Volrustomig + Chemotherapy for Advanced Non-Small Cell Lung Cancer

(eVOLVE-Lung02 Trial)

Recruiting at 273 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids

Disqualifiers: Small-cell lung cancer, Spinal cord compression, Symptomatic 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression

1200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatment combinations for advanced non-small cell lung cancer (NSCLC). It evaluates the effectiveness of volrustomig (an experimental treatment) with chemotherapy against pembrolizumab (also known as KEYTRUDA, an immunotherapy drug) with chemotherapy for patients whose cancer cannot be surgically removed. Participants should have advanced NSCLC without specific genetic mutations and no symptoms from brain metastases (cancer spread to the brain). This trial offers those seeking new treatment options for their lung cancer an opportunity to participate. As a Phase 3 trial, it represents the final step before FDA approval, providing participants access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that volrustomig, a type of immunotherapy, has been tested in people with advanced cancers. These studies found that while volrustomig can work well, it sometimes causes side effects that lead patients to stop treatment. However, many patients find it manageable overall.

Pembrolizumab, the other treatment under study, has already received FDA approval for several conditions, including some lung cancers. Previous studies have shown that most patients tolerate pembrolizumab well, though some may experience side effects like tiredness and nausea.

Both treatments have been used with chemotherapy, which can also cause side effects. Discussing expectations and side effect management with the study team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Volrustomig because it offers a novel approach to treating advanced non-small cell lung cancer. Unlike standard treatments that rely heavily on chemotherapy and immune checkpoint inhibitors like pembrolizumab, Volrustomig is a bispecific antibody designed to simultaneously engage the immune system more effectively. This dual-targeting mechanism could potentially enhance the body's ability to recognize and attack cancer cells, offering hope for better outcomes in patients with this challenging condition.

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

Research shows that volrustomig, one of the treatments in this trial, has promising results for treating advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy. Earlier studies demonstrated that volrustomig effectively blocked certain proteins (PD-1 and CTLA-4), which help activate the immune system to fight cancer cells. This combination has shown encouraging results, particularly in patients with advanced NSCLC. Some studies even suggest that volrustomig with chemotherapy might nearly double the response time compared to pembrolizumab with chemotherapy. Pembrolizumab, the other treatment option in this trial, is already known for its effectiveness in treating NSCLC, making it a strong comparison in this trial. Both treatments are being tested to determine which works better for patients with a specific type of lung cancer that has lower levels of a protein called PD-L1. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with stage IV non-small cell lung cancer (NSCLC) without certain genetic mutations or rearrangements. Candidates should not have a history of other cancers within the last 2 years, except some skin cancers and localized cancers that were treated. They must not have brain metastases requiring steroids or mixed NSCLC histology.

Inclusion Criteria

My cancer does not have EGFR, ALK, or ROS1 mutations.

My cancer does not have genetic changes treatable by approved drugs.

My lung cancer type was confirmed by lab tests.

Exclusion Criteria

My lung cancer is a mix of small-cell and non-small cell types.

I have spinal cord compression.

I had cancer before, but it was treated over 2 years ago and is not likely to come back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either volrustomig plus chemotherapy or pembrolizumab plus chemotherapy via IV infusion

Until disease progression

Regular visits for IV infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 6 years

Periodic visits for survival follow-up

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Volrustomig

Trial Overview The study compares two treatments: Volrustomig combined with chemotherapy versus Pembrolizumab (also known as Keytruda) with chemotherapy in patients whose tumors express PD-L1 <50%. The goal is to see which treatment works better for this specific group of lung cancer patients.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 4 Interventions

Volrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion

Group II: Arm 2 Active Control 4 Interventions

Pembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion

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?

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

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 JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

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 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]

Adjuvant platinum-based chemotherapy is the standard treatment for patients with resected non-small-cell lung cancer (NSCLC) stage IB to IIIA, but many still face disease recurrence, highlighting the need for more effective therapies.

The ALCHEMIST trial is investigating the efficacy of pembrolizumab, a PD-1 inhibitor, in combination with chemotherapy to potentially improve outcomes compared to standard chemotherapy alone, with the aim of reducing recurrence rates in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). Sands, JM., Mandrekar, SJ., Kozono, D., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., 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) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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 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]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

In the KEYNOTE-189 study, patients with non-squamous non-small cell lung cancer who received the combination of pembrolizumab, pemetrexed, and platinum had a median progression-free survival (PFS) of 9.3 months, significantly longer than the 6.6 months observed in the placebo group, indicating enhanced efficacy of the treatment.

The objective response rate was also higher in the pembrolizumab group (58.7%) compared to the placebo group (28.9%), while the incidence of severe treatment-emergent adverse events (grade ≥3) was similar across both treatment arms, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed maintenance with or without pembrolizumab in non-squamous non-small cell lung cancer: A cross-trial comparison of KEYNOTE-189 versus PARAMOUNT, PRONOUNCE, and JVBL. Garon, EB., Kim, JS., Govindan, R.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11262897/

Bispecific immunotherapy MEDI5752 or volrustomig and ... A phase I, open-label study (MedImmune LLC, NCT03530397) of MEDI5752 monotherapy 2.25–2,500 mg intravenous every 3 weeks showed encouraging antitumor activity ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424009365

OA11.04 Volrustomig + platinum doublet chemotherapy ... Volrustomig 750mg + CTx demonstrates robust PD-1/CTLA-4 blockade, manageable safety, and promising efficacy in 1L advanced NSCLC, especially in patients with ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS8652

eVOLVE-Lung02: A phase 3 study of first-line (1L) ... Outcomes to first-line pembrolizumab in patients with non-small cell lung cancer and a PD-L1 tumor proportion score ≥90%.

4. onclive.com onclive.com/view/high-dose-medi5752-induces-clinical-benefit-in-nsclc-at-the-cost-of-significant-toxicity

High-Dose MEDI5752 Induces Clinical Benefit in NSCLC ... “The 1500-mg MEDI5752 plus chemotherapy showed improved antitumor activity—almost double the duration of response compared [with] pembrolizumab ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05984277

NCT05984277 | A Global Study of Volrustomig (MEDI5752) ... A Global Study of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for Participants With Metastatic Non-small Cell Lung Cancer.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39390972/

The efficacy and safety of a novel PD-1/CTLA-4 bispecific ... In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab-based regimens showed moderate antitumor efficacy with a generally tolerable and ...

7. ejgo.org ejgo.org/pdf/10.3802/jgo.2024.35.e82

Bispecific immunotherapy MEDI5752 or volrustomig and ... MEDI5752 is a monovalent bispecific immunotherapy and is strategically unique as it combines both anti programmed cell death 1 and anti ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.107

Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 ... MEDI5752 monotherapy showed deep and durable antitumor activity in pts with advanced RCC, despite high rates of treatment D/C, particularly in the 1L setting.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04172454

Safety and Efficacy of AK104, a PD-1/CTLA-4 Bispecific ... A multicenter, open-label, phase 1b/2 study to evaluate the safety and efficacy of AK104, a PD-1 and CTLA-4 bispecific antibody, in selected advanced solid ...