Molecular Residual Disease Interception in Locoregionally-Advanced High Risk HPV+ and HPV- HNSCC

NCT05414032 | Recruiting Phase 2 DMC

• 1 other identifier: MERIDIAN
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, open-label study to assess the efficacy of AZD2936 in terms of molecular residual disease (MRD) clearance and treatment outcome in patients with MRD after definitive treatment for high risk locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). MRD is defined as ctDNA detection in plasma after definitive treatment. Approximately 100 patients are expected to be enrolled.

Conditions

Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC)

Outcome Measures

Primary Outcomes (1)

• Efficacy (in terms of ctDNA clearance) of AZD2936 compared to observation (Standard of Care, SOC) in LA-HNSCC patients who have MRD (MRD+) after definitive treatment.

  Clearance of bespoke ctDNA at different time points (week 2 and week 10 after the end of MRD treatment). ctDNA clearance is defined as no detection of ctDNA in both of these two consecutive determinations.

  3 years

Secondary Outcomes (4)

• Efficacy (in terms of delaying or preventing radiological recurrence of disease or death) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.

  3 years

• Efficacy (in terms of MRD control) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.

  3 years

• Efficacy (in terms of median DFS and OS) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.

  3 years

• Safety and tolerability of AZD2936 in MRD+ LA-HNSCC patients after definitive treatment and randomized to receive this combination.

  3 years

Other Outcomes (14)

• Predictive value (in terms of predicting radiological recurrence of disease or death) of HPV DNA in patients with HPV positive LA-HNSCC treated with AZD2936 compared to observation (SOC).

  3 years

• Predictive value (in terms of predicting radiological recurrence of disease or death) of methylated ctDNA in MRD+ LA-HNSCC patients treated with AZD2936 compared to observation (SOC).

  3 years

• Kinetics of bespoke ctDNA and HPV DNA in LA-HNSCC patients after definitive therapy

  2 years

Study Arms (2)

MRD positive and/or radiological/clinical progression Cohort

EXPERIMENTAL

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

Biological: AZD2936

MRD negative Cohort

NO INTERVENTION

Observation

Interventions

AZD2936 BIOLOGICAL

AZD2936 is a monovalent, bispecific, humanized, IgG1 triple mutant mAb antibody against human PD 1 and TIGIT. AZD2936 was constructed on the backbone of the DuetMab molecule (Mazor et al., 2015), and its antigen binding fragment portions are comprised of the variable domains of the anti TIGIT COM902 antibody and anti PD 1 LO115 antibody. The IgG1 Fc domain carries the triple mutation (L234F/L235E/P331S) designed to reduce Fc mediated immune effector functions. In the preclinical studies, dual blockade of TIGIT and PD 1 by AZD2936 enhanced human T cell function and promoted antitumor immune responses.

MRD positive and/or radiological/clinical progression Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of screening or age of consent according to law.
• Written informed consent and any locally required authorization (e.g., data privacy) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Weight ≥ 35 kg.
• Must have a life expectancy of at least 12 weeks.
• Histological or cytological confirmed LA-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx. Patients with locoregionally advanced unknown head and neck primary but tumor tested to be p16-positive are eligible.
• High-risk HPV negative LA-HNSCC patients (stage III-IVB according to AJCC/UICC 8th Edition) OR high-risk HPV positive LA-HNSCC patients (stage III according to AJCC/UICC 8th Edition).
• Archival tumor formalin-fixed, paraffin-embedded (FFPE) specimens for correlative biomarker studies are required (1 H\&E and 10 unstained 5 microns slides). If surgery is going to be performed after signing consent, then tumor FFPE from that surgery is allowed.
• Patient is a candidate for definitive treatment: either surgery followed by radiation or chemoradiation, OR definitive radiation, OR definitive chemoradiation.
• Objective radiological tumor response according to CT or MRI at 8-12 weeks after definitive therapy (surgery followed by radiation or chemoradiation, OR definite radiation, OR definite chemoradiation)
• ECOG performance status of 0 or 1 at randomization.
• Tumor must express PD-L1 (CPS ≥1) as determined by the local laboratory using the PD-L1 IHC 22C3 pharmDx assay.
• Detection of ctDNA in plasma samples collected in Part B in either:
• both samples collected at approximately week 5 (4-6) and at week 10 (8-12) OR
• only in the week 10 (8-12) sample NOTE: If ctDNA results at Week 10 are equivocal, a new sample should be collected and analyzed to confirm results within 4 weeks.

You may not qualify if:

• Any of the following would exclude the subject from participation in the study:
• Evidence of distant metastasis in staging.
• History of allogeneic organ transplantation.
• History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to AZD2936 or any of the excipients.
• History of active primary immunodeficiency.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], immune related diverticulitis \[prior diverticulitis in the context of diverticulosis is allowed provided is not active\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]).
• The following are exceptions to this criterion:
• Participants with vitiligo or alopecia
• Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy. Participants without active disease in the last 5 years may be included but only after consultation with the Principal Investigator
• Participants with celiac disease controlled by diet alone
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBV surface antigen \[HBsAg\] result), or hepatitis C(HCV) or acute hepatitis A. Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Also participants who have chronic hepatitis B and are receiving suppressive antiviral therapy are allowed to be enrolled if ALT is normal and viral load is controlled (\<100 U/ml by polymerase chain reaction). These patients must remain on antiviral therapy as per institutional practice during the study treatment and follow up period to ensure adequate viral suppression. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Patients with a known history of infection with human immunodeficiency virus (positive HIV 1/2 antibodies) are excluded. Testing in patients with no known history or no known risk factors is not required.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent.
• History of another primary malignancy except for:

Sponsors & Collaborators

• University Health Network, Toronto: lead
• AstraZeneca: collaborator
• NeoGenomics Laboratories, Inc.: collaborator
• Personalis Inc.: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Canada

RECRUITING

Study Officials

• Lillian Siu, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lillian Siu, MD

CONTACT

416-946-4501; tip@uhn.ca

Minge Xu

CONTACT

416-946-4501; Minge.Xu@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2022
• First Posted: June 10, 2022
• Study Start: July 12, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)