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NCT03168438

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

Terminated Phase 1 Results posted Last updated 11 January 2022
What this trial tests

Phase 1 trial testing Letetresgene autoleucel in Neoplasms in 6 participants. Terminated before completion.

Timeline
18 August 2017
Primary endpoint
13 July 2020
5 November 2020

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment6
Start date18 August 2017
Primary completion13 July 2020
Estimated completion5 November 2020
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · Up to 108 weeks

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.

Any AE
GroupValue95% CI
GSK33777943
GSK3377794+Pembrolizumab3
Any SAE
GroupValue95% CI
GSK33777942
GSK3377794+Pembrolizumab2
Number of Participants With Treatment Limiting Toxicities-GSK3377794+Pembrolizumab Arm Only Primary · Up to 3 weeks

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; ot

GroupValue95% CI
GSK3377794+Pembrolizumab0
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Primary · Up to 108 weeks

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

Glucose (Hyperglycemia)
GroupValue95% CI
GSK33777942
GSK3377794+Pembrolizumab2
Glucose (Hypoglycemia)
GroupValue95% CI
GSK33777940
GSK3377794+Pembrolizumab0
Albumin (Hypoalbuminemia)
GroupValue95% CI
GSK33777943
GSK3377794+Pembrolizumab2
ALP increased
GroupValue95% CI
GSK33777941
GSK3377794+Pembrolizumab1
ALT increased
GroupValue95% CI
GSK33777940
GSK3377794+Pembrolizumab1
AST increased
GroupValue95% CI
GSK33777940
GSK3377794+Pembrolizumab1
Bilirubin increased
GroupValue95% CI
GSK33777940
GSK3377794+Pembrolizumab1
Creatinine increased
GroupValue95% CI
GSK33777941
GSK3377794+Pembrolizumab3
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Primary · Up to 108 weeks

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.

Hemoglobin (Anemia)
GroupValue95% CI
GSK33777942
GSK3377794+Pembrolizumab3
Hemoglobin increased
GroupValue95% CI
GSK33777940
GSK3377794+Pembrolizumab0
Lymphocyte count decreased
GroupValue95% CI
GSK33777943
GSK3377794+Pembrolizumab3
Lymphocyte count increased
GroupValue95% CI
GSK33777940
GSK3377794+Pembrolizumab0
Neutrophil count decreased
GroupValue95% CI
GSK33777943
GSK3377794+Pembrolizumab3
Platelet count decreased
GroupValue95% CI
GSK33777943
GSK3377794+Pembrolizumab3
Leukocyte count decreased
GroupValue95% CI
GSK33777943
GSK3377794+Pembrolizumab3
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline Primary · Up to 108 weeks

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.

Prothrombin Time; decrease to low
GroupValue95% CI
GSK33777940
Prothrombin Time; To normal or no change
GroupValue95% CI
GSK33777940
Prothrombin Time; increase to high
GroupValue95% CI
GSK33777941
PTT; decrease to low
GroupValue95% CI
GSK33777940
PTT; To normal or no change
GroupValue95% CI
GSK33777941
PTT; increase to high
GroupValue95% CI
GSK33777940
Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Primary · Up to 108 weeks

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.

GroupValue95% CI
GSK33777940
GSK3377794+Pembrolizumab1
Overall Response Rate Secondary · Up to 108 weeks

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-pro

GroupValue95% CI
GSK337779433.30.8 – 90.6
GSK3377794+Pembrolizumab66.79.4 – 99.2
Time to Response Secondary · Up to 108 weeks

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).

GroupValue95% CI
GSK33777940.7NA – NA
GSK3377794+Pembrolizumab0.70.7 – 0.7
Duration of Response Secondary · Up to 108 weeks

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).

GroupValue95% CI
GSK33777942.1NA – NA
GSK3377794+Pembrolizumab2.12.1 – 2.1
Progression-free Survival Secondary · Up to 108 weeks

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).

GroupValue95% CI
GSK33777942.791.31 – 5.16
GSK3377794+Pembrolizumab2.782.76 – 2.79
Maximum Persistence (Cmax) of GSK3377794 Secondary · Up to 108 weeks

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).

GroupValue95% CI
GSK337779438509.67± 160.5
GSK3377794+Pembrolizumab89640.56± 84.8
Time to Maximum Persistence Secondary · Up to 108 weeks

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

GroupValue95% CI
GSK33777948.05 – 15
GSK3377794+Pembrolizumab8.07 – 15

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious AEs and SAEs were collected up to 108 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK3377794
Serious: 2/3 (67%)
Deaths: 2/3
GSK3377794+Pembrolizumab
Serious: 2/3 (67%)
Deaths: 0/3

Serious adverse events (6 terms)

ReactionSystemGSK3377794GSK3377794+Pembrolizumab
PancytopeniaBlood and lymphatic system disorders
Atrial flutterCardiac disorders
BronchitisInfections and infestations
PneumoniaInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (77 terms — click to expand)

ReactionSystemGSK3377794GSK3377794+Pembrolizumab
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
White blood cell count decreasedInvestigations
Lymphocyte count decreasedInvestigations
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
Cytokine release syndromeImmune system disorders
HypocalcaemiaMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Atrial fibrillationCardiac disorders
ChillsGeneral disorders
Influenza like illnessGeneral disorders
Mucosal inflammationGeneral disorders
Non-cardiac chest painGeneral disorders
ConstipationGastrointestinal disorders
StomatitisGastrointestinal disorders
Blood lactate dehydrogenase increasedInvestigations
Blood albumin decreasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood calcium increasedInvestigations
Blood phosphorus decreasedInvestigations
Blood potassium decreasedInvestigations
Blood uric acid increasedInvestigations
AmnesiaNervous system disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
HypoaesthesiaNervous system disorders
Immune effector cell-associated neurotoxicity syndromeNervous system disorders
Neuropathy peripheralNervous system disorders

Most-reported serious reactions: Pancytopenia, Atrial flutter, Bronchitis, Pneumonia, Back pain, Tumour pain.

Data from ClinicalTrials.gov NCT03168438 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Lung cancer immunotherapy: progress, pitfalls, and promises.
    Lahiri A, Maji A, Potdar PD, Singh N, et al · · 2023 · cited 737× · PMID 36810079 · DOI 10.1186/s12943-023-01740-y
  2. Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 &lt;sup&gt;c259&lt;/sup&gt;T Cells in Synovial Sarcoma.
    D'Angelo SP, Melchiori L, Merchant MS, Bernstein D, et al · · 2018 · cited 357× · PMID 29891538 · DOI 10.1158/2159-8290.cd-17-1417
  3. NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives.
    Thomas R, Al-Khadairi G, Roelands J, Hendrickx W, et al · · 2018 · cited 298× · PMID 29770138 · DOI 10.3389/fimmu.2018.00947
  4. The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.
    Zhang J, Wang L. · · 2019 · cited 115× · PMID 30798772 · DOI 10.1177/1533033819831068
  5. Unleashing the immune response to NY-ESO-1 cancer testis antigen as a potential target for cancer immunotherapy.
    Raza A, Merhi M, Inchakalody VP, Krishnankutty R, et al · · 2020 · cited 82× · PMID 32220256 · DOI 10.1186/s12967-020-02306-y
  6. Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma.
    Jelinek T, Paiva B, Hajek R. · · 2018 · cited 82× · PMID 30505301 · DOI 10.3389/fimmu.2018.02431
  7. Immune checkpoint inhibitors: breakthroughs in cancer treatment.
    Kong X, Zhang J, Chen S, Wang X, et al · · 2024 · cited 71× · PMID 38801082 · DOI 10.20892/j.issn.2095-3941.2024.0055
  8. Evolution of CD8<sup>+</sup> T Cell Receptor (TCR) Engineered Therapies for the Treatment of Cancer.
    Sun Y, Li F, Sonnemann H, Jackson KR, et al · · 2021 · cited 34× · PMID 34572028 · DOI 10.3390/cells10092379

Verify or expand the search:

Other trials of Letetresgene autoleucel

Trials testing the same drug.

Other recruiting trials for Neoplasms

Currently open trials in the same condition.

Other GlaxoSmithKline trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03168438.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing