response (CR)

  Up to 24 months

Study Arms (13)

Dose escalation of Elimusertib

EXPERIMENTAL

2 dose levels of Elimusertib are planned

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 1a of Elimusertib

EXPERIMENTAL

Participants with advanced hormone-receptor-positive, Human epidermal growth factor receptor 2 negative breast cancer (HER2-negative BC), known to be positive for Ataxia-telangiectasia mutated (ATM) loss and/or ATM deleterious alterations who have not received prior treatment with immunotherapy. Participants with known microsatellite instability-high (MSI-H) cannot be included

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 1b of Elimusertib

EXPERIMENTAL

Participants with advanced hormone-receptor-positive, HER2-negative BC, known to be DDR deficiency biomarker-positive (except ATM loss/mutation) who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 2a of Elimusertib

EXPERIMENTAL

Participants with advanced Colorectal cancer (CRC) known to be positive for ATM loss and/or ATM deleterious alterations who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 2b of Elimusertib

EXPERIMENTAL

Participants with advanced CRC, known to be DDR deficiency biomarker -positive (except ATM loss/mutation) who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 3 of Elimusertib

EXPERIMENTAL

Participants with advanced Gastric/gastroesophageal junction cancer (GC/GEJ) known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 3a of Elimusertib

EXPERIMENTAL

Participants with advanced GC/GEJ cancer and without DDR deficiency alterations as described above. Variants of unknown significance (VUS) of the DDR gene alterations are eligible. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 4 of Elimusertib

EXPERIMENTAL

Participants with advanced Non-small cell lung cancer (NSCLC) known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 4a of Elimusertib

EXPERIMENTAL

Participants with advanced NSCLC and without DDR deficiency alterations as described above. VUS of the DDR gene alterations are eligible. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 5 of Elimusertib

EXPERIMENTAL

Participants with advanced pancreatic cancer, known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 5a of Elimusertib

EXPERIMENTAL

Participants with advanced pancreatic cancer and without DDR deficiency alterations as described above, who have not received prior treatment with immunotherapy. VUS of the DDR gene alterations are eligible. Participants with known MSI-H cannot be included.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 6 of Elimusertib

EXPERIMENTAL

Participants with advanced Metastatic castration-resistant prostate cancer (mCRPC), known to be DDR deficiency biomarker positive (incl. ATM mutation) and/or positive for ATM loss who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Dose expansion cohort 6a of Elimusertib

EXPERIMENTAL

Participants with advanced mCRPC and without DDR deficiency alterations as described above, who have not received prior treatment with immunotherapy. VUS of the DDR gene alterations are eligible. Participants with known MSI-H cannot be included.

Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

Interventions

Elimusertib (BAY1895344) DRUG

Study drugs will be administered as scheduled

Dose escalation of Elimusertib; Dose expansion cohort 1a of Elimusertib; Dose expansion cohort 1b of Elimusertib; Dose expansion cohort 2a of Elimusertib; Dose expansion cohort 2b of Elimusertib; Dose expansion cohort 3 of Elimusertib; Dose expansion cohort 3a of Elimusertib; Dose expansion cohort 4 of Elimusertib; Dose expansion cohort 4a of Elimusertib; Dose expansion cohort 5 of Elimusertib; Dose expansion cohort 5a of Elimusertib; Dose expansion cohort 6 of Elimusertib; Dose expansion cohort 6a of Elimusertib

Pembrolizumab (Keytruda®) DRUG

Study drugs will be administered as scheduled

Dose escalation of Elimusertib; Dose expansion cohort 1a of Elimusertib; Dose expansion cohort 1b of Elimusertib; Dose expansion cohort 2a of Elimusertib; Dose expansion cohort 2b of Elimusertib; Dose expansion cohort 3 of Elimusertib; Dose expansion cohort 3a of Elimusertib; Dose expansion cohort 4 of Elimusertib; Dose expansion cohort 4a of Elimusertib; Dose expansion cohort 5 of Elimusertib; Dose expansion cohort 5a of Elimusertib; Dose expansion cohort 6 of Elimusertib; Dose expansion cohort 6a of Elimusertib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (16)

Stanford University

Palo Alto, California, 94304, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Johns Hopkins Hospital/Health System

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115-6084, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204-2990, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4000, United States

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Eberhard-Karls-Universität Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Fundacion Jimenez Diaz (Clinica de la Concepcion)

Madrid, 28040, Spain

Location

Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain

Location

Kantonsspital St. Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Ospedale Regionale di Bellinzona e Valli

Bellinzona, Canton Ticino, 6500, Switzerland

Location

Royal Marsden NHS Trust (Surrey)

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Freeman Hospital

Newcastle, Tyne and Wear, NE7 7DN, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies; Ataxia Telangiectasia

Interventions

BAY 1895344; pembrolizumab

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Neurologic Manifestations; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 19, 2019
• Study Start: September 30, 2019
• Primary Completion: November 24, 2022
• Study Completion: April 11, 2023
• Last Updated: April 2, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); DE (2); CH (2); US (8); ES (2)