Clinical trial NCT03168438: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Relapsed and Refractory Multiple Myeloma
T Cell Receptor
Immuno-oncology
NY-ESO-1
Leukapheresis
Adoptive TCR T-cell therapy
Letetresgene autoleucel
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-05-30
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 108 weeks
measure: Number of Participants With Treatment Limiting Toxicities-GSK3377794+Pembrolizumab Arm Only
timeFrame: Up to 3 weeks
measure: Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to 108 weeks
measure: Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to 108 weeks
measure: Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline
timeFrame: Up to 108 weeks
measure: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to 108 weeks
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Up to 108 weeks
measure: Time to Response
timeFrame: Up to 108 weeks
measure: Duration of Response
timeFrame: Up to 108 weeks
measure: Progression-free Survival
timeFrame: Up to 108 weeks
measure: Maximum Persistence (Cmax) of GSK3377794
timeFrame: Up to 108 weeks
measure: Time to Maximum Persistence
timeFrame: Up to 108 weeks
measure: Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC[0-28])
timeFrame: Up to Day 28
Other outcomes:
Locations:
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: