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Advanced Solid TumorsPhase 1NCT04095273

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 Phase 1 study testing Elimusertib (BAY1895344) and Pembrolizumab (Keytruda®) in people with Advanced Solid Tumors, run by Bayer at 16 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Elimusertib (BAY1895344) and Pembrolizumab (Keytruda®)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
16 sitesin 5 countries
Study dates
30 Sep 2019to 11 Apr 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

16 sites in 5 countries.

16 sites in 5 countries

United States8 sites

  • Johns Hopkins Hospital/Health System

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115-6084

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204-2990

  • Ohio State University

    Columbus, Ohio, 43210

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4000

  • Yale Cancer Center

    New Haven, Connecticut, 06519

  • Weill Cornell Medical College

    New York, New York, 10021

  • Stanford University

    Palo Alto, California, 94304

Other trials in United States

Germany2 sites

  • Universitätsklinikum Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

  • Eberhard-Karls-Universität Tübingen

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Spain2 sites

  • Fundacion Jimenez Diaz (Clinica de la Concepcion)

    Madrid, 28040

  • Hospital Madrid Norte Sanchinarro

    Madrid, 28050

Other trials in Spain

Switzerland2 sites

  • Ospedale Regionale di Bellinzona e Valli

    Bellinzona, Canton Ticino, 6500

  • Kantonsspital St. Gallen

    Sankt Gallen, Canton of St. Gallen, 9007

Other trials in Switzerland

United Kingdom2 sites

  • Freeman Hospital

    Newcastle, Tyne and Wear, NE7 7DN

  • Royal Marsden NHS Trust (Surrey)

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

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

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.

Being tested
Elimusertib (BAY1895344), Pembrolizumab (Keytruda®)
Keywords
DDR (Deoxyribonucleic acid damage repair),, ATR (ataxia-telangiectasia and Rad3 related protein)inhibitor,
Medical subject headings
Hereditary Sensory and Autonomic Neuropathies, Ataxia Telangiectasia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Elimusertib (BAY1895344)Drug

    Study drugs will be administered as scheduled

  • Pembrolizumab (Keytruda®)Drug

    Study drugs will be administered as scheduled

Study groups in NCT04095273
Study groupRoleWhat they receive
Dose escalation of ElimusertibExperimental2 dose levels of Elimusertib are planned
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 1a of ElimusertibExperimentalParticipants 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
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 1b of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 2a of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 2b of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 3 of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 3a of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 4 of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 4a of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 5 of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 5a of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 6 of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)
Dose expansion cohort 6a of ElimusertibExperimentalParticipants 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.
Receives: Drug: Elimusertib (BAY1895344); Drug: Pembrolizumab (Keytruda®)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 30 days after last study intervention administration

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

    Measured: Up to 30 days after last study intervention administration

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

    Measured: Cycle 1 (21 days)

  4. 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).

    Measured: Up to 24 months

Secondary outcomes (10)

  1. Cmax of Elimusertib

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

  2. 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.

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

  3. Cmax,md of Elimusertib

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

  4. 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.

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

  5. Incidence of Complete response (CR)

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

    Measured: Up to 24 months

  6. Incidence of partial response (PR)

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

    Measured: Up to 24 months

  7. Incidence of stable disease (SD)

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

    Measured: Up to 24 months

  8. Incidence of progressive disease (PD)

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

    Measured: Up to 24 months

  9. Objective Response Rate (ORR)

    Measured: Up to 24 months

  10. Disease control rate (DCR)

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2019
  2. Study start30 Sep 2019
  3. Primary completion24 Nov 2022
  4. Study completion11 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04095273
Sponsor's protocol ID
19741
Other IDs
KEYNOTE-919, MK-3475-919, 2018-003420-36, 2018
Status last verified
Mar 2024
First submitted
18 Sep 2019
Last updated
2 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Elimusertib (BAY1895344) and Pembrolizumab (Keytruda®) in people with Advanced Solid Tumors, run by Bayer at 16 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Germany, Spain, Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment Emergent Adverse Events (TEAEs) including Treatment Emergent Serious Adverse Events (TESAEs) (time frame: Up to 30 days after last study intervention administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04095273.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024; AzTrials last refreshed its copy on 27 Oct 2026.

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