check_circleStudy Completed

Advanced solid tumors

A First-in-Humans dose finding study for an Aryl Hydrocarbon Receptor Inhibitor (AhRi) in patients with advanced cancer

Trial 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.

Key Participants Requirements

Sex

All

Age

18 - N/A

Trial summary

Enrollment Goal
78
Trial Dates
August 2019 - January 2024
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY2416964
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
University of Texas MD Anderson Cancer CenterHouston, 77030, United States
Completed
START | San AntonioSan Antonio, 78229, United States
Completed
Greenville Health SystemGreenville, 29605, United States
Completed
Yale University School of MedicineNew Haven, 06510, United States
Completed
Royal Marsden NHS Trust (Surrey)Sutton, SM2 5PT, United Kingdom
Completed
Universitätsklinikum HeidelbergHeidelberg, 69115, Germany
Completed
Hospital Universitario 12 de OctubreMadrid, 28041, Spain
Completed
Hospital Ramón y Cajal | OncologíaMadrid, 28034, Spain
Completed
Hospital Clínico Universitario de ValenciaValencia, 46010, Spain
Completed
Institut Català d'Oncologia HospitaletHospitalet de Llobregat, 08907, Spain
Withdrawn
Cancer Hospital, Chinese Academy of Medical SciencesBeijing, 100000, China
Completed
Beatson West of Scotland Cancer CentreGlasgow, G12 0YN, United Kingdom
Completed
Christie HospitalManchester, M20 4BX, United Kingdom
Completed
Princess Margaret Hospital-University Health NetworkToronto, M5G 2M9, Canada
Withdrawn
Cross Cancer InstituteEdmonton, T6G 1Z2, Canada
Completed
CHU de Québec-Université LavalQuebec, G1R 2J6, Canada
Completed
Universitätsklinikum Carl Gustav Carus an der Technischen Universität DresdenDresden, 1307, Germany
Completed
Charité Campus Benjamin Franklin (CBF)Berlin, 12203, Germany
Completed
Hospital Universitario Virgen de la Victoria | Cardiology DepartmentMalaga, 29010, Spain
Withdrawn
Marienhospital Herne UniversitätsklinikHerne, 44625, Germany

Primary Outcome

  • The incidence of treatment emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs) and dose-limiting toxicities (DLTs)
    date_rangeTime Frame:
    Up to 90 days after end of treatment
  • Severity of treatment emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs) and dose-limiting toxicities (DLTs)
    date_rangeTime Frame:
    Up to 90 days after end of treatment
  • Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2416964
    MTD:defined as the dose level that can be given such that the estimated Dose limiting toxicity (DLT) probability is closest to approximately 25%.
    date_rangeTime Frame:
    Cycle 1 (21 days) in dose escalation
  • Recommended Phase II dose (RP2D) of BAY2416964
    Integration of all available safety, PK and PD data
    date_rangeTime Frame:
    Up to 90 days after end of treatment
  • Maximal plasma exposure (Cmax) for once daily (QD) dosing of BAY2416964 after single-dose and multiple-dose in Cycle 1.
    date_rangeTime Frame:
    From pre-dose up to 24 hours after administration on Cycle 1 (21 days) Day 1. From pre-dose up to 12 hours after administration on Cycle 1 (21 days) Day 15
  • Area under the curve [AUC (0 – t)] (t=6,12 or 24 dependent on the dosing regimen) of BAY2416964 after single and multiple-dose in Cycle 1
    date_rangeTime Frame:
    From pre-dose up to 6, 12, or 24 hours after administration on Day 1 and/or Day 15 in Cycle 1 (21 days).

Secondary Outcome

  • Objective response rate (ORR) by RECIST 1.1
    date_rangeTime Frame:
    At the end of Cycle 2 (- 7 days), Cycle 4 (-7 days), every 9 weeks (- 7 days) from Cycle 5 to Cycle 10 and every 4th cycle (- 7 days) from Cycle 11 onwards. Each cycle is 21 days.
  • Change from baseline in AhR target gene expression in whole blood after ex-vivo stimulation
    date_rangeTime Frame:
    Screening, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 4 Day 1(each cycle is 21 days)
  • Cytokine measurements, e.g. IL-6 (immunoassay), in whole blood after ex-vivo stimulation.
    date_rangeTime Frame:
    Screening, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 4 Day 1(each cycle is 21 days)

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Sequential Assignment
Trial Arms
2