BAY2965501 + Pembrolizumab for Advanced Cancer

Recruiting at 36 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

284 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BAY2965501, alone or with pembrolizumab, for people with advanced cancers that are hard to treat. The drug helps the immune system fight cancer by activating certain immune cells. Researchers aim to find the safest and most effective dose and see how well it works against tumors. Pembrolizumab has shown efficacy in treating various cancers, including melanoma, cervical cancer, and head and neck cancer.

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.

What data supports the effectiveness of the drug BAY2965501 + Pembrolizumab for advanced cancer?

Pembrolizumab, one of the drugs in the combination, has shown promising results in treating advanced non-small cell lung cancer and melanoma, suggesting it can be effective in fighting certain types of cancer. ^{1 2 3 4 5}

What is known about the safety of BAY2965501 + Pembrolizumab for advanced cancer?

Pembrolizumab is generally well tolerated, with common side effects including tiredness, rash, itching, and diarrhea. Some people may experience less common immune-related side effects like inflammation of the lungs, liver, or thyroid, and other rare conditions. There is no specific safety data available for BAY2965501, but pembrolizumab has been studied extensively. ^{6 7 8 9 10}

What makes the drug BAY2965501 + Pembrolizumab unique for advanced cancer?

BAY2965501 combined with Pembrolizumab is unique because it pairs a new investigational drug (BAY2965501) with Pembrolizumab, an established immunotherapy that helps the immune system attack cancer cells. This combination may offer a novel approach to treating advanced cancers by potentially enhancing the immune response against tumors. ^{1 2 4 5 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. [2021]

3. England 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. [2023]

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

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

5. England 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. [2018]

6. England pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Could knee inflammatory synovitis be induced by pembrolizumab? [2018]

8. England pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. [2021]

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

Pembrolizumab in the management of metastatic melanoma. [2020]

10. England pubmed.ncbi.nlm.nih.gov

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

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

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. [2022]