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 : July 15, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors||Drug: BAY2416964 Drug: Pembrolizumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||78 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||August 30, 2021|
|Estimated Primary Completion Date :||March 20, 2024|
|Estimated Study Completion Date :||March 20, 2024|
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.
Oral, twice daily in dose level 1 and dose level 2, three times daily in dose level 3 and dose level 4.
Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks
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.
Oral, the highest dose determined safe in combination with pembrolizumab in the dose escalation part.
Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04999202
|Contact: Bayer Clinical Trials Contact||(+)1-888-84 firstname.lastname@example.org|
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|Sarasota, Florida, United States, 34232|
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|Milano, Lombardia, Italy, 20133|
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|Southampton, Hampshire, United Kingdom, SO16 6YD|
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|Bebington, Merseyside, United Kingdom, CH63 4JY|
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|Belfast, North Ireland, United Kingdom, BT12 7AB|
|Freeman Hospital||Not yet recruiting|
|Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN|