Volrustomig + Chemotherapy for Non-Small Cell Lung Cancer

(eVOLVE-01 Trial)

Recruiting at 75 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Steroids

Disqualifiers: Spinal cord compression, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Up to 2.4 years

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, volrustomig (an experimental treatment), combined with chemotherapy for non-small cell lung cancer (NSCLC). Researchers aim to assess the treatment's safety, effectiveness, and interaction with the body. The trial includes different groups, each receiving a unique combination of volrustomig, chemotherapy, and sometimes another drug, ramucirumab. Patients with NSCLC who have not received previous treatments for advanced stages and have no specific genetic mutations in their tumors might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering patients a chance to contribute to important advancements in NSCLC 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 had prior chemotherapy or systemic therapy for Stage IV NSCLC, which might imply some restrictions on current treatments.

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

Research has shown that volrustomig, a treatment under study for lung cancer, is generally well-tolerated. It blocks certain proteins that help cancer cells evade the immune system. In earlier studies, combining volrustomig with chemotherapy resulted in manageable side effects. This indicates that while some side effects occurred, they were not severe for most participants.

Specifically, one study found that when volrustomig was used with platinum-based chemotherapy, patients experienced typical cancer treatment side effects, such as fatigue, nausea, and lower blood cell counts, but could usually manage them with proper care.

Overall, current findings suggest that volrustomig is safe enough for further testing in trials like this one. The goal is to evaluate its effectiveness and monitor any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for non-small cell lung cancer, which often include chemotherapy alone, Volrustomig introduces a new approach by combining with chemotherapy and targeting specific cancer pathways. Researchers are excited about Volrustomig because it works by augmenting the body's immune response to attack cancer cells more effectively. The unique combination of Volrustomig with carboplatin and pemetrexed, or with additional agents like ramucirumab and paclitaxel, aims to enhance the overall effectiveness of treatment, potentially leading to better outcomes for patients.

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

Research has shown that volrustomig may help treat non-small cell lung cancer (NSCLC). In this trial, participants will receive different dosing regimens of volrustomig combined with chemotherapy. Studies have found that volrustomig, when used with chemotherapy, can block certain proteins (PD-1 and CTLA-4) that usually help cancer cells evade the immune system. This allows the immune system to better fight the cancer. In one study, patients with advanced NSCLC experienced a significant reduction in tumor size when treated with volrustomig and chemotherapy. Early results also suggest that most patients generally manage the side effects. Overall, these findings suggest that volrustomig could be an effective treatment option for people with this type of lung cancer. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with a specific lung cancer (NSQ NSCLC) who weigh over 35 kg, have at least one measurable tumor, and are expected to live more than 12 weeks. They should be fairly active (ECOG status of 0 or 1), not have certain gene mutations in their cancer, and must have functioning organs and bone marrow.

Inclusion Criteria

My doctor expects me to live for at least 12 more weeks.

My organs and bone marrow are working well.

I weigh more than 35 kilograms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive volrustomig in combination with chemotherapy (Carboplatin and Pemetrexed) in one of two dosing regimens

Up to 2.4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Pemetrexed
• Volrustomig

Trial Overview The study tests the safety and effectiveness of Volrustomig combined with Carboplatin and Pemetrexed in treating lung cancer. It will look into how the body processes these drugs, any potential immune responses to them, and their ability to shrink tumors.

How Is the Trial Designed?

Group I: Substudy 2: Arm 2A: Volrustomig dose regimen 2 +Ramucirumab + Carboplatin + Pemetrexed or Paclitaxel Experimental Treatment 5 Interventions

Volrustomig priming dose + ramucirumab + histology-specific chemotherapy (carboplatin+ either pemetrexed or paclitaxel).

Group II: Substudy 1: Arm 1B: Volrustomig dose regimen 2 + Carboplatin and Pemetrexed Experimental Treatment 3 Interventions

Volrustomig priming dose followed by volrustomig dosing regimen 2 in combination with carboplatin and pemetrexed.

Group III: Substudy 1: Arm 1A: Volrustomig dose regimen 1 + Carboplatin and Pemetrexed Experimental Treatment 3 Interventions

Volrustomig priming dose followed by volrustomig dosing regimen 1 in combination with carboplatin and pemetrexed.

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

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]

Cadonilimab, an anti PD-1 and CTLA-4 bispecific antibody, showed limited efficacy in treating previously treated metastatic non-small-cell lung cancer (NSCLC), achieving an objective response rate of only 10% in patients who were immunotherapy naïve after platinum-based chemotherapy.

The treatment was well-tolerated, with only 11.3% of patients experiencing grade 3-4 adverse events, suggesting that cadonilimab could be a viable option for second-line therapy in NSCLC, particularly for those who have not previously received immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study). Zhao, Y., Ma, Y., Fan, Y., et al.[2023]

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]

The combination of anti-PD-1 and anti-CTLA4 antibodies has improved cancer treatment outcomes but is often limited by serious immune-related side effects and resistance.

MEDI5752, a new bispecific antibody targeting both PD-1 and CTLA4, aims to enhance treatment effectiveness by focusing on T cells that have already encountered antigens, potentially increasing efficacy while reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity. Burton, EM., Tawbi, HA.[2021]

The investigational bispecific DART molecule MGD019 effectively combines PD-1 and CTLA-4 blockade in a single treatment, showing promise for enhanced therapeutic effects in cancer by targeting tumor-infiltrating lymphocytes.

In a first-in-human study involving patients with advanced solid tumors, MGD019 demonstrated acceptable safety and pharmacodynamic evidence of dual blockade, leading to objective responses in tumor types that usually do not respond to standard checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. Berezhnoy, A., Sumrow, BJ., Stahl, K., et al.[2022]

The combination of PD-1/PD-L1 and CTLA-4 inhibitors significantly improves objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in patients with advanced lung cancer, based on a review of six studies.

While the incidence of severe adverse events (grade ≥3) was lower than in control groups, it was still notable, indicating that while the treatment is generally tolerable, monitoring for side effects remains important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of PD-1/PD-L1 plus CTLA-4 antibodies ± other therapies in lung cancer: a systematic review and meta-analysis. Shen, X., Huang, S., Xiao, H., et al.[2023]

The novel bispecific antibody (BsAb) targeting both RANKL and PD-1 showed strong anti-tumor activity in various cancer models, including those resistant to traditional immune checkpoint inhibitors, indicating its potential as an effective treatment option.

This BsAb not only retained the ability to block RANKL and PD-1 interactions but also demonstrated superior anti-tumor responses compared to separate treatments with anti-RANKL and anti-PD-1 antibodies, highlighting the benefits of simultaneous targeting in enhancing anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual targeting of RANKL and PD-1 with a bispecific antibody improves anti-tumor immunity. Dougall, WC., Roman Aguilera, A., Smyth, MJ.[2022]

In a phase 1b study involving 102 patients with advanced non-small cell lung cancer, the combination of durvalumab and tremelimumab demonstrated manageable safety, although 36% of patients experienced serious treatment-related adverse events, including three treatment-related deaths.

The treatment showed evidence of antitumor activity in both PD-L1-positive and PD-L1-negative tumors, with a confirmed objective response rate of 23% in the cohort receiving tremelimumab 1 mg/kg, indicating potential effectiveness regardless of PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Antonia, S., Goldberg, SB., Balmanoukian, A., et al.[2022]

MEDI5752 is a novel bispecific antibody that effectively targets PD-1+ activated T cells while modulating CTLA4 inhibition, potentially reducing the dose needed for immune activation compared to traditional therapies.

In early results, MEDI5752 showed promising efficacy in patients with advanced solid tumors, leading to robust partial responses, and it preferentially accumulates in tumors, enhancing its therapeutic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+ Activated T Cells. Dovedi, SJ., Elder, MJ., Yang, C., et al.[2022]

Citations

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

Services Unavailable 24+ Hours, Maintenance Info MEDI5752 is a monovalent bispecific immunotherapy and is strategically unique as it combines both anti programmed cell death 1 and anti cytotoxic ...

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

eVOLVE-Lung02: 1L volrustomig vs pembrolizumab in mNSCLC Outcomes to first-line pembrolizumab in patients with non-small cell lung cancer and a PD-L1 tumor proportion score ≥90%.

3. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/CT016/701946/Abstract-CT016-MEDI5752-a-novel-PD-1-CTLA-4

Abstract CT016: MEDI5752, a novel PD-1/CTLA-4 bispecific ... Results: At data cutoff (Sept 30, 2021), 86 pts (median age, 60.5 years; male, 75.6%; Asian, 57.0%) were enrolled. The most common tumor types ...

4. jto.org jto.org/article/S1556-0864(24)00936-5/fulltext

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

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

Study: Volrustomig vs Pembrolizumab for NSCLC 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 ... The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-small cell lung cancer: A multicenter retrospective ...

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 ... Background: MEDI5752 is a monovalent bispecific antibody targeting PD-1 and CTLA-4. A phase I, open-label study (NCT03530397) of MEDI5752 ...

9. 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 ...