Clinical Trials /

A First-in-Humans Dose Finding Study for an Aryl Hydrocarbon Receptor Inhibitor (AhRi) in Patients With Advanced Cancer

NCT04069026

Description:

In this study researchers want to gather relevant information regarding the safety of BAY2416964 and how well the drug works in participants with a type of solid tumors that cannot be cured by currently available drugs. Researchers want to find the highest dose of BAY2416964 that participants could take without having too many side effects, how the drug is tolerated and the way the body absorbs, distributes and gets rid of the study dug. BAY2416964 is a small molecule which blocks the Aryl Hydrocarbon Receptor (a protein involved in immune cell reaction to tumor cells) allowing the body to use its immune response against the tumor cells.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Find the Highest Dose of BAY2416964 That Participants Could Take Without Having Too Many Side Effects, How the Drug it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Dug and How Well the Drug Works in Patients With Advanced Solid Tumors.
  • Official Title: An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics and Tumor Response Profile of the Aryl Hydrocarbon Receptor Inhibitor (AhRi) BAY 2416964 in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 20201
  • SECONDARY ID: 2019-000722-22
  • NCT ID: NCT04069026

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
BAY2416964Dose escalation of BAY2416964
BAY2416964Dose expansion of BAY2416964 in tumor type specific

Purpose

In this study researchers want to gather relevant information regarding the safety of BAY2416964 and how well the drug works in participants with a type of solid tumors that cannot be cured by currently available drugs. Researchers want to find the highest dose of BAY2416964 that participants could take without having too many side effects, how the drug is tolerated and the way the body absorbs, distributes and gets rid of the study dug. BAY2416964 is a small molecule which blocks the Aryl Hydrocarbon Receptor (a protein involved in immune cell reaction to tumor cells) allowing the body to use its immune response against the tumor cells.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of BAY2416964ExperimentalApproximately 6 dose levels of BAY2416964 are planned
  • BAY2416964
Dose expansion of BAY2416964 in tumor type specificExperimentalPatients with NSCLC, HNSCC and Colorectal cancer MSS
  • BAY2416964

Eligibility Criteria

        Inclusion Criteria:

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

          -  Participants with following histologically or cytologically confirmed advanced solid
             tumors that have progressed after treatment with all available therapies for
             metastatic disease that are known to confer clinical benefit, or are intolerant to
             treatment, or refuse standard treatment. Note: there is no limit to the number of
             prior treatment regimens. Immune checkpoint inhibitors are also allowed in
             pretreatment.

               -  Dose Escalation: all solid tumor types

               -  Tumor type-specific high-dose (MTD or MAD) Expansion cohorts: Will be grouped by
                  tumor type, but no specific biomarker selection will be applied:

                    -  NSCLC

                    -  HNSCC

                    -  Colorectal cancer MSS

               -  Tumor type-specific low-dose Expansion cohort: Any tumor type based on data from
                  dose escalation and expansion indicating pharmacodynamics effect and/or clinical
                  response from the tumor type-specific high-dose(MTD or MAD) expansion.

          -  Have measurable disease per RECIST 1.1 as assessed by CT/MRI. At least one measurable
             lesion by RECIST 1.1 is required. Lesions situated in a previously irradiated area, or
             in an area subjected to other loco-regional therapy, are considered measurable if
             progression has been demonstrated in such lesions.

               -  Life expectancy at least 12 weeks.

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

          -  Adequate bone marrow and organ function as assessed by the following laboratory tests
             performed within 7 days before treatment initiation.

               -  Bone marrow reserve:

                    -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

                    -  Hemoglobin (Hb) ≥ 9.0g/dL, without erythropoietin dependency and without
                       packed red blood cell (pRBC) transfusion within last 2 weeks.

                    -  Platelet count ≥ 100 x 109/L. Transfusion to meet the inclusion criteria
                       will not be allowed.

               -  Hepatic:

                    -  Total bilirubin ≤ 1.5 x the upper limit of normal range (ULN). Known Gilbert
                       syndrome is allowed if total bilirubin is ≤ 3 x ULN.

                    -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x
                       ULN (≤ 5 x ULN for participants with liver metastases).

                    -  Albumin > 25 g/L.

               -  Renal:

                  --- eGFR ≥ 60 mL/min as calculated using the MDRD equation or creatinine level ≤
                  1.5x ULN.

               -  Lipase and amylase ≤ 1.5 x ULN.

               -  Coagulation:

                    -  International normalized ratio (INR) OR prothrombin time (PT) AND activated
                       partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is
                       receiving anticoagulant therapy as long as PT or aPTT is within therapeutic
                       range of intended use of anticoagulants.

          -  Adequate cardiac function, measured by echocardiography within 28 days before start of
             study intervention (left ventricular ejection fraction within institutional normal
             range for age and gender).

        Exclusion Criteria:

          -  Severe (CTCAE v.5 Grade ≥ 3) infections within 4 weeks before the first BAY2416964
             administration, including but not limited to hospitalization for complications of
             infection, bacteremia, or severe pneumonia. Clinically active infections (CTCAE v.5 >
             Grade 1) within 2 weeks before the first BAY2416964 administration.

          -  Active autoimmune disease that has required systemic treatment in 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) is not considered a form
             of systemic treatment and is allowed.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of
             immunosuppressive therapy within 7 days prior the first dose of study intervention.

          -  Congestive heart failure New York Heart Association (NYHA) greater than Class I or
             cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
             calcium channel blockers.

          -  Currently present advanced or metastatic primary brain tumors or untreated brain
             metastases and/or carcinomatous meningitis.

        Participants with previously treated brain metastases may participate if all of the
        following criteria are met:

          -  Must be clinically stable and without requirement of steroid therapy for at least 14
             days prior to first dose of study intervention.

          -  Participants with neurological symptoms must undergo CT/MRI scan of the brain to
             exclude new or progressive brain metastases.

               -  Interstitial lung disease or chronic obstructive pulmonary disease (COPD) with
                  ongoing signs and symptoms at the time of screening. Has a history of
                  (non-infectious) pneumonitis that required steroids or has current pneumonitis.

               -  Significant acute gastrointestinal disorders with diarrhea as a major symptom,
                  e.g. Crohn's disease, malabsorption, or ≥ NCI-CTCAE v. 5.0 Grade 2 diarrhea of
                  any etiology.

               -  History of organ allograft transplantation, including allogeneic bone marrow
                  transplantation.

               -  Prior radiotherapy within 2 weeks before start of BAY2416964. Participants must
                  have recovered from all radiation-related toxicities, not require
                  corticosteroids, and not have had radiation pneumonitis. A 1-week washout is
                  permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

               -  Treatment with systemic immunosuppressant medications (including but not limited
                  to doses > 10 mg/day prednisone or equivalent, cyclophosphamide, azathioprine,
                  methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents)
                  within 2 weeks before the first BAY2416964 administration.

        The use of inhaled corticosteroids, or low doses of glucocorticoids (no more than 10 mg/day
        prednisone or equivalent; if a higher dose would be needed to maintain adrenal function
        investigator must obtain approval from sponsor), and mineralocorticoids (e.g.
        fludrocortisone for adrenal insufficiency) is allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The incidence of treatment emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs) and and dose-limiting toxicities (DLTs)
Time Frame:Up to 30 days after end of treatment
Safety Issue:
Description:MTD:defined as the dose level that can be given such that the estimated Dose limiting toxicity (DLT) probability is closest to approximately 25%.

Secondary Outcome Measures

Measure:Objective response rate (ORR) by RECIST 1.1
Time Frame:At the end of cycle 2 (- 7 days; each cycle is 21 days) and every 6 weeks thereafter, an average of 6 months.
Safety Issue:
Description:
Measure:Change from baseline in AhR target gene expression in whole blood after ex-vivo stimulation
Time Frame:Screening, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 4 Day 1(each cycle is 21 days)
Safety Issue:
Description:
Measure:Cytokine measurements, e.g. IL-6 (immunoassay), in whole blood after ex-vivo stimulation.
Time Frame:Screening, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 4 Day 1(each cycle is 21 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Non-small cell lung cancer (NSCLC)
  • Head and neck squamous cell carcinoma (HNSCC)
  • Colorectal cancer microsatellite stable (MSS)
  • Advanced cancer
  • Immunotherapy
  • Immuno oncology
  • Aryl Hydrocarbon Receptor inhibitor(AhRi)
  • Aryl Hydrocarbon Receptor

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