Clinical Trials /

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

NCT03168438

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 208470
  • SECONDARY ID: ADP-0011-008
  • SECONDARY ID: KEYNOTE-487
  • NCT ID: NCT03168438

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
Letetresgene autoleucelArm 1: Letetresgene autoleucel (GSK3377794)
Letetresgene autoleucel with pembrolizumabArm 2: Letetresgene autoleucel (GSK3377794) with pembrolizumab
FludarabineArm 1: Letetresgene autoleucel (GSK3377794)
CyclophosphamideArm 1: Letetresgene autoleucel (GSK3377794)
PembrolizumabArm 2: Letetresgene autoleucel (GSK3377794) with pembrolizumab

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Letetresgene autoleucel (GSK3377794)ExperimentalEligible 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.
  • Letetresgene autoleucel
  • Fludarabine
  • Cyclophosphamide
Arm 2: Letetresgene autoleucel (GSK3377794) with pembrolizumabExperimentalEligible 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 with pembrolizumab
  • Fludarabine
  • Cyclophosphamide
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Age >=18 years of age or older on the date of signing informed consent.

          -  Histologically confirmed diagnosis of secretory multiple myeloma with myeloma markers
             at levels defined in the protocol.

          -  Documented diagnosis of relapsed and refractory multiple myeloma (RRMM) (at least 3
             prior regimens and responsive to at least 1, and refractory to most recent prior
             therapies, which must have included one or more than one drug from each of the
             following drug classes: an immunomodulatory imide drug (IMiD), proteasome inhibitor,
             alkylator (unless the participant is ineligible or contraindicated to receive an
             alkylator), CD 38 monoclonal antibody, and glucocorticoid as separate lines or a
             combined line of therapy.- Left ventricular ejection fraction (LVEF) >= 50%. Lower
             LVEF (>= 40%) permissible if formal cardiologic evaluation reveals no evidence for
             clinically significant functional impairment.

          -  Meets protocol criteria for patients who have previously received checkpoint
             inhibitors or other immuno-oncology agents.

          -  ECOG Performance Status 0 or 1.

          -  Participant is HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 positive as determined by
             a designated central laboratory.

          -  Participant has confirmed sufficient expression of NY-ESO-1 and/or LAGE-1a as
             determined by a designated central laboratory.

          -  In the Investigator's opinion, the participant is fit for cell collection.

          -  Participant has adequate organ function and cell counts as described in the protocol.

          -  Participants previously treated with BCMA therapy (BCMA chimeric antigen receptor
             (CAR)-T, antibody-drug conjugate (ADC), or other type of BCMA-targeted therapy) must
             have progressed from this therapy prior to attending the Baseline visit prior to
             beginning lymphodepletion.

          -  Contraception use by male and female participant meets protocol requirements.

        Exclusion Criteria:

          -  Has only plasmacytomas, plasma cell leukemia, monoclonal gammopathy of undetermined
             significance (MGUS), smoldering multiple myeloma (SMM), non-secretory myeloma or
             primarily amyloidosis.

          -  Previously received anti- programmed death (PD)-1, anti-PD-ligand (L)1, or anti-PD-L2
             inhibitor.

          -  Previously participated in Merck pivotal trial NCT02576977: Study of Pomalidomide and
             Low Dose Dexamethasone With or Without Pembrolizumab in Refractory or RRMM.

          -  Had a prior allogeneic stem cell transplant.

          -  Has ongoing toxicity from previous anticancer therapy.

          -  Had a major surgery within 4 weeks prior to enrollment.

          -  Has history of allergic reactions to fludarabine, cyclophosphamide or agents similar
             to fludarabine, cyclophosphamide or other agents used in the study.

          -  Known history of myelodysplasia.

          -  Current active liver or biliary disease.

          -  Known history of chronic active hepatitis or liver cirrhosis.

          -  Participant has an active viral infection.

          -  History of severe immune disease, including non-infectious pneumonitis, requiring
             steroids or other immunosuppressive treatments.

          -  Active immune-mediated diseases.

          -  Prior or active demyelinating disease.

          -  Evidence or history of significant cardiac disease.

          -  Evidence or history of other significant, hepatic, renal, ophthalmologic, psychiatric,
             or gastrointestinal disease.

          -  Participants with concomitant second malignancies (except adequately treated
             non-melanomatous skin cancers, carcinoma in situ of the breast, treated superficial
             bladder cancer or prostate cancer, or in situ cervical cancers ) not in complete
             remission.

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
             Participants with previously treated brain metastases may be eligible.

          -  Active bacterial or systemic viral or fungal infections.

          -  Pregnant or breastfeeding.

          -  Cannot meet washout periods for prior radiotherapy, chemotherapy or other
             protocol-specified therapies.

          -  More than 2 years have passed since the participant's last leukapheresis collection.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events (AEs)and serious adverse events (SAEs)
Time Frame:Up to 108 weeks
Safety Issue:
Description:AEs and SAEs will be collected

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 108 weeks
Safety Issue:
Description:Overall Response Rate is defined as the proportion of participants with a confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR) using IMWG uniform response criteria for MM
Measure:Time to Response (TTR)
Time Frame:Up to 108 weeks
Safety Issue:
Description:Time to response is defined as the time from date of T-cell infusion to initial date of response of the participant who achieved confirmed sCR, CR, VGPR or PR
Measure:Duration of Response (DOR) for all participants who achieve at least PR
Time Frame:Up to 108 weeks
Safety Issue:
Description:Duration of response is defined as the time from the initial date of response of the participants who achieved confirmed sCR, CR, VGPR or PR to the date of progressive disease or death
Measure:Progression-free survival (PFS)
Time Frame:Up to 108 weeks
Safety Issue:
Description:Progression free survival is defined as the time from the date of T cell infusion until first documented sign of disease progression or death due to any cause.
Measure:Maximum persistence (Cmax)
Time Frame:Up to 108 weeks
Safety Issue:
Description:Serial blood samples will be collected at specific timepoints for evaluation of Cmax.
Measure:Time to Cmax (Tmax)
Time Frame:Up to 108 weeks
Safety Issue:
Description:Serial blood samples will be collected at specific timepoints for evaluation of Tmax.
Measure:Area under the time curve from zero to time t (AUC 0-t)
Time Frame:Up to 108 weeks
Safety Issue:
Description:Serial blood samples will be collected at specific timepoints for evaluation of AUC (0 to t).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Relapsed and Refractory Multiple Myeloma
  • T Cell Receptor
  • Immuno-oncology
  • NY-ESO-1
  • Leukapheresis
  • Adoptive TCR T-cell therapy
  • Letetresgene autoleucel

Last Updated

February 25, 2021