BAY 2416964 + Pembrolizumab for Cancer

No longer recruiting at 29 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bayer

Disqualifiers: Severe infections, Active autoimmune, Immunodeficiency, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced solid cancers, such as head and neck, lung, and bladder cancers. Researchers aim to determine if the experimental drug BAY 2416964, combined with the existing cancer drug pembrolizumab, can enhance the body's ability to fight cancer by inhibiting a protein that blocks immune cells. The trial will assess the safety of the drug combination, its effects on the body, and the optimal dose that minimizes side effects. Individuals who have tried other treatments and whose cancers have progressed may be suitable candidates for this study. Participants will take BAY 2416964 orally and receive pembrolizumab through an IV, with doctors monitoring their health and cancer response. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific situation with the study doctors.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of BAY 2416964 and pembrolizumab has been tested for safety in cancer patients. In a study with 72 participants, the treatment was generally well-tolerated. About 33% of patients experienced moderate side effects, but no severe complications or deaths related to the treatment occurred. These findings suggest that most patients can handle the combination. It is important to note that these results come from early research focused on safety. Further studies will explore how this treatment affects cancer and determine the best doses to use. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cancer?

Researchers are excited about BAY2416964 combined with pembrolizumab because it offers a novel approach to fighting cancer. While pembrolizumab is a well-established immunotherapy that helps the immune system recognize and attack cancer cells, BAY2416964 introduces a new mechanism by potentially enhancing the immune response further. This combination targets specific cancer types like non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and urothelial cancer, which might improve outcomes for patients who have relapsed or are resistant to existing treatments. By working together, these drugs might boost the body’s ability to combat cancer more effectively than current therapies alone.

What evidence suggests that this trial's treatments could be effective for advanced solid cancers?

Research shows that BAY 2416964 blocks a protein called Aryl Hydrocarbon Receptor (AhR), which can help the immune system attack cancer cells. Early studies in humans and mice indicate that this treatment can increase immune cell activity. This trial will study BAY 2416964 in combination with Pembrolizumab, a proven cancer treatment that helps the immune system identify and fight cancer cells. Pembrolizumab is approved for several cancers, including some types of lung and head and neck cancers. Together, these treatments aim to shrink tumors by boosting the body's natural defenses against cancer. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including specific types of lung, bladder, and head and neck cancer that have worsened after standard treatments or who cannot tolerate such treatments. Participants must be over 18 years old with an ECOG performance status of 0 to 1 (indicating they are fully active or restricted in physically strenuous activity but ambulatory).

Inclusion Criteria

My advanced cancer has not responded to, or I cannot tolerate, all known beneficial treatments.

My cancer is a solid tumor type.

My cancer has worsened despite treatment with specific immune therapy.

Exclusion Criteria

I have or had lung inflammation that needed steroids.

I have a heart condition as described in the study details.

I have not had a severe infection in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants are assigned to specific dose groups for BAY 2416964, with doses changing step-wise. Pembrolizumab dose remains constant.

21 days per cycle

4 visits per cycle (in-person and phone)

Dose Expansion

Participants receive the most appropriate dose of BAY 2416964 found in the dose escalation phase.

21 days per cycle

4 visits per cycle (in-person and phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events tracking.

Up to 90 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• BAY2416964
• Pembrolizumab

Trial Overview The trial is testing BAY 2416964 combined with pembrolizumab for safety, tolerability, the maximum safe dose level, how it affects the body and its effectiveness against cancer. The study has two parts: dose escalation to find the right dose and dose expansion using this determined dose.

How Is the Trial Designed?

Group I: Dose expansion of BAY2416964 in tumor type specific cohort Experimental Treatment 2 Interventions

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.

Group II: Dose escalation of BAY2416964 Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (P) can be safely combined with various chemotherapy agents, including gemcitabine and liposomal doxorubicin, in patients with advanced solid tumors, as shown in a phase Ib trial involving 49 patients.

The combination treatment resulted in eight partial responses across different tumor types, indicating potential efficacy, but further studies are needed to confirm if the response duration is better than chemotherapy or immunotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Weiss, GJ., Waypa, J., Blaydorn, L., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.2502

Initial results from a first-in-human, phase I study of ... BAY2416964 is a novel, potent, oral AhR inhibitor (AhRi) that antagonizes AhR ligand-induced immunosuppressive effects, resulting in enhanced proinflammatory ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04999202

A Study to Learn How Safe the Study Drug BAY 2416964 ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10649913/

Targeting the aryl hydrocarbon receptor (AhR) with BAY ... Nuclear translocation, target engagement and the effect of BAY 2416964 on agonist-induced AhR activation were assessed in human and mouse cancer ...

4. mdanderson.org mdanderson.org/cancerwise/clinical-trial-of-new-ahr-inhibitor-shows-cancer-might-be-even-more-wily-than-we-thought.h00-159619434.html

Clinical trial of new AhR inhibitor shows cancer might be ... A Phase I clinical trial of a drug called BAY 2416964 that can block AhR. As a result, it should increase the activity of antigen-presenting cells and T cells.

5. jitc.bmj.com jitc.bmj.com/content/11/11/e007495

Targeting the aryl hydrocarbon receptor (AhR) with BAY ... Nuclear translocation, target engagement and the effect of BAY 2416964 on agonist-induced AhR activation were assessed in human and mouse cancer ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2502

Initial results from a first-in-human, phase I study of ... Results: As of November 4, 2022, 72 patients had been treated with BAY2416964: 39 patients in dose escalation and 33 patients in the initial ...

7. clinicaltrials.bayer.com clinicaltrials.bayer.com/study/21343

Advanced solid tumors | Study 21343 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 ...

8. withpower.com withpower.com/trial/phase-1-7-2021-1e713

BAY 2416964 + Pembrolizumab for Cancer The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that ...