Volrustomig for Advanced Throat Cancer

(eVOLVE-HNSCC Trial)

Recruiting in Palo Alto (17 mi)

+210 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Disqualifiers: Other head/neck cancer, Residual disease, Recurrent LA-HNSCC, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing volrustomig, a medication, in patients with a specific type of head and neck cancer that hasn't worsened after standard treatment. The goal is to see if volrustomig can help stop the cancer from growing.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug Volrustomig for advanced throat cancer?

Preliminary data from a phase I trial of MEDI5752, which targets both PD-1 and CTLA-4, shows that the drug is well tolerated and active, with lasting responses in various cancer types. This suggests potential effectiveness for advanced throat cancer as well. ^{1 2 3 4 5}

Is Volrustomig (MEDI-5752) safe for humans?

Preliminary data from a phase I trial of MEDI5752, which targets both PD-1 and CTLA4, indicate that the drug is generally well tolerated in humans, with durable responses seen across various tumor types. ^{1 3 4 6 7}

How is the drug Volrustomig different from other treatments for advanced throat cancer?

Volrustomig is unique because it is a bispecific antibody that targets two immune checkpoints, PD-1 and CTLA-4, in a single molecule. 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 2 4 8 9}

Research Team

Robert Haddad, MD

Principal Investigator

Dana Farber Cancer Institute Massachusetts, USA

Lisa Licitra, MD

Principal Investigator

Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan Milan, Italy

Eligibility Criteria

This trial is for adults with advanced head and neck squamous cell carcinoma that hasn't spread elsewhere. They should have completed treatment with chemo and radiation within the last 12 weeks without surgery, aiming to cure.

Inclusion Criteria

I finished my combined chemotherapy and radiation treatment for cancer less than 12 weeks ago.

My cancer is at an advanced stage and cannot be surgically removed.

My cancer is in the throat or mouth area and hasn't spread elsewhere.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive volrustomig or undergo observation following definitive concurrent chemoradiotherapy

Up to approximately 7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 7 years

Treatment Details

Interventions

• Volrustomig (Monoclonal Antibodies)

Trial Overview The study tests Volrustomig's effectiveness and safety against no further treatment after standard chemoradiotherapy in patients whose cancer remains but hasn't worsened or spread.

Participant Groups

Group I: Study Arm Experimental Treatment 1 Intervention

Participants in this arm will receive volrustomig.

Group II: Observation Arm Active Control 1 Intervention

Patients in this arm will undergo observation.

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]

A novel bispecific antibody, BiAb-1, effectively targets both PD-L1 and TIGIT, showing enhanced binding and cytokine production, which may improve immune responses against tumors.

BiAb-1 demonstrated superior anti-tumor efficacy compared to traditional PD-1/PD-L1 inhibitors in multiple tumor models, suggesting it could be a promising new treatment option for cancer patients resistant to current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of a novel anti PD-L1 X TIGIT bispecific antibody for the treatment of solid tumors. Xiao, Y., Chen, P., Luo, C., et al.[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]

The bispecific antibody PD-L1xEGFR selectively targets PD-L1 on EGFR-expressing cancer cells, significantly enhancing the reactivation of anticancer T cells while reducing the risk of autoimmune side effects associated with traditional PD-L1-blocking antibodies.

In preclinical models, PD-L1xEGFR demonstrated a 140-fold greater potency in blocking PD-L1 on cancer cells compared to a control antibody, leading to improved T cell activation and tumor uptake, suggesting it could enhance both efficacy and safety in treating EGFR-overexpressing cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint. Koopmans, I., Hendriks, D., Samplonius, DF., et al.[2021]

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]

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]

Ertumaxomab, a bispecific antibody targeting HER2/neu and CD3, was found to be safe at doses up to 100 micrograms, with most side effects being mild and reversible, although some patients experienced more serious adverse events.

In a study of 17 patients with metastatic breast cancer, 5 showed an antitumor response at doses of 100 micrograms or higher, indicating potential efficacy in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. Kiewe, P., Hasmüller, S., Kahlert, S., et al.[2020]

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. England pubmed.ncbi.nlm.nih.gov

Discovery of a novel anti PD-L1 X TIGIT bispecific antibody for the treatment of solid tumors. [2022]

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

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

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

Bispecific Targeting of PD-1 and PD-L1 Enhances T-cell Activation and Antitumor Immunity. [2021]

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

A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint. [2021]

7. 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]

8. 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]

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

Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. [2020]