Trial Outcomes & Findings for Study of Immunotherapy (Sasanlimab) in Combination With Targeted Therapies in People With Advanced Non-small Cell Lung Cancer (NSCLC) (Landscape 1011 Study) (NCT NCT04585815)

Sub-study A (SSA) was planned to be conducted in 2 parts: Phase 1b and Phase 2. Due to a business decision, Phase 2 was not initiated, hence no participants were enrolled for Phase 2 of SSA. Sub-study B (SSB) was conducted in 2 parts: Phase 1b and Phase 2.

57 participants signed informed consent and 34 participants were enrolled in the study. Of these 34 participants, 13 were enrolled in Sub-study A and 21 in Sub-study B (9 in Phase \[Ph\] 1b and 12 in Phase 2).

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

DLT=AEs in DLT observation period (OP) related to any study intervention:Grade (G)4 neutropenia;thrombocytopenia or anemia;febrile neutropenia;neutropenic infection;G3 thrombocytopenia with bleeding. Any G\>=3 toxicity (except transient G3 fatigue, local reactions/headache that resolved to G\<=1/baseline; G3 nausea, vomiting controlled within 72 hrs, G3 hypertension controlled by medical therapy (MT), G3 diarrhea that improved to G\<=2 within 72 hrs, G3 skin toxicity that resolved to G\<=1 in \<7 days after MT, G3 endocrinopathies controlled by MT and tumors flare); Non-hematologic G3 lab abnormality \[LA\](medical intervention or hospitalization), or any G4 LA;ALT/AST\>3\*ULN (normal at baseline) or \>3\*ULN and doubling baseline (\>ULN at baseline) and associated with total bilirubin(TB) \>2\*ULN;or ALT/AST\>5\*ULN; or TB\>3\*ULN. Missing 75% of planned doses during DLT OP due to treatment-related toxicities. AE not listed/DLT criteria outside DLT OP was DLT at discretion of sponsor and investigator.

Durable ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 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 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.

DLT=AEs in DLT OP related to any study intervention: G4 neutropenia; thrombocytopenia or anemia; neutropenia; neutropenic infection; G3 thrombocytopenia with bleeding. Any G\>=3 toxicity (except transient G3 fatigue, local reactions/headache that resolved to G\<=1/baseline; G3 nausea, vomiting controlled within 72 hrs, G3 hypertension controlled by MT, G3 diarrhea that improved to G\<=2 within 72 hrs, G3 skin toxicity that resolved to G\<=1 in \<7 days after MT, G3 endocrinopathies controlled by MT and tumors flare); Non-hematologic G3 LA (medical intervention or hospitalization), or any G4 LA;ALT/AST\>3\*ULN (normal at baseline) or \>3\*ULN and doubling baseline (\>ULN at baseline) and associated with TB \>2\*ULN; or ALT/AST\>5\*ULN; or TB\>3\*ULN. Missing 75% of planned doses during DLT OP due to treatment-related toxicities. AE not listed/DLT criteria outside DLT OP was DLT at discretion of sponsor and investigator.

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 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.

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.