Study of Immunotherapy (Sasanlimab) in Combination With Targeted Therapies in People With Advanced Non-small Cell Lung Cancer (NSCLC) (Landscape 1011 Study)

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs was graded by the investigator according to NCI CTCAE grade 1 to 5 version 5.0; where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and Grade 5=death.

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were planned to be graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0; where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and Grade 5=death.

Hematology parameters included: anemia, hemoglobin increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, leukocytosis, neutrophil count decreased, platelet count decreased, white blood cell decreased. Laboratory abnormalities were graded as per NCI- CTCAE v 5.0 where, grade(G) 0= non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe and G4= life-threatening or disabling. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants with shift from baseline in hematology parameters by grades (as per CTCAE version 5.0) were reported.

Chemistry parameters included: alanine aminotransferase (ALT) increase, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatinine phosphokinase (CPK) increased, chronic kidney disease (CKD), creatinine increased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, lipase increased, serum amylase increased. Chemistry abnormalities were graded as per NCI- CTCAE v 5.0 where, grade(G) 0= non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe and G4= life-threatening or disabling. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants with shift from baseline in hematology parameters by grades (as per CTCAE version 5.0) were reported.

Hematology and clinical chemistry parameters were planned to be assessed.

Durable ORR was defined as percentage of participants with confirmed CR or PR according to RECIST v1.1 based on investigator assessment, lasting for at least 10 months from the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy. CR was defined as complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 milli meter [mm]). PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. Non-CR/Non-PD: Persistence of any non-target lesions and/or tumor marker level (if being followed) above the normal limits.

Objective response rate is defined as percentage of participants with confirmed best overall response of CR or PR according to RECIST v1.1 from the date of first dose of study treatment until the date of the first documentation of PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. Non-CR/Non-PD: Persistence of any non-target lesions and/or tumor marker level (if being followed) above the normal limits.

Objective response (OR) rate is defined as percentage of participants with confirmed best overall response of CR or PR according to RECIST v1.1 from the date of first dose of study treatment until the date of the first documentation of PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.

DR was defined for participants with confirmed OR as time from date of first documentation of OR to the date of first documentation of PD or death (any cause), whichever occurred first. OR=CR or PR according to RECIST v1.1 based on investigator assessment. CR and PR must be confirmed by repeat assessments performed no <4 weeks after criteria for response were first met. CR=complete disappearance of all target lesions (TLs) with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR=greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions (TMLs). PD=20% increase in sum of diameters of TMLs above smallest sum observed (over baseline if no decrease in sum was observed during therapy), with a minimum absolute increase of 5 mm.

TTR is defined for participants with confirmed objective response as the time from the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) which was subsequently confirmed. CR=complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR=greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.

PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of PD or death due to any cause, whichever occurred first. PD=20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in sum was observed during therapy), with a minimum absolute increase of 5 mm.

OS is defined as the time from the date of first dose of study treatment to the date of death due to any cause. Participants last known to be alive were planned to be censored at the date of last contact.

AUCtau was defined as area under the plasma concentration time curve from time zero to the next dose.

In this outcome measure, number of ADA-positive and NAb-positive participants has been presented. A participant was considered ADA (or NAb) positive if (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a >= [4-fold dilution increase] in titer (equivalent to 0.602 unit increase in logarithm to base 10 (log10) titer from baseline in >= 1 post-treatment sample (treatment-boosted).

OR rate is defined as percentage of participants with CR or PR according to RECIST v1.1 based on investigator assessment. CR=complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR=greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. OR by PD-L1 expression at baseline was planned to be assessed.

EORTC QLQ-C30: consisted of 30 questions grouped into 5 functional scales (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale; 3 symptom scales (fatigue, pain, nausea and vomiting); and 6 single items that assessed additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea), and financial impact. All scales and single item measures ranged in score from 0 to 100. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on the functional scales represent higher levels of functioning. Higher scores on the symptom scales and single items represent a greater presence of symptoms or financial impact.

The EORTC QLQ-LC13 is the lung cancer specific module of the EORTC Quality of Life Questionnaire. The EORTC QLQ-LC13 consisted of 13 questions which included 1 multi-item scale and 9 single items assessing symptoms (dyspnea, cough, hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication use. The item scale ranged from 1 to 4 (1 = Not at all; 4 = Very Much) where the EORTC-QLQ-LC13 scoring algorithm was applied to convert to a 0 to 100 point scale where 100 is best quality of life (QOL), for comparability. Higher scores are reflective of a greater presence of symptoms.

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were graded by the investigator according to NCI CTCAE version 5.0; where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and Grade 5=death.

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were graded by the investigator according to NCI CTCAE version 5.0; where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and Grade 5=death

Hematology parameters included: anemia, hemoglobin increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased. Laboratory abnormalities were graded as per NCI- CTCAE v 5.0 where, grade(G) 0= non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe and G4= life-threatening or disabling. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants with shift from baseline in hematology parameters by grades (as per CTCAE version 5.0) were reported.

Chemistry parameters included: alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatinine phosphokinase (CPK) increased, chronic kidney disease (CKD), creatinine increased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, lipase increased, serum amylase increased. Chemistry abnormalities were graded as per NCI- CTCAE v 5.0 where, grade(G) 0= non-missing lab value that does not meet either of G1 through 4 criteria, G1=mild, G2=moderate, G3=severe and G4= life-threatening or disabling. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants with shift from baseline in hematology parameters by grades (as per CTCAE version 5.0) were reported.

Hematology parameters included: anemia, hemoglobin increased, lymphocyte count decreased, leukocytosis, neutrophil count decreased, platelet count decreased, white blood cell decreased. Number of participants with shift from baseline in hematology parameters by grades as per CTCAE version 5.0 were reported. Grade 0= non-missing lab value that does not meet either of Grade 1 through 4 criteria; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

Chemistry parameters included: ALT increased, ALP increased, AST increased, blood bilirubin increased, chronic kidney disease, creatinine increased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, lipase increased, serum amylase increased. Number of participants with maximum CTCAE V5.0 grade in chemistry parameters were reported. Grade 0= non-missing lab value that does not meet either of Grade 1 through 4 criteria; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

ORR was defined as percentage of participants with confirmed CR or PR according to RECIST v1.1 based on investigator assessment, from the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy. CR was defined as complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. Two sided 95% CI was based on Clopper-Pearson method.

DR was defined for participants with confirmed objective response (OR) as time from date of first documentation of OR to the date of first documentation of PD or death (any cause), whichever occurred first. OR=CR or PR according to RECIST v1.1 based on investigator assessment. CR and PR must be confirmed by repeat assessments performed no <4 weeks after criteria for response were first met. CR=complete disappearance of all target lesions (TLs) with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR=greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions (TMLs). PD=20% increase in sum of diameters of TMLs above smallest sum observed (over baseline if no decrease in sum was observed during therapy), with a minimum absolute increase of 5 mm.

TTR is defined for participants with confirmed objective response as the time from the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) which was subsequently confirmed. CR=complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR=greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.

PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of PD or death due to any cause, whichever occurred first. PD=20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in sum was observed during therapy), with a minimum absolute increase of 5 mm.

DR was defined for participants with confirmed OR as time from date of first documentation of OR to the date of first documentation of PD or death (any cause), whichever occurred first. OR=CR or PR according to RECIST v1.1 based on investigator assessment. CR and PR must be confirmed by repeat assessments performed no <4 weeks after criteria for response were first met. CR=complete disappearance of all target lesions (TLs) with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR=greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions (TMLs). PD=20% increase in sum of diameters of TMLs above smallest sum observed (over baseline if no decrease in sum was observed during therapy), with a minimum absolute increase of 5 mm.

TTR is defined for participants with confirmed OR as the time from the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) which was subsequently confirmed. CR=complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR=greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.

PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of PD or death due to any cause, whichever occurred first. PD=20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in sum was observed during therapy), with a minimum absolute increase of 5 mm.

OS is defined as the time from the date of first dose of study treatment to the date of death due to any cause. Participants last known to be alive were planned to be censored at the date of last contact.

A participant was considered ADA (or NAb) positive if (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a >= [4-fold dilution increase] in titer (equivalent to 0.602 unit increase in logarithm to base 10 (log10) titer from baseline in >= 1 post-treatment sample (treatment-boosted).

ORR was defined as percentage of participants with confirmed CR or PR according to RECIST v1.1 based on investigator assessment, from the date of first CR or PR until the date of the first documentation of disease progression (PD), death, or start of new anticancer therapy. CR was defined as complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10 millimeter [mm]). PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm.