V940 + Pembrolizumab for Lung Cancer

(INTerpath-002 Trial)

Recruiting at 267 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Platinum chemotherapy

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Small cell lung cancer, Immunodeficiency, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Up to approximately 1 year

868 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with certain stages of non-small cell lung cancer (NSCLC) that surgery has completely removed. It compares the effects of adding intismeran autogene (also known as V940, an experimental treatment) to pembrolizumab, a common cancer medication, against using a placebo with pembrolizumab to determine which is more effective at preventing cancer recurrence. Suitable candidates for this trial have had their NSCLC fully removed, received initial chemotherapy, and currently show no signs of cancer. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

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 chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop or adjust it before starting the study medication.

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

Research shows that pembrolizumab, already approved by the FDA for other cancers, is generally well-tolerated. Studies have found common side effects include fatigue, rash, and itching, which are usually mild and manageable.

Intismeran autogene (also called V940) is still under testing, so less is known about its safety. Early research suggests it might cause mild to moderate side effects similar to other vaccines, such as injection site pain or a brief fever.

Since this trial is in the later stages (Phase 3), earlier studies have indicated the treatment is fairly safe. However, as with any clinical trial, unexpected side effects may occur. Researchers closely monitor participants to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about intismeran autogene combined with pembrolizumab for lung cancer because it offers a novel approach to treatment. Unlike standard therapies like chemotherapy, which target rapidly dividing cells, intismeran autogene uses a personalized immunotherapy approach. It works by training the immune system to recognize and attack cancer cells more effectively. This targeted mechanism could potentially lead to better outcomes and fewer side effects compared to traditional treatments. Additionally, the combination with pembrolizumab, an established immune checkpoint inhibitor, might enhance the immune response against the cancer.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

In this trial, participants will receive either V940, a type of mRNA therapy, with pembrolizumab, or a placebo with pembrolizumab. Research has shown that V940 combined with pembrolizumab yields promising results for treating certain cancers. Specifically, earlier studies demonstrated that this combination lowered the risk of cancer recurrence or death by 49%. It also reduced the likelihood of cancer spreading or causing death by 62%. These findings suggest that this treatment could significantly extend the time patients remain disease-free. Evidence indicates that V940, when used with pembrolizumab, may effectively target and destroy cancer cells, helping to prevent the disease from returning. ^{1 3 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with Stage II, IIIA, or IIIB non-small cell lung cancer that's been surgically removed. They must have completed at least one round of standard chemo and can't have any remaining signs of cancer. People with well-controlled HIV on ART, or past hepatitis B/C with undetectable viral loads can join. Exclusions include recent investigational drug use, chronic high-dose steroids, autoimmune disease treatments within 2 years, prior PD-1/PD-L1 therapy, active infections needing systemic treatment.

Inclusion Criteria

It's been less than 6 months since my surgery aimed at curing my cancer and starting pembrolizumab.

I had hepatitis C but my viral load is now undetectable.

I have received at least one round of standard chemotherapy for my cancer.

Exclusion Criteria

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

I have had initial treatment before surgery for my lung cancer.

I am receiving or can receive radiotherapy for my lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive V940 or placebo plus pembrolizumab for adjuvant treatment of resected NSCLC

Up to approximately 1 year

9 visits (in-person) every 3 weeks for V940/placebo, 9 visits (in-person) every 6 weeks for pembrolizumab

Follow-up

Participants are monitored for disease-free survival and other outcomes

Up to ~78 months

Long-term follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to ~12 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Placebo
• V940

Trial Overview The study tests if adding V940 to pembrolizumab (a known immunotherapy) improves disease-free survival compared to a placebo plus pembrolizumab in patients who've had surgery for NSCLC. Participants are randomly assigned to either the V940 combo or the placebo combo after their surgery and initial chemotherapy.

How Is the Trial Designed?

Group I: Intismeran autogene + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection once every 3 weeks for 9 doses PLUS 400 mg of pembrolizumab via intravenous (IV) infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.

Group II: Placebo + Pembrolizumab Active Control 2 Interventions

Participants will receive intismeran autogene-matched placebo via IM injection once every 3 weeks for 9 doses PLUS 400 mg of pembrolizumab via IV infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.

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

Published Research Related to This Trial

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 involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

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, 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]

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) 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]

Citations

1. merck.com merck.com/news/merck-and-moderna-initiate-phase-3-trial-evaluating-adjuvant-v940-mrna-4157-in-combination-with-keytruda-pembrolizumab-after-neoadjuvant-keytruda-and-chemotherapy-in-patients-with-certain-ty/

Merck and Moderna Initiate Phase 3 Trial Evaluating ... Merck and Moderna have initiated Phase 3 randomized clinical trials evaluating mRNA-4157 (V940) in combination with KEYTRUDA as an adjuvant ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38246194/

Individualised neoantigen therapy mRNA-4157 (V940) plus ... Our study aimed to evaluate whether mRNA-4157 (V940), a novel mRNA-based individualised neoantigen therapy, combined with pembrolizumab, improved recurrence- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06077760

NCT06077760 | A Study of Intismeran Autogene (V940) ... The goal of this study is to evaluate intismeran autogene plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of margin negative ...

4. merck.com merck.com/news/moderna-merck-announce-3-year-data-for-mrna-4157-v940-in-combination-with-keytruda-pembrolizumab-demonstrated-sustained-improvement-in-recurrence-free-survival-distant-metastasis-free-su/

Moderna & Merck Announce 3-Year Data For mRNA-4157 ... mRNA-4157 (V940) in combination with KEYTRUDA reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death by 62% compared to ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS8116

The phase 3 INTerpath-002 study design Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06623422

NCT06623422 | A Study of Pembrolizumab (MK-3475 ... The goal of this study is to learn if people who receive intismeran autogene and pembrolizumab after surgery are cancer-free longer than people who receive ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12467296/

mRNA Vaccines in Modern Immunotherapy for Non-Small ... NCT06077760 is a large phase III trial (n = 868) comparing intismeran autogene (V940) + pembrolizumab with placebo + pembrolizumab in patients ...

8. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06077760/

A Study of V940 Plus Pembrolizumab Versus Placebo Plus ... The goal of this study is to evaluate intismeran autogene plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of margin negative ...