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)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05459129

Collaborator

(none)

180

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Drug: Atezolizumab Drug: Tiragolumab Radiation: Immune-modulating stereotactic radiotherapy (iSBRT) Drug: Carboplatin Drug: Paclitaxel	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The 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)

Anticipated Study Start Date :

Sep 30, 2022

Anticipated Primary Completion Date :

Aug 29, 2025

Anticipated Study Completion Date :

Aug 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Atezo Monotherapy Particiapnts in the atezo monotherapy 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 Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Other Names: Tecentriq
Experimental: 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.	Drug: Atezolizumab Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Other Names: Tecentriq Drug: Tiragolumab Tiragolumab will be administered intravenously at a fixed dose of 600 mg on Day 1 of each 21-day cycle.
Experimental: Atezo + Tira +iSBRT Participants in the atezolizumab plus tiragolumab plus RT 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 Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Other Names: Tecentriq Drug: Tiragolumab Tiragolumab will be administered intravenously at a fixed dose of 600 mg on Day 1 of each 21-day cycle. Radiation: Immune-modulating stereotactic radiotherapy (iSBRT) iSBRT will be delivered 8 Gy x 3 doses between Days 2 and 21 of Cycle 1.
Experimental: 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.	Drug: Atezolizumab Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Other Names: Tecentriq Drug: Tiragolumab Tiragolumab will be administered intravenously at a fixed dose of 600 mg on Day 1 of each 21-day cycle. 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. Drug: Paclitaxel Paclitaxel will be administered intravenously at a dose of 175 mg/m2 on Day 1 of each 21 day cycle.

Outcome Measures

Primary Outcome Measures

Pathologic Complete Response (pCR), as Determined by Central Pathologic Review [At the time of surgery (Week 7)]
pCR is defined as the absence of any viable primary tumor at time of surgical resection, as determined by central pathologic review.

Secondary Outcome Measures

pCR, as Determined by Local Pathologic Review [At the time of surgery (Week 7)]
pCR is defined as the absence of any viable primary tumor at time of surgical resection, as determined by local pathologic review.
Pathologic Response Rate (pRR), as Determined by Central Pathologic Review and Local Pathologic Review [At the time of surgery (Week 7)]
pRR is defined as the proportion of participants with a pCR, mPR (defined as <=10% residual viable tumor at the time of surgical resection in the primary tumor) and pPR (defined as <50% residual viable tumor at the time of surgical resection in the primary tumor).
Event-Free Survival (EFS) [Randomization up to approximately 5 years]
EFS is defined as the time from randomization to any of the following events (whichever occurs first): disease progression that precludes surgery, as determined by the investigator according to RECIST v1.1, local, regional, or distant disease recurrence, or death from any cause.
Relapse-Free Survival (RFS) [Surgery up to approximately 5 years]
RFS is defined as the time from surgery to the first documented recurrence of disease or death from any cause.
Overall Survival (OS) [Randomization up to approximately 5 years]
OS is defined as the time from randomization to death from any cause.
Objective Response Rate (ORR) [After completion of neoadjuvant treatment (Week 7)]
ORR is defined as the proportion of patients with a complete response or a partial response, as determined by the investigator according to RECIST v1.1, prior to surgery.
Percentage of Participants With Adverse Events [Up to 5 years after first participant enrolled]
Percentage of participants with adverse events.
Percentage of Participants with Immune-Related Adverse Events Grade >=3 [Up to Week 12 after first participant enrolled]
Percentage of immune-related adverse events Grade >=3
Rate of Delayed Surgery Due to Treatment-Related Adverse Events [2 weeks after surgery (up to Week 9)]
Duration of Delayed Surgery Due to Treatment-Related Adverse Events [2 weeks after surgery (up to Week 9)]
Surgical Complication Rates [From surgery through follow-up (up to approximately 5 years)]
Surgical complications will be scored according to Clavien-Dindo classification.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, negative hepatitis B surface antibody (HBsAb) and negative total hepatitis B core antibody (HBcAb) test, negative hepatitis C virus (HCV) at screening

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