Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
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. |
Day 1 up to Day 28 of Cycle 1 |
|
| Primary |
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. |
From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy |
|
| Secondary |
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 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. |
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months) |
|
| Secondary |
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 NCI CTCAE version 5.0; where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and Grade 5=death. |
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment |
|
| Secondary |
Phase 1b of Sub-Study A: Number of Participants With Laboratory Abnormalities |
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. |
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months) |
|
| Secondary |
Phase 2 of Sub-Study A: Number of Participants With Laboratory Abnormalities |
Hematology and clinical chemistry parameters were planned to be assessed. |
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment |
|
| Secondary |
Phase 1b of Sub-Study A: Durable Objective Response Rate |
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. |
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) |
|
| Secondary |
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. |
From the date of first dose of study treatment until the date of the first documentation of PD (approximately 44 months) |
|
| Secondary |
Phase 2 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. |
From the date of first dose of study treatment until the date of the first documentation of PD |
|
| Secondary |
Phase 2 of Sub-Study A: 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. |
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 |
|
| Secondary |
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. |
From the date of first dose of study treatment to the date of first documentation of objective response |
|
| Secondary |
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. |
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 |
|
| Secondary |
Phase 2 of Sub-Study A: Overall Survival (OS) |
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. |
From the date of first dose of study treatment to the date of death due to any cause or censoring date |
|
| Secondary |
Phase 1b of Sub-Study A: Area Under the Concentration Verses Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab |
AUCtau was defined as area under the plasma concentration time curve from time zero to the next dose. |
Cycle 1 (pre-dose on Day 1, 168 hours [Day 8] and 336 hours [Day 15] and Day 28 post-dose) |
|
| Secondary |
Phase 2 of Sub-Study A: Area Under the Concentration Verses 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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
Phase 1b of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab |
|
Cycle 5 Day 1 (pre-dose) |
|
| Secondary |
Phase 2 of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab |
|
Cycle 5 Day 1 (pre-dose) |
|
| Secondary |
Phase 1b of Sub-Study A: Ctrough of Encorafenib |
|
Cycle 5 Day 1 (pre-dose) |
|
| Secondary |
Phase 2 of Sub-Study A: Ctrough of Encorafenib |
|
Cycle 5 Day 1 (pre-dose) |
|
| Secondary |
Phase 1b of Sub-Study A: Ctrough of Binimetinib |
|
Cycle 5 Day 1 (pre-dose) |
|
| Secondary |
Phase 2 of Sub-Study A: Ctrough of Binimetinib |
|
Cycle 5 Day 1 (pre-dose) |
|
| Secondary |
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). |
Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 255 days); each cycle is about 28 days |
|
| Secondary |
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; each cycle is about 28 days |
|
| Secondary |
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. |
From the date of first dose of study treatment until the date of the first documentation of PD |
|
| Secondary |
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. |
Baseline up to end of treatment |
|
| Secondary |
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. |
Baseline up to end of treatment |
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