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)

NCT05459129 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CO43613
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 6

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Pathologic Complete Response (pCR) as Determined by Local Pathologic Review

  pCR was defined as the absence of any viable primary tumor at time of surgical resection, as determined by local pathologic review. The pCR rate was defined as the percentage of participants who achieved a pCR. pCR rate was calculated for each arm, along with the 95% confidence interval (CI) estimated using the Clopper-Pearson method and the 95% CI for difference in rates was estimated using the Wald method with continuity correction. Participants with missing or no pathologic response assessment were classified as non-responders. Percentages have been rounded off to the nearest whole number.

  At the time of surgery (Week 7 ± 1 week)

Secondary Outcomes (13)

• Pathologic Response Rate (pRR) as Determined by Local Pathologic Review

  At the time of surgery (Week 7 ± 1 week)

• Event-Free Survival (EFS)

  From randomization to PD disease recurrence or death (Up to 9.2 months)

• Relapse-Free Survival (RFS)

  From surgery (scheduled at Week 7 ± 1 week) to first documented disease recurrence or death (up to 7.6 months)

• Overall Survival (OS)

  From randomization to death from any cause or last known to be alive (Up to 9.2 months)

• Objective Response Rate (ORR)

  Prior to surgery (up to Week 6)

Study Arms (2)

Atezo + Tira

ACTIVE COMPARATOR

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.

Drug: Atezolizumab; Drug: Tiragolumab

Atezo + Tira + CP

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Atezolizumab DRUG

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

Also known as: Tecentriq

Atezo + Tira; Atezo + Tira + CP

Tiragolumab DRUG

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

Atezo + Tira; Atezo + Tira + CP

Carboplatin 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.

Atezo + Tira + CP

Paclitaxel DRUG

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

Atezo + Tira + CP

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Hadassah University Hospital - Ein Kerem

Jerusaelm, 9112001, Israel

Location

Severance Hospital - Yonsei Cancer Center

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

atezolizumab; Tiragolumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: July 14, 2022
• Study Start: April 12, 2023
• Primary Completion: August 15, 2024
• Study Completion: August 15, 2024
• Last Updated: September 15, 2025
• Results First Posted: September 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

IL (1); US (3); KR (2)