Rilvegostomig or Pembrolizumab for Non-Small Cell Lung Cancer

(ARTEMIDELung04 Trial)

Recruiting at 127 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

Trial Summary

What is the purpose of this trial?

The purpose of ARTEMIDE-Lung04 is to assess the efficacy and safety of rilvegostomig compared with pembrolizumab monotherapy as 1L treatment in participants with mNSCLC and whose tumors express PD-L1.

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.

What data supports the effectiveness of the drug pembrolizumab for non-small cell lung cancer?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, is effective in treating advanced non-small cell lung cancer, especially in patients whose tumors have a high level of a protein called PD-L1. Studies have demonstrated that pembrolizumab can improve survival compared to traditional chemotherapy. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab is generally well tolerated, with common side effects including itching, tiredness, and loss of appetite. Serious heart-related side effects are rare, occurring in about 1% of cases. ^{6 7 8 9 10}

How is the drug Rilvegostomig or Pembrolizumab unique for treating non-small cell lung cancer?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, enhancing the body's immune response against cancer cells. It is particularly effective in patients with high PD-L1 expression, offering better survival outcomes compared to traditional chemotherapy. ^{1 2 3 4 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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]

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 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]

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]

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]

References

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

2. England 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. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]

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

Pembrolizumab in lung cancer: current evidence and future perspectives. [2020]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

6. United States 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. [2022]

7. United States 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. [2019]

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

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. [2023]

9. England 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. [2020]

10. United States 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. [2021]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]