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

Phase 1

Terminated

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: Sasanlimab Prefilled syringe
Drug: Sasanlimab
Drug: Encorafenib
Drug: Axitinib
Drug: SEA-TGT
Drug: Binimetinib

Registration Number: NCT04585815

Lead Sponsor: Pfizer

Brief Summary: Phase 1b/Phase 2 Umbrella Study; open-label, multi-center, parallel group study.

Sasanlimab (a PD-1 antagonist monoclonal antibody) will be combined with a different targeted therapy in each sub-study. Phase1b of each sub-study will evaluate the safety of the combination and select the dose for the Phase 2 portion. Phase 2 of each sub-study will evaluate the anti-tumor activity of the combination.

Sub-Study A is active, not recruiting, ongoing participants are still receiving treatment in Phase 1, Phase 2 will not be initiated.

Sub-study B is complete. All participants have discontinued treatment and any additional follow up required by protocol.

Detailed Description: Landscape 1011 is a clinical research study for people with advanced (stage 3b or 4) non-small cell lung cancer (NSCLC). The purpose of this study is to learn if the study medicine (sasanlimab, a type of immunotherapy) along with other study medicines is safe and effective in people with non-small cell lung cancer that has spread outside of the lungs. There are currently two sub-studies using different types of medicines. People in the first sub-study will receive sasanlimab as a subcutaneous (under the skin) injection at the study clinic every 4 weeks. Additionally, they will take targeted cancer therapies encorafenib by mouth once a day and binimetinib by mouth twice a day at home.

People in the second sub-study will receive the study medicine sasanlimab as a subcutaneous (under the skin) injection at the study clinic every 3 weeks and will also receive SEA-TGT (an immunotherapy) by infusion every three weeks.

Additionally, they will take axitinib (a targeted therapy) by mouth twice a day at home.

In addition to taking the study drugs, participants in the sub-studies will be asked to visit the clinic for health checks. These include health questions, physical examinations, blood and urine samples, and imaging scans. These assessments help the study doctor and team to monitor the participants' safety and well-being, and to see how their cancer is responding to the treatment. Participants will continue in the study until the cancer is no longer responding to the study medicine.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sub-Study A	Encorafenib	Sasanlimab will be administered subcutaneously. Encorafenib \& binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated.
Sub-Study A	Sasanlimab Prefilled syringe	Sasanlimab will be administered subcutaneously. Encorafenib \& binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated.
Sub-Study B	Sasanlimab	Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated.
Sub-Study B	SEA-TGT	Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated.
Sub-Study A	Binimetinib	Sasanlimab will be administered subcutaneously. Encorafenib \& binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated.
Sub-Study B	Axitinib	Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated.

Primary Outcome Measures

Name	Time	Method
Phase 2 Sub-Study B: Objective Response Rate	From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (maximum of 21 months)	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.
Phase 1b of Sub-Study A: Percentage of Participants With Dose-Limiting Toxicities (DLT)	Day 1 up to Day 28 of Cycle 1	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.
Phase 2 of Sub-Study A: Durable Objective Response Rate (ORR)	From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy	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.
Phase 1b of Sub-Study B: Percentage of Participants With DLT	Day 1 up to Day 21 of Cycle 1	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.

Secondary Outcome Measures

Name	Time	Method
Phase 1b of Sub-Study A: Number of Participants With Adverse Events (AEs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months)	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 will be 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.
Phase 2 of Sub-Study A: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment	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.
Phase 2 of Sub-Study A: Number of Participants With Laboratory Abnormalities	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment	Hematology and clinical chemistry parameters were planned to be assessed.
Phase 2 of Sub-Study B: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum of 21 months)	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
Phase 1b of Sub-Study A: Objective Response Rate	From the date of first dose of study treatment until the date of the first documentation of PD (approximately 44 months)	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.
Phase 1b of Sub-Study A: Number of Participants With Laboratory Abnormalities	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months)	Following assessments will be performed: hematology: hemoglobin, platelet count, white blood cell (WBC) count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils. Chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), bicarbonate or carbon dioxide (CO2), C-reactive protein (CRP), alkaline phosphatase, sodium, potassium, magnesium chloride, total calcium, total bilirubin, total protein, blood urea nitrogen (BUN) or urea, creatinine, creatinine clearance, uric acid, glucose (random), lactate dehydrogenase, albumin, phosphorus or phosphate, amylase, lipase.
Phase 2 of Sub-Study A: Progression-Free Survival (PFS)	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	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.
Phase 1b of Sub-Study A: Durable Objective Response Rate	From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (approximately 44 months)	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 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.
Phase 2 of Sub-Study A: Overall Survival (OS)	From the date of first dose of study treatment to the date of death due to any cause or censoring date	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.
Phase 1b of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab	Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 255 days) (1 cycle= 28 days)	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).
Phase 2 of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab	Pre-dose on Cycle 1 Day 1 until end of treatment
Phase 2 of Sub-Study A: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) Score	Baseline up to end of treatment	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.
Phase 2 of Sub-Study A: Objective Response Rate	From the date of first dose of study treatment until the date of the first documentation of PD	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.
Phase 2 of Sub-Study A: Duration of Response (DR)	From the date of first documentation of OR to the date of the first documentation of PD or death due to any cause, whichever occurred first	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.
Phase 1b of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab	Cycle 1 (pre-dose on Day 1, 168 hours [Day 8], 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 (pre-dose on Day 1 and 168 hours [Day 8] post dose) (1 cycle= 28 days)
Phase 2 of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab	Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days)
Phase 2 of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab	Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days)
Phase 1b of Sub-Study A: Ctrough of Binimetinib	Day 1 (pre-dose) of Cycles 1, 2, and 5 (1 cycle= 28 days)
Phase 2 of Sub-Study A: Objective Response (OR) Rate by Programmed Death Ligand-1 (PD-L1) Expression at Baseline	From the date of first dose of study treatment until the date of the first documentation of PD	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.
Phase 2 of Sub-Study B: Number of Participants With Shift From Baseline in Chemistry Parameter Values Based on CTCAE V5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum of 21 months)	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 shift from baseline in chemistry parameters by grades as per CTCAE version 5.0 were reported. Grade 0= any shift, Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Categories with at least 1 non-zero data values showing shift in Grade from baseline to post-baseline were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.
Phase 2 of Sub-Study A: Time to Tumor Response (TTR)	From the date of first dose of study treatment to the date of first documentation of objective response	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.
Phase 1b of Sub-Study A: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab	Cycle 1 (pre-dose on Day 1, 168 hours [Day 8] and 336 hours [Day 15] and Day 28 post-dose) (1 cycle= 28 days)	AUCtau was defined as area under the plasma concentration time curve from time zero to the next dose.
Phase 2 of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab	Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days)
Phase 2 of Sub-Study A: Ctrough of Encorafenib	Cycle 5 Day 1 (pre-dose)
Phase 1b of Sub-Study B: Number of Participants With Shift From Baseline in Chemistry Parameter Values Based on CTCAE V5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum of 21 months)	Chemistry parameters included: alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, chronic kidney disease, creatinine increased, hypercalcemia, hyperkalemia, hypoalbuminemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, lipase increased, serum amylase increased. Number of participants with shift from baseline in chemistry parameters by grades as per CTCAE version 5.0 were reported. Grade 0= any shift, Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Categories with at least 1 non-zero data values showing shift in Grade from baseline to post-baseline were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.
Phase 1b of Sub-Study B: Time to Tumor Response (TTR)	From the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) (maximum of 21 months)	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.
Phase 2 of Sub-Study B: Overall Survival (OS)	From the date of first dose of study treatment to the date of death due to any cause or censoring date, whichever occurred first (maximum of 21 months)	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.
Phase 2 of Sub-Study B: Cmax of Sasanlimab	Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days)
Phase 2 of Sub-Study B: Cmax of SEA-TGT	Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days)
Phase 2 of Sub-Study A: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab	Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) (1 cycle= 28 days)
Phase 1b of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab	Cycle 1 (pre-dose on Day 1, 168 hours [Day 8],336 hours [Day 15] and Day 28 post-dose) and Cycle 5 (pre-dose on Day 1 and 168 hours [Day 8] post dose) (1 cycle= 28 days)
Phase 1b of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab	Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days)
Phase 1b of Sub-Study A: Ctrough of Encorafenib	Day 1 (pre-dose) of Cycle 1, 2 and 5; Day 15 of Cycle 1 (1 cycle= 28 days)
Phase 2 of Sub-Study A: Ctrough of Binimetinib	Cycle 5 Day 1 (pre-dose)
Phase 1b of Sub-Study B: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum of 21 months)	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.
Phase 2 of Sub-Study B: Number of Participants With Shift From Baseline in Hematology Parameter Values Based on CTCAE V5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum of 21 months)	Hematology parameters included: anemia, hemoglobin increased, lymphocyte count decreased, 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= any shift, Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Categories with at least 1 non-zero data values showing shift in Grade from baseline to post-baseline were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.
Phase 2 of Sub-Study A: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score	Baseline up to end of treatment	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.
Phase 1b of Sub-Study B: Number of Participants With Shift From Baseline in Hematology Parameter Values Based on CTCAE V5.0	From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum of 21 months)	Hematology parameters included: anemia, lymphocyte count decreased, platelet count decreased, white blood cell decreased. Number of participants with shift from baseline in hematology parameters by grades (as per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) were reported. Grade 0= any shift, Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Categories with at least 1 non-zero data values showing shift in Grade from baseline to post-baseline were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.
Phase 2 of Sub-Study B: Time to Tumor Response (TTR)	From the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) (maximum of 21 months)	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.
Phase 1b of Sub-Study B: Cmax of Sasanlimab	Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days)
Phase 2 of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of SEA-TGT	Pre-dose on Cycle 1 Day 1; pre-dose on Cycle 5 Day 1 (1 cycle= 21 days)
Phase 1b of Sub-Study B: Cmax of SEA-TGT	Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days)
Phase 1b of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Axitinib	Pre-dose on Cycle 1 Day 1 and Day 8; pre-dose on Cycle 5 Day 1 and Day 8 (1 cycle= 21 days)
Phase 2 of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab	Cycle 1: pre-dose on Day 1, Cycle 5: pre-dose on Day 1 (1 cycle= 21 days)
Phase 1b of Sub-Study B: Objective Response Rate (ORR)	From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy, whichever occurred first (maximum of 21 months)	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.
Phase 2 of Sub-Study B: Duration of Response (DR)	From date of first documentation of OR to the date of first documentation of PD or death, whichever occurred first (maximum of 21 months)	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.
Phase 2 of Sub-Study B: Progression-Free Survival (PFS)	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 (maximum of 21 months)	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.
Phase 1b of Sub-Study B: Cmax of Axitinib	Cycle 1: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1; Cycle 5: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1 (1 cycle= 21 days)
Phase 1b of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab	Pre-dose on Cycle 1 Day 1 and Cycle 5 Day 1 (1 cycle= 21 days)
Phase 1b of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of SEA-TGT	Pre-dose on Cycle 1 Day 1; pre-dose on Cycle 5 Day 1 (1 cycle= 21 days)
Phase 2 of Sub-Study B: Number of Participants With Positive Anti-Drug Antibody (ADA) Against Sasanlimab and SEA-TGT	Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 21 months) (1 cycle= 21 days)
Phase 1b of Sub-Study B: Duration of Response (DR)	From the date of first documentation of OR to the date of first documentation of PD or death, whichever occurred first (maximum of 21 months)	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.
Phase 1b of Sub-Study B: Progression-Free Survival (PFS)	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 (maximum of 21 months)	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.
Phase 2 of Sub-Study B: Cmax of Axitinib	Cycle 1: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1; Cycle 5: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1 (1 cycle= 21 days)
Phase 2 of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Axitinib	Pre-dose on Cycle 1 Day 1 and Day 8; pre-dose on Cycle 5 Day 1 and Day 8 (1 cycle= 21 days)
Phase 1b of Sub-Study B: Number of Participants With Positive Anti-Drug Antibody (ADA) Against Sasanlimab and SEA-TGT	Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 21 months) (1 cycle= 21 days)	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).
Phase 2 of Sub-Study B: Objective Response Rate by PD-L1 Expression in Available Tumor Tissue	From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (maximum of 21 months)	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.

Trial Locations

Locations (53): Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳
Taipei, Taiwan
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
UCHealth Memorial Hospital North
🇺🇸
Colorado Springs, Colorado, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
Austin Health
🇦🇺
Heidelberg, Victoria, Australia
City of Hope
🇺🇸
Duarte, California, United States
Sulpizio Cardiovascular Center at UC San Diego Health
🇺🇸
La Jolla, California, United States
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
🇺🇸
La Jolla, California, United States
UCSD Perlman Medical Offices
🇺🇸
La Jolla, California, United States
Henry Ford Medical Center - Fairlane
🇺🇸
Dearborn, Michigan, United States
UCSD Medical Center - Encinitas
🇺🇸
Encinitas, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸
Whittier, California, United States
AdventHealth Celebration Infusion Center
🇺🇸
Celebration, Florida, United States
North Shore Radiology and Nuclear Medicine
🇦🇺
St Leonards, New South Wales, Australia
UZ Gent
🇧🇪
Gent, Belgium
Koo Foundation Sun Yat -Sen Cancer Center
🇨🇳
Taipei City, Taiwan
Royal Victoria Infirmary
🇬🇧
Newcastle upon Tyne, United Kingdom
Concord Hospital
🇦🇺
Concord, New South Wales, Australia
Tennessee Oncology PLLC
🇺🇸
Smyrna, Tennessee, United States
Antwerp University Hospital
🇧🇪
Edegem, Antwerpen, Belgium
Mount Sinai Hospital Pharmacy
🇺🇸
New York, New York, United States
AdventHealth Orlando
🇺🇸
Orlando, Florida, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
UZ Leuven
🇧🇪
Leuven, Belgium
Chung Shan Medical University Hospital
🇨🇳
Taichung, Taiwan
Sir Bobby Robson Cancer Trials Research Centre
🇬🇧
Newcastle upon Tyne, United Kingdom
UC San Diego Medical Center - Hillcrest
🇺🇸
San Diego, California, United States
California Cancer Associates for Research and Excellence, Inc (cCARE)
🇺🇸
Fresno, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Florida Cancer Specialists
🇺🇸
Winter Park, Florida, United States
University of Maryland Medical Center -IDS Pharmacy
🇺🇸
Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Chris O'Brien Lifehouse
🇦🇺
Camperdown, New South Wales, Australia
Henry Ford Medical Center - Columbus
🇺🇸
Novi, Michigan, United States
Sarah Cannon Research Institute - Pharmacy
🇺🇸
Nashville, Tennessee, United States
AdventHealth Medical Group Oncology Research at Celebration
🇺🇸
Celebration, Florida, United States
Ophthalmic Consultants of Boston Inc (OCB)
🇺🇸
Boston, Massachusetts, United States
GenesisCare North Shore
🇦🇺
St Leonards, New South Wales, Australia
City of Hope Investigational Drug Services (IDS)
🇺🇸
Duarte, California, United States
Koman Family Outpatient Pavilion
🇺🇸
La Jolla, California, United States
UC San Diego Moores Cancer Center - Investigational Drug Services
🇺🇸
La Jolla, California, United States
UCSD Medical Center - Vista
🇺🇸
Vista, California, United States
UCHealth Memorial Hospital Central
🇺🇸
Colorado Springs, Colorado, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Advent Health Orlando - Investigational Drug Services
🇺🇸
Orlando, Florida, United States
AdventHealth Orlando Infusion Center
🇺🇸
Orlando, Florida, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
University of Maryland Greenebaum Comprehensive Cancer Center
🇺🇸
Baltimore, Maryland, United States
Atlantic Health System / Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Medical Diagnostic Associates
🇺🇸
Summit, New Jersey, United States
Overlook Medical Center
🇺🇸
Summit, New Jersey, United States
Sarah Cannon Research Institute UK
🇬🇧
London, United Kingdom