Rilvegostomig or Pembrolizumab for Non-Small Cell Lung Cancer

(ARTEMIDELung04 Trial)

Recruiting at 216 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids, Anticonvulsants, Immunosuppressives, others

Disqualifiers: Organ transplant, Autoimmune disorders, others

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: Unknown

Duration: Up to approximately 5 years

830 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares the effectiveness and safety of two treatments for people with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a specific marker called PD-L1. The treatments are rilvegostomig, an experimental treatment, and pembrolizumab, an immunotherapy drug. The goal is to determine which treatment works better as the first-line therapy. Suitable candidates for this trial include individuals with mNSCLC who have not responded to other specific genetic-based treatments and experience symptoms like persistent cough or chest pain. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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, if you are on steroids or immunosuppressive treatments for autoimmune or inflammatory disorders, you may need to stop, as these are part of the exclusion criteria.

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

Previous studies have shown that rilvegostomig, a drug blocking certain proteins involved in cancer growth, is safe for people with advanced non-small cell lung cancer (NSCLC). Research indicates that most side effects are mild to moderate, though reports of more serious side effects exist but are less common.

Pembrolizumab, already FDA-approved for some cancers, has a well-known safety record. It is generally well-tolerated, though some people might experience side effects like tiredness, nausea, or skin reactions.

This trial compares both treatments, and previous data suggest they are safe for most patients. However, individual experiences may vary, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

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

Researchers are excited about Rilvegostomig for non-small cell lung cancer because it introduces a new mechanism of action by targeting a specific pathway not addressed by current treatments like chemotherapy and other immunotherapies. Unlike the standard options, Rilvegostomig may offer a more precise approach, potentially leading to better outcomes and fewer side effects. Pembrolizumab, on the other hand, is already a well-known immunotherapy that enhances the body's immune response against cancer cells. The combination of these two treatments could provide a more comprehensive strategy, offering hope for improved effectiveness in treating this type of lung cancer.

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

This trial will compare the effectiveness of rilvegostomig and pembrolizumab for treating non-small cell lung cancer. Studies have shown that rilvegostomig, which participants in this trial may receive, can help the immune system fight cancer by targeting the proteins PD-1 and TIGIT. Previous research has demonstrated lasting benefits for patients with PD-L1–positive metastatic non-small cell lung cancer (mNSCLC). Early results suggest positive outcomes when patients used rilvegostomig as their first treatment. Meanwhile, pembrolizumab, another treatment option in this trial, is a well-known therapy that effectively helps the immune system attack cancer in patients with PD-L1–positive tumors by targeting PD-1. Both treatments have shown promise in treating mNSCLC, offering patients potential options for effective care. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced non-small cell lung cancer that has high levels of a protein called PD-L1. Participants should not have had prior treatments for their metastatic cancer.

Inclusion Criteria

Minimum life expectancy of 12 weeks

My organs and bone marrow are working well.

My lung cancer has been confirmed by lab tests.

Exclusion Criteria

My brain metastases are stable, and I haven't needed steroids or seizure medicine for 4 weeks.

I do not have severe illnesses that would prevent me from following the study's requirements.

I have had an organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either rilvegostomig or pembrolizumab as first-line treatment for PD-L1-high metastatic non-small cell lung cancer

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Rilvegostomig

Trial Overview The study is testing the effectiveness and safety of two drugs: Rilvegostomig and Pembrolizumab. Each participant will receive one of these as a first-line treatment to compare which works better.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 1 Intervention

Drug: rilvegostomig

Group II: Arm B Active Control 1 Intervention

Drug: Pembrolizumab

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., et al.[2020]

In a study of 1010 patients with metastatic non-small-cell lung cancer (NSCLC) and high PD-L1 expression receiving first-line pembrolizumab, the occurrence of immune-related adverse events (irAEs) was significantly associated with better treatment outcomes, including higher objective response rates and improved progression-free and overall survival.

The analysis suggests that irAEs could serve as a surrogate marker for the efficacy of pembrolizumab, indicating that patients experiencing these adverse events may have a more favorable response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes. Cortellini, A., Friedlaender, A., Banna, GL., et al.[2021]

In a study of 271 advanced non-small-cell lung cancer patients treated with PD-1 antibodies, 42.8% experienced immune-related adverse events (irAEs), which were linked to lower overall survival (OS) rates, particularly in those with severe irAEs like colitis.

Patients who required treatment interruption due to irAEs had significantly lower OS compared to those who continued therapy, highlighting the need for better management strategies for irAEs to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis. Ksienski, D., Wai, ES., Croteau, N., et al.[2019]

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]

The PePS2 trial demonstrated that pembrolizumab can be safely administered to patients with non-small-cell lung cancer (NSCLC) and a performance status of 2, with a toxicity rate of 28% and no severe treatment-related adverse events, indicating a manageable safety profile.

Efficacy outcomes showed that 38% of first-line and 36% of subsequent-line patients experienced durable clinical benefit, with higher response rates correlating with tumor proportion scores, suggesting that pembrolizumab is effective for this underserved patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Middleton, G., Brock, K., Savage, J., et al.[2020]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

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, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

Citations

1. oncodaily.com oncodaily.com/oncolibrary/artemide-01-trial

ARTEMIDE-01 Trial Demonstrates Promising Efficacy and ... Rilvegostomig, a dual PD-1/TIGIT inhibitor, shows durable responses and favorable safety in PD-L1–positive metastatic NSCLC in the ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8521

First-line (1L) datopotamab deruxtecan (Dato-DXd) + ... Dato-DXd + rilvegostomig had encouraging activity as 1L treatment for pts with a/mNSCLC without AGAs, with responses seen in both histologies and across all PD ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D702BC00001

A Global Phase III Study of Rilvegostomig or ... This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03314-8/fulltext

1446P Preliminary efficacy and safety of rilvegostomig ... Rilvegostomig is a bispecific, humanised IgG1 targeting PD-1 and TIGIT, receptors that suppress antitumour T cell activity. Initial data from the first-in-human ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06868277

NCT06868277 | A Global Phase III Study of Rilvegostomig ... The purpose of ARTEMIDE-Lung04 is to assess the efficacy and safety of rilvegostomig compared with pembrolizumab monotherapy as 1L treatment in participants ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06692738

NCT06692738 | A Global Phase III Study of Rilvegostomig ... This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, ...