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

Phase 2TerminatedNCT04585815

Pfizer34 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria Umbrella Phase 1b \& 2: * Histologically or cytologically confirmed locally advanced/metastatic (Stage IIIB-IV) NSCLC. * At least one measurable lesion per RECIST v1.1 at Screening. * ECOG Performance Status 0 or 1. * Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1. * Adequate hepatic, renal, and bone marrow function. Additional Inclusion Criteria for Sub-Study A Phase 1b \&2: -BRAFV600E mutation in tumor tissue or plasma as determined by a local laboratory PCR or NGS assay and documented in a local pathology report. Additional Inclusion Criteria for Sub-Study A Phase 1b only: -Any line of therapy for locally advanced/metastatic NSCLC. Additional Inclusion Criteria for Sub-Study A Phase 2 only: -Previously untreated for locally advanced/metastatic NSCLC Additional Inclusion Criteria for Sub-Study B Phase 1b only:: -Any line of therapy for locally advanced/metastatic NSCLC. Additional Inclusion Criteria for Sub-Study B Phase 2 only: * Previously untreated for locally advanced/metastatic NSCLC (Arms B1 \& B2), or * One or 2 prior lines of therapy for advanced/metastatic NSCLC (Arm B3), including immune checkpoint inhibitor treatment + chemotherapy, and have progressed during or after that therapy. * PD-L1 TPS ≥1% Exclusion Criteria Umbrella Phase 1b \&2: * Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. * Active non-infectious pneumonitis, pulmonary fibrosis, or known history of immune-mediated pneumonitis. * Active infection requiring systemic therapy. * Clinically significant cardiovascular disease. * Other malignancy within 2 years of first dose, with exceptions. * Symptomatic brain metastasis, with exceptions. Additional Exclusion Criteria for Sub-Study A Phase 1b\&2: * EGFR mutation, ALK fusion oncogene, or ROS1 rearrangement. * Prior treatment with any BRAF inhibitor or MEK inhibitor. Additional Exclusion Criteria for Sub-Study A Phase 2 only: -Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents. Additional Exclusion Criteria for Sub-Study B Phase 1b\&2: -Documentation of any tumor-driving molecular alteration (eg, BRAF, EGFR, ALK) Additional Exclusion Criteria for Sub-Study B Phase 2 only: * Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.(Arms B1 \& B2) * Confirmed progressive disease on 1st or 2nd imaging tumor assessment after initiation of therapy for advanced/metastatic NSCLC.

Locations (55)

City of Hope Investigational Drug Services (IDS)

Duarte, California, United States

City of Hope

Duarte, California, United States

UCSD Medical Center - Encinitas

Encinitas, California, United States

California Cancer Associates for Research and Excellence, Inc (cCARE)

Fresno, California, United States

The Oncology Institute of Hope and Innovation

Glendale, California, United States

Outcomes

Primary Outcomes

Phase 1b of Sub-Study A: Percentage of Participants With Dose-Limiting Toxicities (DLT)

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.

Time frame: Day 1 up to Day 28 of Cycle 1

Phase 2 of Sub-Study A: Durable Objective Response Rate (ORR)

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.

Time frame: From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy

Phase 1b of Sub-Study B: Percentage of Participants With DLT

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.

Time frame: Day 1 up to Day 21 of Cycle 1

Phase 2 Sub-Study B: Objective Response Rate

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.

Time frame: 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)

Secondary Outcomes

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

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months)

Phase 2 of Sub-Study A: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment

Phase 1b of Sub-Study A: Number of Participants With Shift From Baseline in Hematology Parameters Values Based on CTCAE V5.0

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months)

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.

Phase 1b of Sub-Study A: Durable Objective Response Rate (ORR)

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.

Time frame: 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 38.66 months)

Phase 1b of Sub-Study A: Objective Response Rate

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.

Time frame: 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 38.66 months)

Phase 2 of Sub-Study A: Objective Response Rate

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.

Time frame: From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy

Phase 2 of Sub-Study A: Duration of Response (DR)

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.

Time frame: 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

Phase 2 of Sub-Study A: Time to Tumor Response (TTR)

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.

Time frame: From the date of first dose of study treatment to the date of first documentation of objective response

Phase 2 of Sub-Study A: Progression-Free Survival (PFS)

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.

Time frame: 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

Phase 1b of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab

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).

Time frame: Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 255 days) (1 cycle= 28 days)

Phase 2 of Sub-Study A: Objective Response (OR) Rate by Programmed Death Ligand-1 (PD-L1) Expression at Baseline

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.

Time frame: From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy

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

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.

Time frame: Baseline up to 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-Lung Cancer 13 (QLQ- LC13) Score

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.

Time frame: Baseline up to end of treatment

Phase 1b of Sub-Study B: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months)

Phase 2 of Sub-Study B: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0

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

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months)

Phase 1b of Sub-Study B: Number of Participants With Shift From Baseline in Hematology Parameters Values Based on CTCAE V5.0

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 39.3 months; maximum follow-up approximately 39.66 months)

Phase 1b of Sub-Study B: Number of Participants With Shift From Baseline in Chemistry Parameters Values Based on CTCAE V5.0

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months)

Phase 2 of Sub-Study B: Number of Participants With Shift From Baseline in Hematology Parameter Values Based on CTCAE V5.0

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months)

Phase 2 of Sub-Study B: Number of Participants With Shift From Baseline in Chemistry Parameter Values Based on CTCAE V5.0

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.

Time frame: From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months)

Phase 1b of Sub-Study B: Objective Response Rate

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.

Time frame: 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)

Phase 1b of Sub-Study B: Duration of Response (DR)

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.

Time frame: 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)

Phase 1b of Sub-Study B: Time to Tumor Response (TTR)

Time frame: 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)

Phase 1b of Sub-Study B: Progression-Free Survival (PFS)

Time frame: 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)

Phase 2 of Sub-Study B: Duration of Response (DR)

Time frame: From date of first documentation of OR to the date of first documentation of PD or death, whichever occurred first (maximum of 21 months)

Phase 2 of Sub-Study B: Time to Tumor Response (TTR)

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.

Time frame: 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)

Phase 2 of Sub-Study B: Progression-Free Survival (PFS)

Time frame: 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)

Phase 1b of Sub-Study B: Number of Participants With Positive Anti-Drug Antibody (ADA) Against Sasanlimab and SEA-TGT

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).

Time frame: Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 21 months) (1 cycle= 21 days)

Phase 2 of Sub-Study B: Objective Response Rate by PD-L1 Expression in Available Tumor Tissue

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.

Time frame: 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)

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

Overview

Conditions

Interventions

Eligibility

Locations (55)

Outcomes

Primary Outcomes

Secondary Outcomes