V940 + Pembrolizumab for Kidney Cancer

(INTerpath-004 Trial)

Recruiting at 65 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Pembrolizumab

Must not be taking: Steroids, Cancer vaccines

Disqualifiers: Immunodeficiency, Active malignancy, 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: 9

Duration: 54 weeks

272 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic anticancer therapy, steroids, or have received a live vaccine recently, you may need to stop those before joining the trial.

What data supports the effectiveness of the drug Pembrolizumab for kidney cancer?

Research shows that pembrolizumab, when used as an adjuvant therapy (additional treatment given after the primary treatment), significantly improves disease-free survival in patients with renal cell carcinoma after surgery. Additionally, a combination of axitinib and pembrolizumab has shown a 73% response rate in advanced renal cell carcinoma. ^{1 2 3 4 5}

Is the combination of V940 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, and nausea. Some serious side effects include pneumonitis (lung inflammation), colitis (colon inflammation), and thyroid disorders. There have also been rare cases of kidney issues, so it's important to discuss potential risks with your doctor. ^{1 4 6 7 8}

How does the drug V940 + Pembrolizumab differ from other kidney cancer treatments?

Pembrolizumab is a unique drug because it is an immune checkpoint inhibitor that helps the body's immune system attack cancer cells by blocking the PD-1 pathway, which is different from traditional chemotherapy that directly kills cancer cells. This combination with V940 may offer a novel approach for kidney cancer by potentially enhancing the immune response against the tumor. ^{1 3 4 8 9}

What is the purpose of this trial?

The primary objective of the study is to compare intismeran autogene plus pembrolizumab to placebo plus pembrolizumab in participants with renal cell carcinoma (RCC) with respect to disease-free survival (DFS) as assessed by the investigator. The primary hypothesis is that intismeran autogene plus pembrolizumab is superior to placebo plus pembrolizumab with respect to DFS.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with a specific kidney cancer (clear cell or papillary renal cell carcinoma). They should be at intermediate-high risk, have had surgery to remove the tumor and any isolated metastases within the last 12 weeks, and be in good physical condition (ECOG status of 0 or 1).

Inclusion Criteria

My kidney cancer is confirmed to be either clear cell or papillary type.

My kidney cancer is at an intermediate to high risk level or I have no signs of disease after metastasis.

I had surgery to remove my primary cancer and any solid metastatic tumors.

Exclusion Criteria

I haven't had cancer treatment or experimental drugs in the last 4 weeks.

I haven't had radiotherapy or needed steroids for side effects in the last 2 weeks.

I have not received a live vaccine in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive V940 or placebo plus Pembrolizumab for up to 54 weeks

54 weeks

9 visits (in-person) every 6 weeks

Follow-up

Participants are monitored for disease-free survival and overall survival

43 months

Long-term follow-up

Participants are monitored for overall survival and distant metastasis-free survival

96 months

Treatment Details

Interventions

• Pembrolizumab
• V940

Trial Overview The study aims to see if adding V940 to pembrolizumab improves disease-free survival compared to using pembrolizumab with a placebo. Participants will randomly receive either the combination of V940 and pembrolizumab or a placebo plus pembrolizumab.

Participant Groups

Group I: Intismeran autogene + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks (Q3W) for up to 9 doses plus Pembrolizumab 400 mg via an intravenous (IV) infusion every 6 weeks (Q6W) for 9 cycles (up to \~54 weeks). Each cycle is 6 weeks.

Group II: Placebo + Pembrolizumab Active Control 2 Interventions

Participants will receive placebo as an IM injection Q3W for up to 9 doses plus Pembrolizumab 400 mg via an IV infusion Q6W for 9 cycles (up to \~54 weeks). Each cycle is 6 weeks.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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

ModernaTX, Inc.

Industry Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

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]

Adjuvant pembrolizumab significantly improves disease-free survival in patients with high-risk renal cell carcinoma (RCC) after surgery, as shown in the KEYNOTE 564 trial.

Pembrolizumab is an effective and well-tolerated treatment option for patients with surgically resected RCC, paving the way for future research on patient selection and biomarkers for therapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. Serzan, M., Atkins, MB.[2022]

This study presents the first known case of a patient with metastatic melanoma who was successfully treated with pembrolizumab while undergoing hemodialysis, highlighting its potential efficacy in patients with end-stage renal disease.

Pembrolizumab, an FDA-approved monoclonal antibody for metastatic melanoma and non-small cell lung cancer, shows promise for use in patients with renal complications, although specific dosing guidelines for such patients are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. Chang, R., Shirai, K.[2019]

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]

The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating strong efficacy for this treatment regimen.

This finding suggests that the dual approach of targeting both tumor growth and immune response may be effective in managing advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor for non-small cell lung carcinoma, has been linked to adverse renal outcomes, including acute kidney injury.

In a reported case, a patient developed acute tubulointerstitial nephritis after starting pembrolizumab, and while renal function improved with long-term corticosteroid treatment after discontinuation of the drug, it only improved partially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. Basnet, S., Dhital, R., Tharu, B.[2020]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

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

Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

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

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

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. [2020]

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]