Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Dose escalation will initiate with Part A.1 in which niraparib is used at a lower fixed dose.

If the starting dose level in Part A.1 is tolerated, dose escalation in Part A.2 may be initiated on an optional basis. In Part A.2, niraparib is used at a higher fixed dose.

MTDs and/or candidate RP2Ds for elimusertib used in combination with niraparib at a lower fixed dose.

MTD: Maximum tolerated dose. RP2D: Recommended phase 2 dose.

MTDs and/or candidate RP2Ds for elimusertib used in combination with niraparib at a lower fixed dose.

MTDs and/or candidate RP2Ds for elimusertib used in combination with niraparib at a higher fixed dose.

Elimusertib will be administered in 28-day cycles.

Elimusertib (BAY1895344)

Niraparib will be administered in 28-day cycles.

Bayer Study Director

The purpose of the study is to test how well patients with advanced solid tumors and ovarian cancer respond to treatment with elimusertib in combination with niraparib. In addition researchers want to find for patients the optimal dose of elimusertib in combination with niraparib, 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 produced by the body (ATR Kinase) which is important for the growth of tumor cells. Niraparib works by blocking a substance produced by the body (PARP enzymes) in a way that tumor cells can be killed, or made more susceptible to chemotherapy.

ATR Inhibitor Elimusertib (BAY1895344) Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer

An Open-label Phase 1b Study to Determine the Maximum Tolerated and/or Recommended Phase 2 Dose of the ATR Inhibitor Elimusertib (BAY 1895344) in Combination With PARP Inhibitor Niraparib, in Participants With Recurrent Advanced Solid Tumors and Ovarian Cancer

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

GlaxoSmithKline

Bayer

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, Mantle-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Pharmaceutical Solutions

Patients with histologically confirmed solid tumors or non-Hodgkin's lymphoma (NHL) receive BAY1895344 in a 21-day cycle.

Patients with histologically confirmed solid tumors or NHL known to be positive for ATM loss and/or ATM deleterious mutations receive BAY1895344 in a 28-day cycle.

Japanese patients with histologically confirmed solid tumors receive BAY1895344 at two dose levels: MTD-1 and MTD.

Patients with a) DDR deficiency biomarker-positive advanced solid tumors: castration-resistant prostate cancer (CRPC), HER2-negative breast cancer (BC), colorectal cancer (CRC), and gynecological tumors; OR b) histologically confirmed advanced cancer and loss of ATM regardless of the cancer type receive BAY1895344 at MTD determined at the end of dose escalation.

Patients with histologically confirmed relapsed or refractory MCL receive BAY1895344 at a dose determined after evaluation of multiple BAY1895344 doses in Part A.1

Solution or tablet, oral, to be administered until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator.

The ATR (ataxia-telangiectasia and Rad3 related protein) inhibitor BAY1895344 is developed for the treatment of patients with advanced solid tumors and lymphomas. The purpose of the proposed trial is to evaluate the safety and tolerability of BAY1895344, and to identify the maximum tolerated dose of BAY1895344 that could be safely given to cancer patients. Further, the response of the cancer to the treatment will be determined.

First-in-human Study of ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas

An Open-label, First-in-human, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Maximum Tolerated Dose and / or Recommended Phase II Dose of the ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas

MTD and/or R2PD will be determined in Cycle 1 of Part A, Part A.1 and J-arm of Part A.

The MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 30%, or the maximum dose tested, whichever is achieved first during dose-escalation.

AUC(0-12) and AUC(0-12)md will be evaluated in Part A, A.1 and J-arm of Part A.

Cmax and Cmax,md will be evaluated in Part A, A.1 and J-arm of Part A.

Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease). CRPC: castration resistant prostate cancer; RECIST: Response Evaluation Criteria in Solid Tumors

Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease).

Responses include: CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease).

PCWG3: Prostate Cancer Working Group 3

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Ataxia

Cerebellar Ataxia

Telangiectasis

Ataxia Telangiectasia

Hormones

Pembrolizumab

Immunomodulating Agents

Mitogens

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Study drugs will be administered as scheduled

Pembrolizumab (Keytruda®)

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.

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

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

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).

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.

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.

Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ATR Inhibitor Elimusertib (BAY1895344) Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer	NCT04267939	Advanced Solid ... Ovarian Cancer	Elimusertib (BA... Niraparib	18 Years -	Bayer
First-in-human Study of ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas	NCT03188965	Advanced Solid ... Non-Hodgkin's L... Mantle Cell Lym...	Elimusertib (BA...	18 Years -	Bayer
ATR Inhibitor Elimusertib (BAY1895344) Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer	NCT04267939	Advanced Solid ... Ovarian Cancer	Elimusertib (BA... Niraparib	18 Years -	Bayer
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	Advanced Solid ...	Elimusertib (BA... Pembrolizumab (...	18 Years -	Bayer
ATR Inhibitor Elimusertib (BAY1895344) Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer	NCT04267939	Advanced Solid ... Ovarian Cancer	Elimusertib (BA... Niraparib	18 Years -	Bayer

Spots Global Cancer Trial Database for elimusertib (bay1895344)