V940 + Pembrolizumab for Non-Small Cell Lung Cancer

Recruiting at 248 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Pembrolizumab

Must not be taking: PD-1 inhibitors

Disqualifiers: SCLC, ALK rearrangements, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

680 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining intismeran autogene (V940) with pembrolizumab after surgery helps individuals with non-small cell lung cancer (NSCLC) remain cancer-free longer than using a placebo with pembrolizumab. Researchers focus on patients whose tumors did not fully respond to treatment before surgery. Suitable candidates include those with resectable Stage II, IIIA, or IIIB (N2) NSCLC who have not achieved a complete tumor response after pre-surgery treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received certain cancer treatments or vaccines recently. It's best to discuss your current medications with the trial team.

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

Research shows that pembrolizumab is generally well-tolerated by patients. It has been used in many studies and already has FDA approval for treating various cancers. Most people experience manageable side effects like tiredness, nausea, or a skin rash. Serious side effects are less common but can include lung or liver inflammation.

For intismeran autogene (also known as V940), less information is available because it is still under study. However, early research has not revealed major safety concerns. Common side effects might include reactions at the injection site, such as pain or swelling. As this treatment is in a later stage of testing, researchers express some confidence in its safety.

Overall, while pembrolizumab has a well-documented safety record, intismeran autogene remains under investigation. Both treatments are considered relatively safe based on current data, but participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they combine pembrolizumab, a well-known immunotherapy, with innovative approaches. In one arm, pembrolizumab is paired with intismeran autogene, a new personalized vaccine designed to train the immune system to target cancer cells more effectively. This combination could enhance the body's natural defenses against cancer in a way that current standard treatments, which typically involve chemotherapy and radiation, do not. By integrating these methods, there's potential to improve outcomes and provide a more targeted treatment option for patients.

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

Research has shown that pembrolizumab, also known as KEYTRUDA, effectively treats various cancers, including non-small cell lung cancer (NSCLC). It aids the immune system in identifying and combating cancer cells. Studies have found that pembrolizumab can extend life and slow cancer growth. In this trial, one group of participants will receive pembrolizumab with a placebo, while another group will receive pembrolizumab combined with intismeran autogene (also called V940). This combination is being tested to determine if it can better prevent cancer recurrence after surgery. Early results suggest this combination might help patients remain cancer-free longer. However, further research is needed to confirm these findings. ^{1 2 3 5 6}

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 resectable Stage II-III non-small cell lung cancer (NSCLC) who haven't had prior treatments and whose tumors didn't fully respond to initial therapy before surgery. They must be in good physical condition, not need EGFR-targeted primary therapy, and can have controlled hepatitis B or C or HIV.

Inclusion Criteria

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

My cancer does not have EGFR mutations, so I don't need EGFR-targeted therapy.

I have HIV and it is well controlled with medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab and chemotherapy for up to 4 cycles before surgery

12 weeks

4 visits (in-person)

Surgical Resection

Participants undergo surgical resection of the tumor

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive pembrolizumab and V940 or placebo for up to 7 cycles post-surgery

42 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

97 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• V940

Trial Overview The study tests if V940 combined with pembrolizumab extends the time patients remain cancer-free post-surgery compared to a placebo plus pembrolizumab. It's for NSCLC patients whose cancer persisted after neoadjuvant treatment and surgery.

How Is the Trial Designed?

Group I: Pembrolizumab + Intismeran autogene Experimental Treatment 7 Interventions

For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m\^2 or carboplatin area under the curve \[AUC\] 5 or 6 mg/mL/min, pemetrexed 500 mg/m\^2, gemcitabine 1000 mg/m\^2, paclitaxel 175 mg/m\^2 or 200 mg/m\^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to \~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to \~42 weeks).

Group II: Pembrolizumab + Placebo Active Control 7 Interventions

For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m\^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m\^2, gemcitabine 1000 mg/m\^2, paclitaxel 175 mg/m\^2 or 200 mg/m\^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to \~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to \~42 weeks).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

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]

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, 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]

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]

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 (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]

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]

Citations

1. 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 ...

2. 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 ...

3. 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 ...

4. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_15384.a-study-of-intismeran-autogene-v940-plus-pembrolizumab-mk-3475-versus-placebo-plus-pembrolizumab-in-participants-with-non-small-cell-lung-cancer-v940.html

Clinical Trial Details The goal of this study is to evaluate intismeran autogene plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09110

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

6. merckclinicaltrials.com merckclinicaltrials.com/trial/nct06623422/

Study: Pembrolizumab With or Without V940 in Lung Cancer 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 ...