Rilvegostomig + Pembrolizumab + Chemotherapy for Lung Cancer

Recruiting at 233 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, others

Disqualifiers: Small cell, Brain metastases, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 5 years

880 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of ARTEMIDE-Lung02 is to assess the efficacy and safety of rilvegostomig in combination with platinum-based chemotherapy for the first-line (1L) treatment of patients with metastatic squamous non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on steroids or anticonvulsants for brain metastases, you must not have used them for at least 4 weeks before starting the study.

What evidence supports the effectiveness of the drug combination Rilvegostomig, Pembrolizumab, and Chemotherapy for lung cancer?

Research shows that nab-paclitaxel (a form of paclitaxel) combined with carboplatin is effective as a first-line treatment for advanced non-small-cell lung cancer (NSCLC), improving response rates compared to traditional paclitaxel. This combination is well-tolerated and offers benefits in certain patient groups, such as those with squamous cell histology and elderly patients. ^{1 2 3 4 5}

Is the combination of Rilvegostomig, Pembrolizumab, and Chemotherapy safe for humans?

The combination of albumin-bound paclitaxel (nab-paclitaxel) and carboplatin has been studied for safety in lung cancer, showing a different toxicity profile with a lower rate of severe neutropenia (low white blood cell count) compared to solvent-based paclitaxel. Safety data for Rilvegostomig specifically is not provided, but the combination of these drugs has been evaluated in various studies for lung cancer. ^{1 2 4 6 7}

What makes the drug combination of Rilvegostomig, Pembrolizumab, and Chemotherapy unique for lung cancer treatment?

This treatment is unique because it combines Rilvegostomig, a novel drug, with Pembrolizumab (an immune therapy that helps the body fight cancer) and chemotherapy, potentially enhancing the immune response and improving outcomes for lung cancer patients compared to standard chemotherapy alone. ^{2 8 9 10 11}

Eligibility Criteria

This trial is for patients with metastatic squamous non-small cell lung cancer (mNSCLC) that expresses PD-L1. It's their first treatment attempt for this condition.

Inclusion Criteria

I have a tumor that can be measured and has not been treated with radiation.

My organs and bone marrow are working well.

My lung cancer is confirmed to be squamous non-small cell type.

Exclusion Criteria

I do not have an active immune system disorder or ongoing infections.

My cancer has small cell and neuroendocrine features.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rilvegostomig or pembrolizumab in combination with platinum-based chemotherapy

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Treatment Details

Interventions

• Carboplatin
• Nab-paclitaxel
• Paclitaxel
• Pembrolizumab
• Rilvegostomig

Trial Overview The study tests the effectiveness and safety of a new drug, Rilvegostomig, combined with platinum-based chemotherapy versus Pembrolizumab plus the same chemotherapy in treating mNSCLC.

Participant Groups

Group I: Arm A Experimental Treatment 4 Interventions

Rilvegostomig in combination with carboplatin and paclitaxel or nab-paclitaxel followed by rilvegostomig

Group II: Arm B Active Control 4 Interventions

Pembrolizumab in combination with carboplatin and paclitaxel or nab-paclitaxel followed by pembrolizumab

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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 III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

Nab-paclitaxel (Abraxane) combined with carboplatin significantly improved the objective response rate in patients with advanced non-small cell lung cancer (NSCLC) compared to solvent-bound paclitaxel, although it did not extend progression-free or overall survival.

The nab-paclitaxel regimen showed a manageable safety profile with fewer instances of severe neutropenia, peripheral neuropathy, and muscle pain compared to solvent-bound paclitaxel, making it a valuable first-line treatment option for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-Bound Paclitaxel: A Review in Non-Small Cell Lung Cancer. Blair, HA., Deeks, ED.[2018]

Nab-paclitaxel significantly improves overall response (OR) and partial response (PR) rates in advanced non-small cell lung cancer (NSCLC), especially in squamous cell carcinoma and as a second-line treatment, based on a meta-analysis of 35 studies involving various trial designs.

While nab-paclitaxel shows marginal improvements in overall survival (OS) and progression-free survival (PFS), the evidence regarding its safety profile and reduction of adverse events remains inconclusive, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies. Suwannasom, N., Sriaksorn, N., Thepmalee, C., et al.[2023]

In a Phase 2 study involving 29 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 inhibitor treatment, nab-paclitaxel demonstrated a promising objective response rate (ORR) of 55.2%, indicating its efficacy as a subsequent treatment option.

The treatment was associated with manageable safety profiles, with significant toxicities including leukopenia (27.6%) and neutropenia (31.0%), suggesting that while nab-paclitaxel is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Sonoda, T., Umeda, Y., Demura, Y., et al.[2023]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

This study is the first to evaluate the combination of necitumumab with pembrolizumab and platinum-based chemotherapy in patients with untreated squamous cell lung cancer (SqCLC), aiming to enhance tumor immunity and therapeutic effects.

The trial will assess safety and efficacy, with 42 patients enrolled in phase II to determine the overall response rate and other important outcomes like progression-free survival and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer Study: (NEJ048A/NEXUS). Miyanaga, A., Asahina, H., Watanabe, S., et al.[2023]

In a trial involving 50 patients with advanced nonsquamous non-small cell lung cancer (NSCLC), the combination of nab-paclitaxel, carboplatin, and bevacizumab showed a response rate of 31% and a median progression-free survival of 9.8 months, indicating promising efficacy as a first-line treatment.

The treatment was generally well tolerated, with manageable adverse effects, primarily neutropenia (54%) and fatigue (17%), suggesting that this combination therapy could be a viable option for patients despite the risk of moderate toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of nanoparticle albumin-bound paclitaxel, carboplatin, and bevacizumab in first-line patients with advanced nonsquamous non-small cell lung cancer. Reynolds, C., Barrera, D., Jotte, R., et al.[2022]

References

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

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

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

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. [2022]

4. Thailand pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Albumin-Bound Paclitaxel: A Review in Non-Small Cell Lung Cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies. [2023]

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

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. [2023]

8. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

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

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. [2020]

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

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer Study: (NEJ048A/NEXUS). [2023]

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

Phase II trial of nanoparticle albumin-bound paclitaxel, carboplatin, and bevacizumab in first-line patients with advanced nonsquamous non-small cell lung cancer. [2022]