AZD2936 for Head and Neck Cancer

(MERIDIAN Trial)

Overseen By Minge Xu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Metastasis, Autoimmune disorders, Infections, 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: 21

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how effectively AZD2936 clears leftover cancer markers in the blood after standard treatment for a type of head and neck cancer. Researchers are testing AZD2936, an experimental treatment, alongside Cetuximab and Monalizumab to determine which is most effective. This trial targets patients with high-risk head and neck cancer who still show cancer signals in their blood after primary treatments. Participants should have already undergone treatments like surgery or radiation and still have detectable traces of cancer in their blood. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot use any concurrent anticancer treatment or immunosuppressive medication within 14 days before starting the study. It's best to discuss your current medications with the study team.

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

Research shows that Cetuximab, one of the treatments under study, has been safely used to treat various cancers, including head and neck cancer. Most patients tolerate it well. The FDA has approved Cetuximab for certain conditions, which supports its safety profile.

For AZD2936, another treatment being tested, detailed safety information remains limited. However, this trial is in Phase 2, indicating that earlier studies likely demonstrated sufficient safety for broader testing. Before reaching this phase, researchers ensure treatments do not cause serious side effects.

Overall, current evidence suggests these treatments are safe enough for further study in humans. It is important to remember that all treatments can have side effects, and participating in a trial means these risks will be closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD2936 for head and neck cancer because it offers a fresh approach by targeting specific cancer cells with precision. Unlike traditional treatments that attack both cancerous and healthy cells, AZD2936 is designed to selectively target tumor cells, potentially leading to fewer side effects. This investigational treatment is administered via IV infusion, ensuring direct delivery into the bloodstream, which might enhance its effectiveness. Additionally, AZD2936's novel formulation as a liquid drug product could allow for a more tailored dosing regimen, potentially improving patient outcomes compared to existing options like chemotherapy and radiation.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research shows that AZD2936, a special type of antibody, holds early promise in treating advanced cancers. In this trial, some participants will receive AZD2936, which studies have found to be both safe and effective, with some patients experiencing significant improvements. For individuals with head and neck cancer, AZD2936 has slowed tumor growth without causing serious side effects from radiation therapy. However, reports of serious skin reactions exist, so discussing potential risks with a healthcare provider is important. Overall, AZD2936 offers hope, especially for patients who haven’t responded to other treatments. ^{2 5 6 7 8}

Who Is on the Research Team?

Lillian Siu, MD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults with advanced head and neck squamous cell carcinoma (LA-HNSCC) who have detectable cancer DNA in their blood after initial treatment. They must be able to perform daily activities with ease or with some limitation (ECOG 0-1), weigh at least 35 kg, and have a life expectancy of over 12 weeks.

Inclusion Criteria

My head or neck cancer is either high-risk HPV positive or negative.

I weigh at least 35 kilograms.

My cancer in the head or neck area has been confirmed by lab tests.

Exclusion Criteria

I have or had an autoimmune or inflammatory disorder.

My cancer has spread to distant parts of my body.

Participation in another clinical study with an investigational product administered in the last 28 days prior to randomization or concurrent enrollment in another clinical study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Definitive Treatment

Participants undergo definitive treatment which may include surgery followed by radiation or chemoradiation, or definitive radiation or chemoradiation according to standard of care.

Varies

Baseline ctDNA sample collection and CT staging before treatment

Post Definitive Treatment

ctDNA analysis performed at approximately week 5 and week 10 to classify patients as MRD positive or negative.

10 weeks

ctDNA analysis at week 5 and week 10

Randomized Interventional Treatment

MRD positive patients are randomized to receive AZD2936 or observation. Treatment continues until completion of 6 cycles, intolerable toxicity, or patient decision.

Varies

ctDNA analysis at week 10

Follow-up for MRD Positive

Follow-up for MRD positive patients with ctDNA samples analyzed at week 2 and week 10. Plasma samples collected every 6 months for 3 years.

3 years

Plasma samples every 6 months, CT/MRI at week 2

Observational Follow-up for MRD Negative

Observational follow-up for MRD negative patients with ctDNA sample collection at first follow-up and at progression if applicable.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Monalizumab

Trial Overview The study tests AZD2936's ability to clear molecular residual disease (MRD), which is cancer DNA found in the blood post-treatment, in patients with high-risk LA-HNSCC. It's an open-label phase II trial where around 200 participants will receive this experimental therapy.

How Is the Trial Designed?

Group I: MRD positive Cohort - Arm A (treatment) Experimental Treatment 1 Intervention

Dose formulation- AZD2936 is supplied as a liquid drug product in a 20R vial containing 750 mg (nominal) of active AZD2936. The solution contains 50 mg/mL AZD2936 in 20 mM L-histidine/L- histidine-hydrochloride, 240 mM sucrose, 0.04% (w/v) poloxamer 188, at pH 6.0. Unit dose strength(s)- 750 mg/vial (50 mg/mL) Dosage levels- 750mg administered Q3W Route of administration- IV infusion over 1 hour

Group II: MRD negative Cohort Active Control 1 Intervention

Observation

Group III: MRD positive Cohort - Arm B (observation) Active Control 1 Intervention

Observation

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

NeoGenomics Laboratories, Inc.

Collaborator

NeoGenomics Laboratories

Collaborator

Trials

1

Recruited

200+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

AstraZeneca

Industry 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 CIFRA study is investigating the effectiveness of cetuximab combined with irinotecan and fluorouracil in patients with metastatic colorectal cancer who have a specific genetic profile (FcγRIIIa V/V), which may enhance the drug's action through a mechanism called Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).

This phase II trial aims to determine if patients with the FcγRIIIa V/V genotype have a higher response rate to cetuximab, potentially improving treatment outcomes, while also assessing safety and survival metrics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. Ottaiano, A., Scala, S., Normanno, N., et al.[2020]

Monoclonal antibodies like cetuximab work by promoting receptor endocytosis and activating the immune system to reduce tumor growth in head and neck squamous cell carcinoma (HNSCC).

Different strategies for targeting EGFR, including tyrosine kinase inhibitors and antisense approaches, have unique mechanisms of action, which could lead to more effective treatments and better patient selection for EGFR inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. Cassell, A., Grandis, JR.[2021]

Adding the EGFR inhibitor cetuximab to radiotherapy for locally advanced squamous cell carcinoma of the head and neck significantly improves clinical outcomes without increasing the toxicity associated with radiotherapy.

Current chemoradiotherapy regimens, which are often platinum-based, have reached a limit in tolerable toxicity, highlighting the need for more effective and tolerable treatment options like cetuximab combined with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck? Bernier, J., Schneider, D.[2015]

The ERBITAX regimen (paclitaxel and cetuximab) demonstrated a response rate of 37.7% in 531 patients with recurrent/metastatic squamous cell carcinoma of the head and neck who were ineligible for cisplatin-based chemotherapy, indicating its efficacy as a first-line treatment.

Patients who received immunotherapy after ERBITAX treatment had significantly improved overall survival (OS) of 29.8 months compared to 13.8 months for those receiving other treatments, suggesting a beneficial sequential treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck. Rubió-Casadevall, J., Cirauqui Cirauqui, B., Martinez Trufero, J., et al.[2023]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

In a study of 99 head-and-neck cancer patients receiving simultaneous integrated boost intensity-modulated radiotherapy with cetuximab, 34% experienced severe dermatitis (Grade 3/4), significantly higher than the 3% in a control group treated with cisplatin.

There was a clear link between the radiation dose to the skin and the severity of dermatitis in patients receiving cetuximab, indicating that higher radiation exposure increases the risk of severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Studer, G., Brown, M., Salgueiro, EB., et al.[2015]

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

In a study of 32 head and neck squamous cell carcinoma (HNSCC) cell lines, researchers identified YAP1 amplification as a key factor associated with resistance to the EGFR-targeting antibody cetuximab, suggesting it could serve as a novel biomarker for treatment response.

The study demonstrated that higher levels of YAP1 not only correlated with cetuximab resistance but also that reducing YAP1 expression through RNA knockdown increased sensitivity to the drug, highlighting its potential role in guiding therapy decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer. Jerhammar, F., Johansson, AC., Ceder, R., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-2-squamous-cell-carcinoma-of-head-and-neck-6-2022-88bb0

AZD2936 for Head and Neck Cancer (MERIDIAN Trial) In some studies, it was shown to be effective without increasing radiotherapy-related side effects, but serious skin reactions have been reported in head and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1053429625000098

Metastatic Head and Neck Cancer: Immunotherapy and ... KEYNOTE-B10 results showed similar efficacy with a response rate of 49% (95% CI 38.4-58.7), median PFS 5.6 months (95% CI 5.1-6.7), and OS 13.1 months (95% CI ...

3. pryzm.ozmosi.com pryzm.ozmosi.com/product/22450

Rilvegostomig Drug Profile Clinical Outcomes Reported - AstraZeneca presented P3 Oncology Solid Tumor Unspecified results on 2025-05-31 for Rilvegostomig · Clinical Outcomes Reported - ...

4. s3.amazonaws.com s3.amazonaws.com/files.oncologymeetings.org/prod/s3fs-public/2024-05/AM24-Head-Neck%20Cancer.pdf

Head and Neck Cancer Exploratory endpoints included efficacy outcomes by HER2 expression. Results: At data cutoff. (June 2023), 24 pts with head and neck tumors (n=19 salivary ...

5. onclive.com onclive.com/view/tigit-pd-1-bispecific-rilvegostomig-shows-promise-following-prior-immunotherapy-resistance-for-advanced-pd-l1-nsclc

TIGIT, PD-1 Bispecific Rilvegostomig Shows Promise ... The PD-1 and TIGIT bispecific rilvegostomig (AZD2936) demonstrated promising early signs of tolerability and efficacy in patients with advanced or metastatic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06366451

Study Details | NCT06366451 | PBI-MST-01 ... This is a multi-center, open-label, Phase 0 substudy designed to evaluate the localized pharmacodynamics (PD) of rilvegostomig, volrustomig, sabestomig, ...

7. medchemexpress.com medchemexpress.com/rilvegostomig.html?srsltid=AfmBOooExePthovlG-Hp878-NJD-aFqXhhewItpZag9_RgmFuHI0QMx3

Rilvegostomig (AZD-2936) | Anti-PDCD1/TIGIT Antibody Rilvegostomig is an anti-PDCD1/TIGIT human IgG1 κ monoclonal antibody. Recommend Isotype Controls: Human IgG1 kappa, Isotype Control (HY-P99001).

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS6122

Molecular residual disease (MRD) interception in ... Molecular residual disease (MRD) interception in locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC): MERIDIAN study.