The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Sasanlimab is an investigational compound. Its safety and efficacy have not been established.
Active Not-enrolling
United States, Australia, Belgium, Taiwan, United Kingdom
for more information at clinicaltrials.gov
EXPERIMENTAL: Sub-Study A
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.
DRUG: Sasanlimab Prefilled syringe
prefilled syringe
DRUG: Encorafenib
capsules
DRUG: Binimetinib
tablets
EXPERIMENTAL: Sub-Study B
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.
DRUG: Sasanlimab
solution supplied in vials
DRUG: Axitinib
tablets
DRUG: SEA-TGT
solution in vials
Inclusion Criteria Umbrella Phase 1b & 2:
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:
Exclusion Criteria Umbrella Phase 1b \&2:
Additional Exclusion Criteria for Sub-Study A Phase 1b\&2:
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:
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\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
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 \
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 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)
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
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)
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
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 \
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)
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 \
From the date of first dose of study treatment until the date of the first documentation of PD (approximately 44 months)
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 \
From the date of first dose of study treatment until the date of the first documentation of PD
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 \
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 \
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.
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 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
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)
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)
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)
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)
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)
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)
Phase 1b of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab
Cycle 5 Day 1 (pre-dose)
Phase 2 of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab
Cycle 5 Day 1 (pre-dose)
Phase 1b of Sub-Study A: Ctrough of Encorafenib
Cycle 5 Day 1 (pre-dose)
Phase 2 of Sub-Study A: Ctrough of Encorafenib
Cycle 5 Day 1 (pre-dose)
Phase 1b of Sub-Study A: Ctrough of Binimetinib
Cycle 5 Day 1 (pre-dose)
Phase 2 of Sub-Study A: Ctrough of Binimetinib
Cycle 5 Day 1 (pre-dose)
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
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
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 \
From the date of first dose of study treatment until the date of the first documentation of PD
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
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
34
Sponsor: Pfizer
Collaborator: None
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT04585815
Back
