BAY3375968 + Pembrolizumab for Advanced Cancer

Recruiting at 39 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new antibody treatment, BAY3375968, for people with advanced cancers. The treatment aims to improve the immune system's ability to fight cancer by reducing specific cells that suppress immune response. Researchers will study its safety, the best dose, and how well it works alone and with another cancer drug, pembrolizumab.

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.

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?

Pembrolizumab has been shown to improve survival in patients with advanced non-small cell lung cancer and melanoma, especially when tumors express certain proteins (PD-L1). It has been approved for use in these cancers after demonstrating better outcomes compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of BAY3375968 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in cancer treatment and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as inflammation of the lungs, liver, or thyroid. Rarely, it can lead to type 1 diabetes. There is no specific safety data available for BAY3375968. ^{1 2 5 6 7}

What makes the drug combination of BAY3375968 and Pembrolizumab unique for treating advanced cancer?

This treatment combines BAY3375968 with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells by blocking a pathway that tumors use to hide from immune cells. Pembrolizumab has shown effectiveness in various cancers, and combining it with BAY3375968 may enhance its ability to fight advanced cancer. ^{1 2 7 8 9}

Research Team

Eligibility Criteria

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

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

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

My cancer originated in my brain or spinal cord.

Trial Timeline

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

Treatment Details

Interventions

• BAY3375968 (Monoclonal Antibodies)
• Pembrolizumab (PD-1 Inhibitor)

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.

Participant Groups

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

Findings from Research

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) 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]

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]

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 (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, 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 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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

4. United States 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. [2020]

5. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]