BAY3375968 + Pembrolizumab for Advanced Cancer

Not currently recruiting at 56 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bayer

Must be taking: PD-1/PD-L1 inhibitors

Must not be taking: Chronic steroids, others

Disqualifiers: Active malignancy, CNS malignancy, others

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

Compensation: Varies

Number of Visits: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with advanced solid tumors, which are cancers that have spread and resist existing treatments. The study examines a drug called BAY3375968, which targets cells that weaken the immune system. It tests the drug alone and with pembrolizumab, an immunotherapy drug, to determine if it enhances the body's ability to fight cancer. Researchers aim to assess the safety and effectiveness of these treatments and identify the optimal dose. Individuals with specific cancers, such as lung, breast, head and neck, gastric cancer, or melanoma, who have not responded well to other treatments, may be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the study team to understand any potential interactions or requirements.

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

Research has shown that BAY3375968, an antibody targeting a protein on certain immune cells, has been effective in animal studies. However, specific safety information for BAY3375968 in humans is not yet available. This study is in its first phase, primarily aiming to determine the treatment's safety for people. Researchers are assessing how well participants tolerate it and identifying potential side effects.

Pembrolizumab, a PD-1 inhibitor, is already approved for treating some cancers, providing more safety information. It is generally considered safe, but like any medication, it can have side effects. These will be closely monitored in this study when used with BAY3375968.

In summary, while pembrolizumab has a known safety record, BAY3375968 is new and is being tested for safety in humans for the first time in this study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BAY3375968 because it offers a novel approach for treating advanced cancers, especially those resistant to immune checkpoint inhibitors (ICIs). Unlike existing therapies, BAY3375968 is being tested both as a monotherapy and in combination with pembrolizumab, potentially enhancing its effectiveness against tough-to-treat tumors like NSCLC, TNBC, HNSCC, and melanoma. This treatment stands out due to its unique mechanism of action, which aims to overcome resistance to previous ICI therapies, offering new hope for patients who have limited options.

What evidence suggests that BAY3375968 and pembrolizumab could be effective for advanced solid tumors?

Research shows that BAY3375968 targets a protein called CCR8 on certain immune cells, aiding the immune system in fighting cancer. Animal studies have demonstrated promise by reducing these suppressive cells and enhancing the effects of existing cancer treatments like PD-1 inhibitors. In this trial, some participants will receive BAY3375968 combined with pembrolizumab, a PD-1 inhibitor, potentially providing extra benefits by further enhancing the immune response. Pembrolizumab alone has already improved survival rates in some cancers, such as lung cancer and melanoma. These findings suggest that the combination could be more effective against advanced solid tumors. Other participants will receive BAY3375968 as monotherapy, which is also under evaluation for its potential effectiveness. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have spread and are not curable with existing treatments. Participants must be physically capable of daily activities (ECOG PS 0 or 1), have functioning organs, agree to use contraception if applicable, and not be pregnant or breastfeeding. They should have tried all other effective treatments without success.

Inclusion Criteria

Willingness and medical feasibility (as per Investigator assessment) to undergo paired tumor biopsies with a non-significant risk

I've tried or can't tolerate all known beneficial treatments.

I have been diagnosed with TNBC, NSCLC, HNSCC, or melanoma.

Exclusion Criteria

Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Any other history, condition, therapy, or uncontrolled intercurrent illness which could in the opinion of the Investigator affect compliance with study requirements

My cancer originated in my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

2 visits (in-person)

Dose Escalation

Participants receive increasing doses of BAY3375968 alone or in combination with pembrolizumab to determine the best dose

Varies per participant

5 visits per week in the first treatment week, 1-3 visits per month thereafter

Dose Expansion

Participants receive the best dose of BAY3375968 alone or in combination with pembrolizumab found in the dose escalation phase

Varies per participant

1-3 visits per month

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

1 visit (in-person) within 30 days after last treatment, health check via phone call

Long-term Follow-up

Participants' cancer status and survival are checked every 12 weeks until cancer progression or new therapy, and every 6 months for up to 24 months after the last participant left the study

Up to 24 months

Phone calls every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• BAY3375968
• Pembrolizumab

Trial Overview The study tests BAY3375968 alone and combined with Pembrolizumab in two parts: dose escalation to find the safest high dose, then dose expansion at this best dose focusing on lung, breast, head/neck cancer, and melanoma. It measures safety, tolerability, how the body processes the drug, optimal dosing levels, and anti-cancer effects.

How Is the Trial Designed?

Group I: Dose expansion - Arm 2B Experimental Treatment 2 Interventions

Disease-specific combination expansion with separate cohorts in ICI-relapsed tumor types (NSCLC, TNBC, HNSCC, gastric cancer, or melanoma)

Group II: Dose expansion - Arm 2A Experimental Treatment 1 Intervention

BAY3375968 monotherapy-mode-of-action (monotherapy-MoA) expansion in subjects with one of the following tumor types: NSCLC, TNBC, HNSCC, or melanoma. The tumors should have primary (ICI-refractory) or secondary (ICI-relapsed) resistance to prior ICI-therapy. The final decision on the enrolled tumor type is at the discretion of the Sponsor.

Group III: Dose escalation - Arm 1B Experimental Treatment 2 Interventions

Dose escalation of BAY 3375968 in combination with pembrolizumab

Group IV: Dose escalation - Arm 1A Experimental Treatment 1 Intervention

Dose escalation of BAY3375968 as monotherapy

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 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]

In the KEYNOTE-010 study involving patients with advanced NSCLC, pembrolizumab significantly improved health-related quality of life (HRQoL) scores compared to docetaxel, indicating better overall patient well-being during treatment.

Patients treated with pembrolizumab experienced less deterioration in symptoms like cough and dyspnea, and showed a significant prolongation in time to deterioration for these symptoms, particularly at the 10 mg/kg dose compared to docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1-Expressing NSCLC. Barlesi, F., Garon, EB., Kim, DW., et al.[2020]

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, 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]

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 (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]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05537740

NCT05537740 | A First-in-human Study to Learn How Safe ... The study treatment BAY3375968 is an antibody that binds to a protein called CCR8 which is located on the surface of regulatory T cells.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11164760/

Selective depletion of tumor-infiltrating regulatory T cells with ... We developed BAY 3375968, a novel anti-human CCR8 antibody, along with respective surrogate anti-mouse CCR8 antibodies, and demonstrated their in vitro mode-of ...

3. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/2866/704369/Abstract-2866-BAY-3375968-An-afucosylated-anti

BAY 3375968: An afucosylated anti-CCR8 antibody depleting ... CCR8+ Tregs are associated with high tumor grade and poor overall survival across many tumor types such as lung, breast, or head-neck cancer.

4. trials.teamjackfoundation.org trials.teamjackfoundation.org/trials/NCT05537740

A First-in-human Study to Learn How Safe the ... - Clinical Trial Finder Animal studies also showed that BAY3375968 may add more anti-cancer effect to immunotherapy with PD-1/PD-L1 inhibitors when used in combination. All of these ...

5. clinconnect.io clinconnect.io/trials/NCT05537740

A First-in-human Study to Learn How Safe the Study Drug Researchers want to find the best dose of BAY3375968 and understand its effects on the body, including any potential side effects. This study is important ...

6. withpower.com withpower.com/trial/phase-1-solid-tumors-advanced-solid-tumors-8-2022-f06fc

BAY3375968 + Pembrolizumab for Advanced Cancer Rarely, it can lead to type 1 diabetes. There is no specific safety data available for BAY3375968.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10965

A First-in-human Study to Learn How Safe the Study Drug ... The study treatment BAY3375968 is an antibody that binds to a protein called CCR8 which is located on the surface of regulatory T cells.