Pembrolizumab + Bevacizumab for Brain Cancer and Lung Cancer

Recruiting at 1 trial location

Overseen By Tara McPartland

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Corticosteroids, Warfarin

Disqualifiers: Symptomatic brain metastases, Active autoimmune, Pneumonitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 84 months

42 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this phase 2 trial is to study the activity of pembrolizumab in combination with bevacizumab in patients with untreated brain metastases from melanoma or NSCLC to determine activity and safety of the drug combination. Furthermore, in patients who undergo resection of biopsy of a brain metastasis, we will evaluate biomarkers predictive of treatment benefit, and will also conduct correlative biomarker studies on extra-cerebral specimens in all patients in whom a systemic biopsy is feasible or in archival tumor tissue when available. A total of 53 eligible patients will be enrolled on this trial (40 with melanoma and 13 with NSCLC). Individual cohorts of the study can be stopped if insufficient activity is observed in the first stage of that cohort. The study will accrue for approximately 84 months, and will be open for approximately 12 additional months as patients on study are being followed.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had other systemic therapy within 14 days before starting the trial drugs, and you cannot use corticosteroids to control brain symptoms, except for low-dose use (10 mg of prednisone or equivalent).

What data supports the effectiveness of the drug Pembrolizumab plus Bevacizumab for brain cancer and lung cancer?

Research shows that combining bevacizumab with pembrolizumab can improve immune function and short-term survival in advanced lung cancer without specific genetic mutations. Additionally, bevacizumab has been effective in improving outcomes for lung cancer patients with brain metastases when combined with other treatments. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Bevacizumab safe for humans?

Research shows that Pembrolizumab, used alone or with other treatments, has been studied for safety in conditions like lung cancer and melanoma. While specific safety data for the combination with Bevacizumab is limited, Pembrolizumab has been generally well-tolerated in trials, but it can have side effects like fatigue and skin reactions. ^{3 6 7 8 9}

How is the drug combination of Pembrolizumab and Bevacizumab unique for treating brain and lung cancer?

The combination of Pembrolizumab and Bevacizumab is unique because it targets the immune system and blood vessels in tumors, potentially enhancing the immune response against cancer cells and reducing blood supply to tumors, which is different from traditional chemotherapy that directly kills cancer cells. ^{3 4 7 8 10}

Research Team

Harriett Kluger, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults with melanoma or non-squamous NSCLC who have small, untreated brain metastases not requiring immediate therapy. Participants must be in good general health with a life expectancy of at least 3 months and no severe autoimmune diseases, uncontrolled hypertension, significant bleeding disorders, or active infections like HIV/HBV/HCV. Pregnant/breastfeeding individuals and those treated with certain cancer drugs recently are excluded.

Inclusion Criteria

My NSCLC tumor shows PD-L1 presence based on a specific test.

You are expected to live for at least 3 more months.

Understanding and willingness to consent

Exclusion Criteria

My high blood pressure is not well controlled, even with medication.

I do not have any other active cancers besides the one being studied, except for skin cancer.

I haven't had chemotherapy or targeted therapy in the last 2 weeks and have recovered from previous treatment side effects.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with bevacizumab to study activity and safety in patients with untreated brain metastases from melanoma or NSCLC

84 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Pembrolizumab plus Bevacizumab

Trial Overview The study tests the combination of pembrolizumab plus bevacizumab on brain metastases from melanoma or NSCLC to assess effectiveness and safety. It includes biomarker studies to predict treatment benefits. The phase 2 trial will enroll 53 patients over approximately 84 months, with follow-up for an additional year.

Participant Groups

Group I: pembrolizumab plus bevacizumab Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The ARTEMIS study shows that combining the VEGF inhibitor bevacizumab with the EGFR inhibitor erlotinib significantly improves progression-free survival in patients with EGFR mutant non-small-cell lung cancer by over 6 months.

Patients with brain metastases and the EGFR L858R mutation experienced even greater benefits, highlighting the importance of personalized treatment strategies in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ARTEMIS highlights VEGF inhibitors as effective partners for EGFR TKIs in EGFR mutant NSCLC. Le, X., Nilsson, MB., Robichaux, JP., et al.[2021]

In a study of 85 patients with driver gene-negative stage IV lung adenocarcinoma, combining bevacizumab with pembrolizumab significantly improved the overall effective rate (48.89% vs. 27.50%) and disease control rate (93.33% vs. 72.50%) compared to the control group receiving only chemotherapy and pembrolizumab.

The combination treatment also led to a significant increase in cellular immune function and improved quality of life, with a median progression-free survival (PFS) of 13.00 months for the combination group compared to 9.00 months for the control group, indicating enhanced short-term therapeutic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Study on the Efficacy of Bevacizumab in Combination with Pembrolizumab on Cellular Immune Function in the Treatment of Driver Gene-Negative Stage IV Lung Adenocarcinoma. Gong, J., Gu, J., Jiang, L., et al.[2022]

In a study of 102 patients with advanced non-squamous non-small cell lung cancer, both pembrolizumab and bevacizumab combined with pemetrexed-platinum chemotherapy showed comparable efficacy in terms of progression-free survival (PFS) and overall survival (OS).

Patients with a baseline neutrophil-to-lymphocyte ratio (NLR) of 3.10 or lower experienced significantly better overall survival when treated with bevacizumab, suggesting that this biomarker could help tailor treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct Comparison Between the Addition of Pembrolizumab or Bevacizumab for Chemotherapy-Based First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer Lacking Driver Mutations. Liao, J., Liu, C., Long, Q., et al.[2022]

In a study comparing pembrolizumab combined with chemotherapy to atezolizumab combined with chemotherapy (with or without bevacizumab) in patients with advanced non-squamous NSCLC, pembrolizumab showed significantly better overall survival (OS) and progression-free survival (PFS).

The analysis indicated that pembrolizumab + chemotherapy had a hazard ratio of 0.80 for OS and 0.79 for PFS compared to atezolizumab + chemotherapy, suggesting it may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/-bevacizumab for the first-line treatment of non-squamous NSCLC: A matching-adjusted indirect comparison. Halmos, B., Burke, T., Kalyvas, C., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

In a phase 2 trial involving 36 patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC), pembrolizumab demonstrated activity, achieving a brain metastasis response in 22% of melanoma patients and 33% of NSCLC patients, with responses being durable for most.

The treatment had an acceptable safety profile, with serious adverse events occurring in a small percentage of patients, indicating that systemic immunotherapy could be a viable option for those with untreated or progressive brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Goldberg, SB., Gettinger, SN., Mahajan, A., et al.[2022]

In a phase 2 trial involving 42 patients with untreated brain metastases from non-small-cell lung cancer (NSCLC), pembrolizumab showed a 29.7% response rate in patients with PD-L1 expression of at least 1%, indicating its efficacy in treating brain metastases.

The treatment was generally safe, with serious adverse events occurring in 14% of patients, but no treatment-related deaths were reported, suggesting that pembrolizumab can be a viable option for selected patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. Goldberg, SB., Schalper, KA., Gettinger, SN., et al.[2021]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

In a real-world study of 54 patients with advanced non-squamous non-small cell lung cancer, the combination of carboplatin, pemetrexed, and pembrolizumab showed a higher disease control rate (86.7%) compared to carboplatin and pemetrexed alone (54%).

Patients with brain metastases treated with the combination therapy had a significantly lower progression rate (33.3%) compared to those receiving only carboplatin and pemetrexed (91.7%), indicating that this regimen may be particularly effective for this challenging patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. Afzal, MZ., Dragnev, K., Shirai, K.[2023]

References

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

ARTEMIS highlights VEGF inhibitors as effective partners for EGFR TKIs in EGFR mutant NSCLC. [2021]

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

Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, -189, and -407. [2021]

3. Egypt pubmed.ncbi.nlm.nih.gov

Clinical Study on the Efficacy of Bevacizumab in Combination with Pembrolizumab on Cellular Immune Function in the Treatment of Driver Gene-Negative Stage IV Lung Adenocarcinoma. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Direct Comparison Between the Addition of Pembrolizumab or Bevacizumab for Chemotherapy-Based First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer Lacking Driver Mutations. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/-bevacizumab for the first-line treatment of non-squamous NSCLC: A matching-adjusted indirect comparison. [2021]

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

Pembrolizumab. [2022]

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

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]

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

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. [2021]

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

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2023]

10. China pubmed.ncbi.nlm.nih.gov

A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. [2023]