Volrustomig for Advanced Throat Cancer

(eVOLVE-HNSCC Trial)

Recruiting at 281 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: Other head/neck cancer, Residual disease, Recurrent LA-HNSCC, 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 7 years

1145 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called volrustomig (a PD-1/CTLA-4 bispecific monoclonal antibody) for individuals with advanced throat cancer who have already undergone chemoradiotherapy. The researchers aim to determine if volrustomig is more effective and safer than monitoring the cancer without additional treatment. Participants are divided into two groups: one receives the new treatment, while the other is under observation. This trial targets those with specific types of throat cancer that haven't spread and who have completed earlier treatment aimed at curing the cancer. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that volrustomig is likely to be safe for humans?

Research has shown that volrustomig is generally safe for people. Early study results indicated that this treatment, which targets specific proteins on cancer cells, did not cause serious side effects for most patients. Some people experienced mild reactions, but these were manageable. As this trial is in a later stage, substantial information about its safety already exists. Overall, the treatment appears to be safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced throat cancer, which often include surgery, radiation, and chemotherapy, Volrustomig offers a new approach by targeting specific cancer cell markers with precision. This novel mechanism of action means it could potentially attack cancer cells more directly, sparing more healthy tissue compared to traditional methods. Researchers are particularly excited about Volrustomig because it might reduce side effects and improve quality of life for patients, while also enhancing treatment effectiveness.

What evidence suggests that volrustomig might be an effective treatment for advanced throat cancer?

Research has shown that volrustomig, which participants in this trial may receive, could be a promising treatment for advanced throat cancer. It targets two proteins, PD-1 and CTLA-4, to help the immune system fight cancer. Studies have found that targeting these proteins together can strengthen the body's defense against tumors. Early results suggest volrustomig has improved outcomes in other cancers, such as kidney cancer. While specific data for throat cancer is still being gathered, the mechanism of volrustomig offers hope for positive results. ^{1 2 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Volrustomig

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

LY3434172, a bispecific antibody targeting both PD-1 and PD-L1, showed enhanced T-cell activation and antitumor activity in vitro compared to existing therapies that target these pathways individually.

In mouse models with human immune cells, LY3434172 demonstrated significantly stronger antitumor effects than either the anti-PD-1 or anti-PD-L1 antibodies alone, suggesting its potential as a novel cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Targeting of PD-1 and PD-L1 Enhances T-cell Activation and Antitumor Immunity. Kotanides, H., Li, Y., Malabunga, M., et al.[2021]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS6120

eVOLVE-HNSCC: A global phase 3 study of volrustomig as ... The phase 3, randomized, open-label, multicenter, eVOLVE-HNSCC study will evaluate the efficacy and safety of sequential therapy with volrustomig compared with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06129864

NCT06129864 | A Global Study of Volrustomig (MEDI5752) ... The main purpose of this study is to assess the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced ...

3. urotoday.com urotoday.com/conference-highlights/esmo-2023/esmo-2023-kidney-cancer/147556-esmo-2023-medi5752-volrustomig-a-novel-pd-1-ctla-4-bispecific-antibody-in-the-first-line-1l-treatment-of-65-patients-pts-with-advanced-clear-cell-renal-cell-carcinoma-arcc.html

ESMO 2023: MEDI5752 (Volrustomig), a Novel PD-1/CTLA ... Volrustomig has the potential to improve outcomes in patients with advanced RCC. Presented by: Martin Voss, MD, Clinical Director ...

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

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 cytotoxic ...

5. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D798EC00001

A global study of volrustomig (MEDI5752) for participants ... The main purpose of this study is to assess the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced ...

6. withpower.com withpower.com/trial/phase-3-carcinoma-10-2023-5d949

Volrustomig for Advanced Throat Cancer 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 ...

7. uclahealth.org uclahealth.org/clinical-trials/global-study-volrustomig-medi5752-participants-with

A Global Study of Volrustomig (MEDI5752) for Participants ... The main purpose of this study is to assess the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced ...

8. clinicaltrials.eu clinicaltrials.eu/inn/volrustomig/

Volrustomig: A Promising New Cancer Treatment Volrustomig is being studied for the treatment of several types of cancer, including: Head and Neck Squamous Cell Carcinoma (HNSCC): A type of cancer that ...