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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04999202
• Other study ID #: 21343
• Secondary ID: PN-A612023-50354
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 30, 2021
• Est. completion date: March 14, 2025

Study information

• Verified date: June 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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 changes 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 changed in size 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: March 14, 2025
• Est. primary completion date: March 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• Dose Escalation: all solid tumor types

• Tumor type-specific Expansion cohorts:

• NSCLC

• HNSCC with primary location in oropharynx, oral cavity, hypopharynx or larynx

• 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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• BAY2416964
Oral, twice or three times daily
• BAY2416964
The highest dose determined safe in combination with pembrolizumab in the dose escalation part or a lower dose. More than one dose may be explored in the dose expansion.
• Pembrolizumab
Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)	Milano	Lombardia
Italy	Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione G.Pascale	Napoli	Campania
Singapore	National University Hospital	Singapore
United Kingdom	Belfast City Hospital	Belfast	North Ireland
United Kingdom	Freeman Hospital	Newcastle	Tyne And Wear
United States	Florida Cancer Specialists	Altamonte Springs	Florida
United States	Texas Oncology- Austin Midtown	Austin	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Florida Cancer Specialists & Research Institute	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Italy,  Singapore,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of TEAEs including TESAEs	TEAEs: treatment-emergent adverse events TESAEs: treatment-emergent serious adverse events	After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
Primary	The severity of TEAEs including TESAEs		After first administration of BAY2416964 in combination with pembrolizumab up to 90 days after the last dose of BAY2416964 in combination with pembrolizumab
Primary	Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2416964	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.	Cycle 1 (21 days) in dose escalation
Secondary	Cmax of BAY2416964 after single-dose in Cycle 1		Cycle 1 Day 1 (1 cycle is 21 days)
Secondary	Cmax of BAY2416964 after multiple-dose in Cycle 1		Cycle 1 Day 15 (1 cycle is 21 days)
Secondary	AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after single-dose in Cycle 1		Cycle 1 Day 1 (1 cycle is 21 days)
Secondary	AUC(0-t) (t depend on the dosing regimen) of BAY2416964 after multiple-dose in Cycle 1		Cycle 1 Day 15 (1 cycle is 21 days)
Secondary	Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)	ORR will be evaluated using RECIST 1.1 by investigator assessment.	At the end of Cycle 2 (-7 days, each cycle is 21 days), Cycle 4 (-7 days) and at the end of every third cycle (-7 days) from Cycle 5 onwards

External Links

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