A Study Evaluating Efficacy and Safety of Multiple Treatment Combinations in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (Morpheus-Head and Neck Cancer)

NCT ID: NCT05459129

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-12
• Study Completion Date: 2024-08-15

Brief Summary

This is a Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with locally advanced squamous cell carcinoma of the head and neck (SCCHN). The study will enroll treatment-naive participants with resectable Stage III-IVA human papillomavirus (HPV)-negative, programmed death-ligand 1 (PD-L1)-positive SCCHN with measurable disease, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) who have not received systemic treatment for their disease.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezo + Tira

Participants in the atezolizumab plus tiragolumab arm will receive treatment for two cycles (6 weeks) until surgery or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Group Type: ACTIVE_COMPARATOR

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Tiragolumab

Intervention Type: DRUG

Tiragolumab will be administered intravenously at a fixed dose of 600 mg on Day 1 of each 21-day cycle.

Atezo + Tira + CP

Participants in the atezolizumab plus tiragolumab plus carboplatin plus paclitaxel arm arm will receive treatment for two cycles (6 weeks) until surgery or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Tiragolumab

Intervention Type: DRUG

Tiragolumab will be administered intravenously at a fixed dose of 600 mg on Day 1 of each 21-day cycle.

Carboplatin

Intervention Type: DRUG

Carboplatin will be administered intravenously at a dose of area under the concentration-time curve (AUC) 5 mg/mL/min on Day 1 of each 21 day cycle.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered intravenously at a dose of 175 mg/m2 on Day 1 of each 21 day cycle.

Interventions

Atezolizumab

Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Intervention Type: DRUG

Tiragolumab

Tiragolumab will be administered intravenously at a fixed dose of 600 mg on Day 1 of each 21-day cycle.

Intervention Type: DRUG

Carboplatin

Carboplatin will be administered intravenously at a dose of area under the concentration-time curve (AUC) 5 mg/mL/min on Day 1 of each 21 day cycle.

Intervention Type: DRUG

Paclitaxel

Paclitaxel will be administered intravenously at a dose of 175 mg/m2 on Day 1 of each 21 day cycle.

Intervention Type: DRUG

Other Intervention Names

Tecentriq

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Histologically confirmed, resectable Stage III-IVA SCCHN
• Eligible candidate for R0 resection with curative intent at the time of screening
• HPV-negative test for oropharyngeal carcinoma, as determined locally by p16 immunohistochemistry (IHC), in situ hybridization, or polymerase chain reaction-based assay
• Measurable disease (at least one target lesion), as assessed according to RECIST v1.1
• PD-L1 expression, defined as a combined positive score (CPS) >= 1
• Adequate hematologic and end-organ function
• Negative HIV test with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load.
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb), Positive total hepatitis B core antibody (HBcAb) followed by a negative quantitative hepatitis B virus (HBV) DNA.

Exclusion Criteria

• HPV-positive oropharyngeal cancer, as determined locally by p16 IHC, in situ hybridization, or by polymerase chain reactions-based assay
• Distantly metastasized SCCHN
• Any prior therapy for SCCHN, including immunotherapy, chemotherapy, or RT
• Prior treatment with any of the protocol-specified study treatments
• Treatment with investigational therapy within 42 days prior to initiation of study treatment
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Prior allogeneic stem cell or solid organ transplantation
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT scan)
• History of malignancy other than SCCHN within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5 -year OS rate>90%)
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with therapeutic or prophylactic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment
• Significant cardiovascular disease such a New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhytmia, or unstable angina
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to study initiation of study treatment, or anticipation of need for a major surgical procedure other than tumor resection, during the study
• Any of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of investigational drug, may affect the interpretation of the results, impair the ability of the patient to participate in the study, or renders the patient at high risk form treatment complications
• History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
• Known allergy or hypersensitivity to any of the study drugs or their excipients
• Known intolerance to any of the drugs required for premedication
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study
• Eligible only for the control arm
• Active EBV infection or known or suspected chronic EBV infection at screening

• Known severe allergy or hypersensitivity to placlitaxel, platinum or platinum-containing compounds
• Known history of severe hypersensitivity to products containing Cremophor EL
• Creatinine clearance <45m./min (Calculated using the Cockcroft-Gault formula)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope

Duarte, California, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Hadassah University Hospital - Ein Kerem

Jerusaelm, , Israel

Severance Hospital - Yonsei Cancer Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Countries

United States; Israel; South Korea

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CO43613

Identifier Type: -

Identifier Source: org_study_id