Volrustomig + Chemotherapy for Non-Small Cell Lung Cancer

(eVOLVE-01 Trial)

Recruiting at 60 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

120 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Volrustomig + Chemotherapy for Non-Small Cell Lung Cancer?

Preliminary data from a phase I trial of MEDI5752, a bispecific antibody targeting both PD-1 and CTLA4, shows it is well tolerated and active, with durable responses across diverse tumor types. Additionally, combination immunotherapy with antibodies against PD-1 and CTLA-4 has shown improved clinical benefits across cancer types compared to single agents. ^{1 2 3 4 5}

Is the combination of Volrustomig (MEDI5752) and chemotherapy safe for humans?

Preliminary data from a phase I trial of MEDI5752, a bispecific antibody targeting both PD-1 and CTLA4, indicate the drug is well tolerated and active, with durable responses seen across diverse tumor types. This suggests that MEDI5752 may be generally safe in humans. ^{1 2 4 5 6}

What makes the drug Volrustomig unique for treating non-small cell lung cancer?

Volrustomig is unique because it is a bispecific antibody that targets two immune checkpoints, PD-1 and CTLA-4, simultaneously. This design allows it to enhance the immune response against cancer cells more effectively than using separate drugs for each target, potentially leading to better outcomes with fewer side effects. ^{1 4 7 8 9}

What is the purpose of this trial?

Purpose of this study is to assess the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of volrustomig in combination with other anticancer drugs in participants with specified solid tumors.

Eligibility Criteria

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 organs and bone marrow are working well.

I weigh more than 35 kilograms.

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

Timeline

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

Treatment Details

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.

Participant Groups

Group I: 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.

Group II: Arm 1 B 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.

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

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]

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]

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]

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]

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]

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]

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]

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 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]

References

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Dual targeting of RANKL and PD-1 with a bispecific antibody improves anti-tumor immunity. [2022]

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

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. [2022]

4. United States 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. [2022]

5. Ireland 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). [2023]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. [2022]

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

Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). [2022]

9. England 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. [2023]