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

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

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity Health Network, Toronto

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

Histological or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including participants with p16-negative squamous cell carcinoma of unknown primary or non-squamous histologies (eg, nasopharynx, paranasal sinus or salivary gland).

Any unresolved toxicity NCI CTCAE ≥ Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with AZD2936 may be included only after consultation with the Principal Investigator.

Evidence of distant metastasis in staging.

History of allogeneic organ transplantation.

Trial design

Design model

Parallel

Treatments tested in this trial

AZD2936
Biological/Vaccine
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.

Treatment groups

102 Participants

are divided into 2 treatment groups

Group A: MRD positive and/or radiological/clinical progression CohortExperimental treatment 1 intervention

Group B: MRD negative CohortNo intervention 0 interventions

Trial outcomes

Primary outcomes

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.

Time frame

3 years

Secondary outcomes

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.

Disease free survival (DFS) at 12 months.

Time frame

3 years

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

Time to MRD control failure in MRD+ patients. MRD control failure is defined as two consecutive increases in ctDNA levels (week 2 and week 10 in Part D).

Time frame

3 years

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

Median DFS and OS in MRD+ patients.

Time frame

3 years

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

* Number and severity of treatment related adverse events according to CTCAE v5.0. * Percentage of participants with AEs, SAEs and rate of AZD2936 discontinuation due to toxicity.

Time frame

3 years

Other outcomes

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).

• Changes in HPV DNA in MRD+ HPV+ patients treated with AZD2936 or under observation and correlation of such changes with DFS.

Time frame

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).

Changes in methylated ctDNA in MRD+ patients treated with AZD2936 or under observation, and correlation of such changes with bespoke ctDNA and with DFS.

Time frame

3 years

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

Changes in quantitative bespoke ctDNA and HPV DNA measurements before treatment and at W4-6 and W 8-12 (Parts A and B).

Time frame

2 years

Kinetics of bespoke ctDNA and HPV DNA in MRD+ LA-HNSCC patients who are treated with AZD2936 compared to observation (SOC).

Changes in quantitative bespoke ctDNA and HPV DNA measurements during and after treatment/observation (Parts C and D).

Time frame

3 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Health Network, Toronto

Lead sponsor

AstraZeneca

Collaborator

NeoGenomics Laboratories, Inc.

Collaborator

Personalis Inc.

Collaborator

Source ClinicalTrials.gov

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