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A Study to Learn How Safe the Study Drug BAY 2416964 (AhR Inhibitor) in Combination With the Treatment Pembrolizumab is, How This Combination Affects the Body, the Maximum Amount That Can be Given, How it Moves Into, Through and Out of the Body and Its Action Against Advanced Solid Cancers in Adults

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ClinicalTrials.gov Identifier: NCT04999202
Recruitment Status : Recruiting
First Posted : August 10, 2021
Last Update Posted : September 14, 2022
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE August 5, 2021
First Posted Date  ICMJE August 10, 2021
Last Update Posted Date September 14, 2022
Actual Study Start Date  ICMJE August 30, 2021
Estimated Primary Completion Date March 20, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2021)
  • The incidence of TEAEs including TESAEs [ Time Frame: After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab ]
    TEAEs: treatment-emergent adverse events TESAEs: treatment-emergent serious adverse events
  • The severity of TEAEs including TESAEs [ Time Frame: After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab ]
  • Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2416964 [ Time Frame: Cycle 1 (21 days) in dose escalation ]
    The MTD/MAD is the dose level that can be safely given, defined as the occurrence of dose-limiting toxicities (DLTs) below a certain threshold.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2022)
  • Cmax of BAY2416964 after single-dose in Cycle 1 [ Time Frame: Cycle 1 Day 1 (1 cycle is 21 days) ]
  • Cmax of BAY2416964 after multiple-dose in Cycle 1 [ Time Frame: Cycle 1 Day 15 (1 cycle is 21 days) ]
  • AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after single-dose in Cycle 1 [ Time Frame: Cycle 1 Day 1 (1 cycle is 21 days) ]
  • AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after multiple-dose in Cycle 1 [ Time Frame: Cycle 1 Day 15 (1 cycle is 21 days) ]
  • Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) [ Time Frame: At the end of Cycle 2 (-7 days, each cycle is 21 days), Cycle 4 (-7 days) and every 9 weeks (-7 days) thereafter ]
    ORR will be evaluated using RECIST 1.1 by investigator assessment.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2021)
  • Cmax of BAY2416964 after single-dose in Cycle 1 [ Time Frame: Cycle 1 Day 1 (1 cycle is 21 days) ]
  • Cmax of BAY2416964 after multiple-dose in Cycle 1 [ Time Frame: Cycle 1 Day 15 (1 cycle is 21 days) ]
  • AUC(0-12) of BAY2416964 after single-dose in Cycle 1 [ Time Frame: Cycle 1 Day 1 (1 cycle is 21 days) ]
  • AUC(0-12) of BAY2416964 after multiple-dose in Cycle 1 [ Time Frame: Cycle 1 Day 15 (1 cycle is 21 days) ]
  • Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) [ Time Frame: At the end of Cycle 2 (- 7 days, each cycle is 21 days) and every 6 weeks thereafter ]
    ORR will be evaluated using RECIST 1.1 by investigator assessment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Learn How Safe the Study Drug BAY 2416964 (AhR Inhibitor) in Combination With the Treatment Pembrolizumab is, How This Combination Affects the Body, the Maximum Amount That Can be Given, How it Moves Into, Through and Out of the Body and Its Action Against Advanced Solid Cancers in Adults
Official Title  ICMJE An Open-label, Phase 1b, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics and Efficacy of the Aryl Hydrocarbon Receptor Inhibitor (AhRi) BAY 2416964 in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
Brief Summary

Researchers are looking for a better way to treat advanced solid cancers including head and neck cancer, lung cancer and bladder cancer.

In some people with cancer a protein called Aryl Hydrocarbon Receptor (AhR) can prevent immune cells from fighting tumor cells. The study drug, BAY 2416964, is a small molecule which blocks the AhR allowing the body to use its immune response against the cancer cells. Researchers think that BAY 2416964 given together with a cancer treatment called pembrolizumab may help shrink tumors in people with cancer.

The main aims of this study are to find for BAY 2416964 in combination with pembrolizumab,

  • how safe this drug combination is
  • how it affects the body (also referred to as tolerability)
  • the highest amount of BAY 2416964 that can be given in combination with pembrolizumab without too many side effects.

The researchers will also study the action of BAY 2416964 in combination with pembrolizumab against the cancer.

The participants in this study will get BAY 2416964 and pembrolizumab. BAY 2416964 will be given in tablet form by mouth. Pembrolizumab will be given as an intravenous (IV) infusion. An IV infusion is given through a needle into a vein.

This study will have two parts. The first part will help find the most appropriate dose that can be given in the second part.

Each participant of the first, so called dose escalation part, will be assigned to one specific dose group for BAY 2416964. The amount of BAY 2416964 that is given increases step-wise from one group to the next. The dose of pembrolizumab will always be the same.

The participants of the second, so called dose expansion part, will receive the most appropriate dose of BAY 2416964 found in the first part.

During the study, the participants will receive the treatment in 3-week periods called cycles. In each cycle, the participants will in general get pembrolizumab once and BAY 2416964 in a daily schedule. These 3-week cycles will be repeated throughout the trial. The participants can take the study treatment until their cancer gets worse, until they have medical problems, or until they leave the trial. Participants will have around 4 visits in each cycle. Some of the visits can also be done via phone.

During the study, the study doctors and their team will:

  • take blood and urine samples
  • check if the participants' cancer has spread using computed tomography scans or magnetic resonance imaging scans of the participants' tumors
  • check the participants' overall health
  • ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: BAY2416964
    Oral, twice daily in dose level 1 and dose level 2, three times daily in dose level 3 and dose level 4.
  • Drug: BAY2416964
    Oral, the highest dose determined safe in combination with pembrolizumab in the dose escalation part.
  • Drug: Pembrolizumab
    Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks
Study Arms  ICMJE
  • Experimental: Dose escalation of BAY2416964
    Up to four dose levels of BAY2416964 (as determined in the first in human mono-therapy study of BAY2416964) will be given in combination with standard dose Pembrolizumab.
    Interventions:
    • Drug: BAY2416964
    • Drug: Pembrolizumab
  • Experimental: Dose expansion of BAY2416964 in tumor type specific cohort
    To determine the RP2D of BAY2416964 in combination therapy with pembrolizumab. Participants will be enrolled in up to 3 tumor type-specific cohorts including relapsed/refractory non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) and urothelial cancer.
    Interventions:
    • Drug: BAY2416964
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 5, 2021)
78
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 20, 2024
Estimated Primary Completion Date March 20, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 clinically meaningful benefit, or are intolerant to treatment, or refuse standard treatment. Note: there is no limit to the number of prior treatment regimens.

    • Dose Escalation: all solid tumor types
    • Tumor type-specific Expansion cohorts:

      • NSCLC
      • HNSCC
      • Urothelial Cancer
  • Participants must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.
  • Have measurable disease per RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion Criteria:

  • Severe (Common terminology criteria for adverse events (CTCAE) v.5 Grade ≥ 3) infections within 4 weeks before the first study intervention administration
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy
  • Has active Central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Cardiac disease as specified in the protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com
Listed Location Countries  ICMJE Italy,   Singapore,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04999202
Other Study ID Numbers  ICMJE 21343
PN-A61 ( Other Identifier: Merck )
2020-003547-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.
Current Responsible Party Bayer
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Bayer
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP