This is an open-label, multicenter, basket trial Phase II study to evaluate the antitumor activity of simlukafusp alfa in combination with atezolizumab in participants with advanced and/or metastatic solid tumors. Currently the focus is on participants with Head and Neck, oesophageal and cervical cancers with confirmed squamous cell carcinoma histology type.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
256
simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.
Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Single-agent treatment administered as per approved protocol.
Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR was defined as the percentage of participants with observed tumor response of complete response (CR), or partial response (PR) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The percentages of participants are rounded off to the nearest single decimal point.
Time frame: Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1
DCR was defined as the percentage of participants with observed tumor response of CR, PR or stable disease (SD) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir). The percentages of participants are rounded off to the nearest single decimal point.
Time frame: Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Duration of Response (DoR) According to RECIST Version 1.1
DoR was determined for participants who had a best overall response of CR or PR. CR was defined as the disappearance of all target lesions with a reduction in target/non-target pathological lymph nodes to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DoR was defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
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Single-agent treatment administered as per approved protocol.
University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Cancer Treatment Centers of America
Newnan, Georgia, United States
UZ Antwerpen
Edegem, Belgium
UZ Gent
Ghent, Belgium
UZ Leuven Gasthuisberg
Leuven, Belgium
Institut Bergonie
Bordeaux, France
Hopital Timone Adultes; Oncologie Medicale Et Usp
Marseille, France
ICM; Medecine B3
Montpellier, France
Gustave Roussy Cancer Campus
Villejuif, France
Universitätsklinikum Essen; Innere Klinik (Tumorforschung)
Essen, Germany
...and 34 more locations
Time frame: From first occurrence of documented CR or PR up to disease progression or study treatment discontinuation (assessed every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 38 months)
Progression-Free Survival (PFS) According to RECIST Version 1.1
PFS was defined as the time from study treatment initiation (Cycle 1 Day 1 \[1 cycle=14 days for QW/Q2W cohorts; 1 cycle=21 days for Q3W cohorts\]) to the first occurrence of documented disease progression (based on Investigator's assessment) or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
Time frame: Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months)
Overall Survival (OS)
OS was defined as the time from the first dose of study treatment to the time of death from any cause on study. Participants who were still alive at the time of analysis were censored at the last date known alive.
Time frame: From first dose of study treatment up to death due to any cause (up to approximately 47 months)
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be 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: Baseline up to end of the study (up to approximately 47 months)
Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods
Time frame: Baseline
Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods
Time frame: Baseline up 2 months
Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods
Time frame: Baseline up to 2 months
Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods
Time frame: Baseline up to 2 months