BAY2965501 + Pembrolizumab for Advanced Cancer

Not currently recruiting at 48 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bayer

Must be taking: Platinum chemotherapy

Must not be taking: Anti-PD-1 agents

Disqualifiers: Brain metastases, CNS malignancy, others

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

Compensation: Varies

Number of Visits: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks a better way to treat advanced solid tumors, which are cancers that have spread and resist current treatments. Researchers are testing a new drug, BAY2965501, both alone and with other treatments, to determine if it can help the immune system fight cancer. The trial will assess the safety and effectiveness of different doses of BAY2965501 and their impact on tumors. Individuals with specific cancers, such as certain skin, kidney, stomach, and lung cancers, who have not responded to standard treatments, might be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that previous therapy with certain DGK inhibitors is prohibited, and there are specific criteria for participants who have received certain types of cancer treatments before. It's best to discuss your current medications with the study team to get a clear answer.

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

Research shows that BAY2965501 is currently being tested for human safety. Specific information on its tolerability remains limited. However, pembrolizumab, used alongside BAY2965501 in this trial, has been extensively studied and is generally well-tolerated in other cancer treatments.

As this trial begins, the primary goal is to determine the safest dose and identify any potential side effects. The full safety profile of BAY2965501 is still under investigation. Progression to later trial stages would indicate that initial safety results were acceptable. Prospective participants should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BAY2965501 in combination with pembrolizumab because it takes a novel approach to treating advanced cancers like non-small cell lung cancer (NSCLC) and gastric adenocarcinoma. Unlike standard treatments that typically target cancer cells broadly, BAY2965501 is designed to enhance the immune system's ability to fight cancer by potentially targeting specific pathways not addressed by existing therapies. This combination with pembrolizumab, a well-known immunotherapy, aims to boost the immune response even further, possibly leading to more effective control of tumor growth. Additionally, the inclusion of a platinum-based regimen in one of the trial arms may offer synergistic effects, potentially improving outcomes for patients with these tough-to-treat cancers.

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

Research has shown that BAY2965501 blocks a specific enzyme in T-cells, immune cells that can attack cancer. In lab studies, BAY2965501 enabled T-cells and natural killer cells to kill more cancer cells. This suggests that BAY2965501 might strengthen the body's natural defenses against tumors. In this trial, participants will receive BAY2965501 with pembrolizumab, a current cancer treatment, to potentially enhance its effectiveness, as pembrolizumab is known to help the immune system fight cancer. Although these findings are early, they provide a hopeful basis for further testing in people with advanced cancers. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including specific types of skin, kidney, stomach, and lung cancers. Participants must have a confirmed diagnosis, measurable disease per RECIST 1.1 criteria, adequate organ function, and an ECOG status of 0 to 1. They cannot have had certain recent treatments or severe infusion reactions to similar drugs in the past.

Inclusion Criteria

Have measurable disease per Response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) as assessed by the local site investigator

Participants with histologically confirmed diagnosis of a solid tumor will be enrolled onto this study: Dose escalation - All solid cancers, except primary central nervous system cancers; Monotherapy expansion cohorts - Non-small cell lung cancer (NSCLC), Gastric/Gastroesophageal Junction (GEJ) adenocarcinoma; BAY 2965501 and pembrolizumab combination expansion cohorts - NSCLC participants with tumors that are TPS score ≥50% PDL-1 high and eligible for standard of care anti-PD(L)-1 monotherapy in the first line incurable treatment setting

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have never been treated with a DGK inhibitor.

My cancer started in the brain or spinal cord.

I have a stomach or intestine condition that affects how my body absorbs medicine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Dose Escalation

Participants receive increasing doses of BAY2965501 as monotherapy or in combination with pembrolizumab and platinum-based chemotherapy to determine the most appropriate dose.

Several months

Regular visits for dose administration and monitoring

Dose Expansion

Participants receive the most appropriate dose of BAY2965501 determined from the dose escalation phase, either as monotherapy or in combination with pembrolizumab and platinum-based chemotherapy.

Several months

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with health checks and cancer progression assessments.

Every 12 weeks until disease progression or new therapy

Visits at 30 and 90 days post-treatment, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BAY2965501

Trial Overview The study tests BAY2965501 alone or combined with pembrolizumab on different tumor types. It aims to find safe doses and understand how the drug affects the body and cancer cells. The trial has two parts: dose escalation to determine appropriate dosing levels and dose expansion where those doses are given more broadly.

How Is the Trial Designed?

Group I: Dose expansion of BAY2965501 +pembrolizumab Experimental Treatment 1 Intervention

For expansion part, specific tumor types are recruited (non-small cell lung cancer (NSCLC) and gastric/gastroesophageal junction (GEJ) adenocarcinoma). BAY2965501 will be taken in combination with 200mg pembrolizumab every 3 weeks.

Group II: Dose expansion of BAY2965501 Experimental Treatment 1 Intervention

For expansion part, specific tumor types are recruited: NSCLC (non-small cell lung cancer).

Group III: Dose expansion of BAY 2965501 + pembrolizumab + platinum-based regimen Experimental Treatment 1 Intervention

Participants with selected (to be decided by the sponsor) advanced solid tumors will be recruited in a dose expansion cohort of BAY 2965501 with pembrolizumab and platinum-based regimen.

Group IV: Dose escalation of BAY2965501+pembrolizumab Experimental Treatment 1 Intervention

For escalation part different dose levels of BAY2965501 are planned in combination with 200mg pembrolizumab. BAY2965501 will be taken in combination with 200mg pembrolizumab every 3 weeks.

Group V: Dose escalation of BAY2965501 Experimental Treatment 1 Intervention

For escalation part, different dose levels of BAY2965501 are planned.

Group VI: Dose escalation of BAY 2965501 + pembrolizumab + platinum-based regimen Experimental Treatment 1 Intervention

The starting dose of BAY 2965501 with pembrolizumab for this combination will be no higher than one dose level below that shown to be safe in BAY 2965501 and pembrolizumab dose escalation. The doses of platinum-based regimen will be as per standard of care and given for a maximum of 6 cycles, in line with the current labeled dose. The dose of pembrolizumab will be 200 mg every 3 weeks, in line with the current labeled dose.

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, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab was found to be safe and well tolerated in a phase I study involving 20 patients with advanced solid tumors, with no dose-limiting toxicities observed at doses up to 10 mg/kg every 2 weeks.

The treatment demonstrated durable antitumor activity, with complete responses in two patients and stable disease in 15 others, indicating that a minimum effective dose for antitumor activity is 2 mg/kg every 3 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Patnaik, A., Kang, SP., Rasco, D., et al.[2022]

Pembrolizumab (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[2021]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, is generally well tolerated, but can lead to rare immune-mediated adverse effects such as pleuropericarditis, as seen in a case involving a 64-year-old female patient.

The patient was effectively treated with colchicine, furosemide, and methylprednisolone, leading to symptom improvement and a decision to discontinue pembrolizumab, after which she remained asymptomatic for six months, highlighting the importance of recognizing and managing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. Suarez, ZK., Finke, AC., Hospedales, E., et al.[2023]

Pembrolizumab is an effective cancer treatment that works by reactivating T cells, but it can lead to various immune-related adverse events, including rare cases of synovitis.

Healthcare providers should be vigilant about the potential for pembrolizumab-induced synovitis and act quickly to treat it to prevent lasting joint damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could knee inflammatory synovitis be induced by pembrolizumab? Mahmoud, F., Wilkinson, JT., Gizinski, A., et al.[2018]

An elderly male patient on pembrolizumab developed four autoimmune toxicities, including type 1 diabetes and pneumonitis, highlighting the risk of multiple immune-related adverse events associated with this treatment.

The case suggests that aging may increase susceptibility to these adverse effects, necessitating close monitoring and prompt management, including stopping the immunotherapy and using steroids for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. Kethireddy, N., Thomas, S., Bindal, P., et al.[2021]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

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]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05614102

NCT05614102 | A First-in-human Study to Learn How Safe ... The study treatment BAY2965501 is currently under development as monotherapy or in combination for the treatment of people with advanced solid tumors.

2. clinicaltrials.bayer.com clinicaltrials.bayer.com/ru/study/21948

Advanced solid tumors | Study 21948 BAY2965501 blocks an enzyme in T-cells to activate them. T-cells are a type of immune cell that are known to have an anti-cancer effect and BAY2965501 is a ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00733

A First-in-human Study to Learn How Safe the Study Drug ... The study treatment BAY2965501 is currently under development as monotherapy or in combination for the treatment of people with advanced solid tumors.

4. withpower.com withpower.com/trial/phase-1-neoplasms-10-2022-f7361

BAY2965501 + Pembrolizumab for Advanced Cancer This trial is testing a new drug called BAY2965501, alone or with pembrolizumab, for people with advanced cancers that are hard to treat.

5. researchgate.net researchgate.net/publication/371458260_Abstract_ND04_BAY_2965501_A_highly_selective_DGK-_z_inhibitor_for_cancer_immuno-therapy_with_first-in-class_potential

Abstract ND04: BAY 2965501: A highly selective DGK- ζ ... A FiH trial with BAY 2965501 in patients with advanced solid tumors including NSCLC, gastric/GEJ AdCa, ccRCC, and melanoma patients, is currently enrolling ...

6. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A1029

926 BAY 2965501: a highly selective DGK zeta inhibitor ... BAY 2965501 is a highly potent and selective, orally available DGKζ inhibitor. A first-in-human clinical trial of BAY 2965501 in solid tumors is currently ...

7. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/ND04/727035/Abstract-ND04-BAY-2965501-A-highly-selective-DGK

BAY 2965501: A highly selective DGK- ζ inhibitor for cancer ... A FiH trial with BAY 2965501 in patients with advanced solid tumors including NSCLC, gastric/GEJ AdCa, ccRCC, and melanoma patients, is ...

8. careacross.com careacross.com/clinical-trials/trial/NCT05614102

A First-in-human Study to Learn How Safe the Study Drug ... A first-in-human study to learn how safe the study drug BAY2965501 is, find the best dose (single drug & combination), how it affects the body.