A Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck

Hoffmann-La Roche123 enrolled

Overview

The primary objective of this study is to evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo as first-line (1L) treatment in recurrent/metastatic PD-L1-positive squamous cell carcinoma of the head and neck (SCCHN) on the basis of confirmed objective response rate. In addition, safety, pharmacokinetics, immunogenicity of atezolizumab and tiragolumab will be evaluated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

123

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

AtezolizumabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Histologically or cytologically confirmed recurrent/metastatic SCCHN involving the oropharynx, oral cavity, larynx, or hypopharynx, that is considered incurable by local therapies * Known results from human papillomavirus (HPV) status test for oropharyngeal carcinoma * No prior systemic therapy for metastatic and/or recurrent SCCHN * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Tumor PD-L1 expression as determined by PD-L1 immunohistochemistry assay * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Life expectancy \>=12 weeks Key Exclusion Criteria: * Disease suitable for local therapy with curative intent * Progressive or recurrent disease within 6 months of the last dose of curative intent systemic treatment for locally advanced SCCHN * Rapidly progressing disease in the opinion of the treating investigator * Grade \>=2 unresolved toxicity related to surgery or other prior therapies * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * History of leptomeningeal disease * 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 additional malignancy other than SCCHN within 5 years prior to randomization * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-TIGIT, anti-PD-L1, and anti-PD-1 therapeutic antibodies * Treatment with systemic immunostimulatory agents or systemic immunosuppressive medication * Pregnancy or breastfeeding

Locations (47)

Moores Cancer Center at UC San Diego Health

La Jolla, California, United States

UCLA

Los Angeles, California, United States

SCRI Florida Cancer Specialists PAN

Tallahassee, Florida, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Percentage of Participants With Confirmed Objective Response, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

A confirmed objective response rate (ORR) was defined as the percentage of participants with a confirmed objective response (OR), characterized by a complete response (CR) or a partial response (PR), on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.

Time frame: Up to approximately 30.6 months

Secondary Outcomes

Duration of Response (DOR)

DOR was defined as the time from the first occurrence of a documented confirmed OR to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Confirmed OR was defined as either a CR or a PR on 2 consecutive occasions ≥ 4 weeks apart. CR was defined as disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Kaplan-Meier (K-M) method was used to estimate the median DOR.

Time frame: From first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 30.6 months)

Progression-free Survival (PFS)

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate the median PFS.

Time frame: From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 30.6 months)

Overall Survival (OS)

OS was defined as the time from randomization to death from any cause. K-M method was used to estimate the median OS.

Time frame: From randomization to death from any cause (up to approximately 30.6 months)

PFS Rate at 6 Months

PFS rate at 6 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by the investigator, at Month 6. PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate the PFS rate. Percentages have been rounded off.

Time frame: Month 6

OS Rate at 6 Months and 12 Months

OS rate at 6 months and 12 months was defined as percentage of participants who did not experience death from any cause at the specified timepoints. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off.

Time frame: Months 6 and 12

Time to Confirmed Deterioration (TTCD) in Participant-reported Physical Functioning (PF), as Measured by the Patient-reported Outcomes Measurement Information System (PROMIS) Item Bank Version 2.0 (v2.0)-PF-Short Form 10b

TTCD=time from the date of randomization to the first confirmed clinically meaningful deterioration (CCMD). PROMIS Item Bank v2.0-PF- Short Form 10b is a 10-item participant-reported questionnaire including 2 types of items to assess PF: 6 ability-based items assessing difficulty in performing activities, scored on a 5-point scale ranging from 1=Unable to do, 2=With much difficulty, 3=With some difficulty, 4=With a little difficulty, 5=Without any difficulty; and 4 limitation-based items assessing the extent to which health limits activities, scored on a 5-point scale ranging from 1=Cannot do, 2=Quite a lot, 3=Somewhat, 4=Very little, 5=Not at all. Item responses were summed to generate a raw score and converted to a PROMIS T-score, with a higher T-score indicating better PF. CCMD=decrease from baseline (≥ 4 points) in T-score, held for at least 2 consecutive assessments. K-M method was used to estimate median TTCD.

Time frame: Up to approximately 30.6 months

Number of Participants With Adverse Events (AEs)

An AE was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE was therefore any of the following: Any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Time frame: From study start up to 90 days after last dose (up to approximately 52.9 months)

Serum Concentration of Atezolizumab at Specified Timepoints

Time frame: Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/early discontinuation (ED) (1 Cycle=21 days) (up to approximately 49.9 months)

Serum Concentration of Tiragolumab at Specified Timepoints

Time frame: Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/ED (1 Cycle=21 days) (up to approximately 49.9 months)

Number of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab

Participants were considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following atezolizumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 0.60 titer unit (t.u.) greater than the baseline titer result (treatment-enhanced ADA response).

Time frame: Up to approximately 49.9 months

Number of Participants With ADAs to Tiragolumab

Participants were considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following tiragolumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 0.60 t.u. greater than the baseline titer result (treatment-enhanced ADA response).

Time frame: Up to approximately 49.9 months