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

NCT04999202 | Terminated Phase 1 FDA Drug

• 4 other identifiers: 21343PN-A612023-503547-33-002020-003547-28
• Study Type: interventional
• Target: 47
• Locations: 4 countries
• Sites: 14

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 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.

Conditions

Advanced Solid Tumors

Keywords

Non-small cell lung cancer (NSCLC); Head and neck squamous cell carcinoma (HNSCC); Urothelial Cancer; Advanced cancer; Immunotherapy; Immuno oncology; Aryl Hydrocarbon Receptor inhibitor(AhRi); Aryl Hydrocarbon Receptor; Pembrolizumab; aPD1; Checkpoint inhibitor

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (5)

• Cmax of BAY2416964 after single-dose in Cycle 1

  Cycle 1 Day 1 (1 cycle is 21 days)

• Cmax of BAY2416964 after multiple-dose in Cycle 1

  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

  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

  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)

  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

Study Arms (2)

Dose escalation of BAY2416964

EXPERIMENTAL

Six dose levels of BAY 2416964 (as determined in the first in human mono-therapy study of BAY2416964) are planned in combination with standard dose Pembrolizumab.

Drug: BAY2416964; Drug: Pembrolizumab

Dose expansion of BAY2416964 in tumor type specific cohort

EXPERIMENTAL

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.

Drug: BAY2416964; Drug: Pembrolizumab

Interventions

BAY2416964 DRUG

Oral, twice or three times daily

Dose escalation of BAY2416964

Pembrolizumab DRUG

Administered as a dose of 200 mg using a 30-minute IV infusion every 3 weeks

Dose escalation of BAY2416964; Dose expansion of BAY2416964 in tumor type specific cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (14)

Florida Cancer Specialists

Altamonte Springs, Florida, 32701, United States

Location

Florida Cancer Specialists & Research Institute

Sarasota, Florida, 34232, United States

Location

Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit

Detroit, Michigan, 48202, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology- Austin Midtown

Austin, Texas, 78705, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Sperimentazioni Cliniche

Napoli, Campania, 80131, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1

Milan, Lombardy, 20133, Italy

Location

Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative

Milan, Lombardy, 20141, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20162, Italy

Location

Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia

Rozzano, Lombardy, 20089, Italy

Location

National University Hospital Medical Centre

Singapore, 119074, Singapore

Location

Belfast City Hospital

Belfast, North Ireland, BT12 7AB, United Kingdom

Location

Freeman Hospital

Newcastle, Tyne and Wear, NE7 7DN, United Kingdom

Location

Related Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 10, 2021
• Study Start: August 30, 2021
• Primary Completion: June 28, 2024
• Study Completion: January 20, 2025
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1); US (6); IT (5); GB (2)