Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Pembrolizumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy, followed by pembrolizumab 200 mg every 3 weeks.

Letetresgene autoleucel (GSK3377794) as an IV infusion

Letetresgene autoleucel

Letetresgene autoleucel (GSK3377794) as an IV infusion, followed by pembrolizumab every 3 weeks

Letetresgene autoleucel with pembrolizumab

Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Pembrolizumab is available as an IV infusion

GSK Clinical Trials

This trial will evaluate safety, tolerability, and efficacy of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with relapsed and refractory multiple myeloma.

Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma

Open-Label Pilot Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered NY-ESO-1 Specific (c259) T Cells Alone or in Combination With Pembrolizumab in HLA-A2+ Subjects With NY-ESO-1 and/or LAGE-1a Positive Relapsed and Refractory Multiple Myeloma

IPD for this study will be made available via the Clinical Study Data Request site.

An AE is any untoward medical occurrence in a participant or clinical investigation participant who received a study treatment and the event need not necessarily have a causal relationship with study treatment. An SAE is any AE that results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in a persistent or significant disability; is a congenital anomaly/birth defect; is clinically significant or requires intervention to prevent one of the outcomes listed before.

The following toxicities were considered to be treatment limiting toxicities: any \>=Grade 4 AE; Grade 3 non-infectious pneumonitis and any other Grade 3 AE (excluding pneumonitis), that did not improve to Grade 2 within 7 days after onset despite medical management and supportive care. Exceptions included the following: Grade 3 or 4 leukopenia, lymphopenia, neutropenia, or febrile neutropenia; Grade 3 or 4 thrombocytopenia not associated with significant bleeding; Grade 3 anemia; Grade 4 cytokine release syndrome (CRS) or toxicities related to CRS that resolved to Grade \<=2 within 7 days; other Grade 3 laboratory abnormality determined to be not clinically significant by the Investigator; Grade 3 or 4 fever and chills; Grade 3 or 4 hypoalbuminemia or abnormal electrolytes that responded to supplementation/correction; AE related to the cancer or its progression.

Blood samples were collected for the assessment of following clinical chemistry parameters: glucose, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, potassium, magnesium, phosphate, sodium and calcium. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case post Baseline is presented.

Blood samples were collected for the assessment of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Laboratory parameters were graded according to NCI-CTCAE version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case post Baseline is presented.

Blood samples were collected for the assessment of following coagulation parameters: prothrombin time and partial thromboplastin time (PTT). A laboratory value that is outside the normal range is considered either high abnormal (value above the upper limit of the normal range) or low abnormal (value below the lower limit of the normal range). Participants were counted twice if the participant had values in 'Decreased to low' and 'Increased to high' during the post-Baseline period. Data for worst case post Baseline is presented.

ECG was recorded using an ECG machine that automatically calculated the heart rate and measured PR, RR, QRS and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal clinically significant ECG findings for worst case post-Baseline has been presented. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Overall response rate is defined as the percentage of participants with a best overall response (BOR) of confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) Response Criteria (2016); where, PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 milligrams (mg) per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or sCR: CR as defined by normal free light chain (FLC) ratio and absence of clonal cells by immunohistochemistry. Confidence intervals were calculated using the exact (Clopper-Pearson) method.

Time to response is defined as the time interval (in months) from T-cell infusion to initial date of documented confirmed response (PR or better) in the subset of participants who showed a confirmed BOR of PR or better by Investigator assessment per IMWG (2016).

Duration of response is defined as the interval between the initial date of the confirmed response (sCR, CR, VGPR, or PR) and the initial assesment date of confirmed progressive disease or death among participants with a confirmed response per IMWG (2016).

Progression Free Survival is defined as the interval between the date of T-cell infusion and the initial assessment date of confirmed progressive disease as assessed by the investigator per IMWG (2016) or date of death. Progressive disease is defined as an increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>=0.5 grams per deciliter (g/dL); Serum M-protein increase \>=1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>=200 mg per 24 hours).

Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in deoxyribonucleic acid (DNA) extracted from peripheral blood mononuclear cell (PBMC).

Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in DNA extracted from PBMC.

Merck Sharp & Dohme LLC

GlaxoSmithKline

Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.

Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.

GSK3377794

Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.

GSK3377794+Pembrolizumab

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

GSK Response Center

Any AE

Any SAE

Intent-To-Treat (ITT) Population comprised of all participants who underwent leukapheresis

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

ITT Population. Treatment limiting toxicities were assessed in GSK3377794+pembrolizumab arm only.

Number of Participants With Treatment Limiting Toxicities-GSK3377794+Pembrolizumab Arm Only

Glucose (Hyperglycemia)

Glucose (Hypoglycemia)

Albumin (Hypoalbuminemia)

ALP increased

ALT increased

AST increased

Bilirubin increased

Creatinine increased

Potassium (Hyperkalemia)

Potassium (Hypokalemia)

Magnesium (Hypermagnesemia)

Magnesium (Hypomagnesemia)

Phosphate (Hypophosphatemia)

Sodium (Hypernatremia)

Sodium (Hyponatremia)

Calcium (Hypercalcemia)

Calcium (Hypocalcemia)

Modified ITT Population comprised of all participants in the ITT Population who received the NY-ESO-1c259T infusion.

Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline

Hemoglobin (Anemia)

Hemoglobin increased

Lymphocyte count decreased

Lymphocyte count increased

Neutrophil count decreased

Platelet count decreased

Leukocyte count decreased

Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline

Prothrombin Time; decrease to low

Prothrombin Time; To normal or no change

Prothrombin Time; increase to high

PTT; decrease to low

PTT; To normal or no change

PTT; increase to high

Modified ITT Population. Only those participants with data available at the specified time point is reported

Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline

Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings

Overall Response Rate

Modified ITT Population. Only those participants with a confirmed response per IMWG 2016 were analyzed.

Spots Global Cancer Trial Database for Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial