NCT04999202

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

Terminated Phase 1 Last updated 10 February 2025

What this trial tests

Phase 1 trial testing BAY2416964 in Advanced Solid Tumors in 47 participants. Terminated before completion.

Timeline

30 August 2021

Primary endpoint
28 June 2024

20 January 2025

Quick facts

Lead sponsor	Bayer
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	47
Start date	30 August 2021
Primary completion	28 June 2024
Estimated completion	20 January 2025
Sites	14 locations across Italy, Singapore, United Kingdom, United States

Drugs / interventions tested

• BAY2416964 — full drug profile →
• BAY2416964 — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Advanced Solid Tumors — all drugs for Advanced Solid Tumors →

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Indoleamine 2,3-dioxygenase (IDO) inhibitors and cancer immunotherapy.
   Fujiwara Y, Kato S, Nesline MK, Conroy JM, et al · · 2022 · cited 222× · PMID 36058143 · DOI 10.1016/j.ctrv.2022.102461
2. Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.
   Yang L, Chu Z, Liu M, Zou Q, et al · · 2023 · cited 198× · PMID 37277776 · DOI 10.1186/s13045-023-01453-1
3. Targeting Tryptophan Catabolism in Cancer Immunotherapy Era: Challenges and Perspectives.
   Peyraud F, Guegan JP, Bodet D, Cousin S, et al · · 2022 · cited 94× · PMID 35173722 · DOI 10.3389/fimmu.2022.807271
4. Metabolic reprogramming in colorectal cancer: regulatory networks and therapy.
   Zhang J, Zou S, Fang L. · · 2023 · cited 42× · PMID 36755301 · DOI 10.1186/s13578-023-00977-w
5. The aryl hydrocarbon receptor: a rehabilitated target for therapeutic immune modulation.
   Polonio CM, McHale KA, Sherr DH, Rubenstein D, et al · · 2025 · cited 41× · PMID 40247142 · DOI 10.1038/s41573-025-01172-x
6. Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment.
   Johnson RL, Cummings M, Thangavelu A, Theophilou G, et al · · 2021 · cited 33× · PMID 34944851 · DOI 10.3390/cancers13246231
7. The kynurenine pathway in HIV, frailty and inflammaging.
   Sultana S, Elengickal A, Bensreti H, Belin de Chantemèle E, et al · · 2023 · cited 27× · PMID 37744363 · DOI 10.3389/fimmu.2023.1244622
8. Review of Current and Future Medical Treatments in Head and Neck Squamous Cell Carcinoma.
   Lee AM, Weaver AN, Acosta P, Harris L, et al · · 2024 · cited 17× · PMID 39456583 · DOI 10.3390/cancers16203488