Last updated: 11/10/2021 12:10:07
Letetresgene autoleucel Engineered T cells alone and in combination with pembrolizumab in NY-ESO-1 Positive Multiple Myeloma
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
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
Trial 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Up to 108 weeks
Number of participants with treatment limiting toxicities-GSK3377794+pembrolizumab arm only
Timeframe: Up to 3 weeks
Number of participants with worst-case chemistry results by any grade increase post-Baseline relative to Baseline
Timeframe: Up to 108 weeks
Number of participants with worst-case hematology results by any grade increase post-Baseline relative to Baseline
Timeframe: Up to 108 weeks
Number of participants with worst-case results for coagulation parameters relative to normal range post-Baseline relative to Baseline
Timeframe: Up to 108 weeks
Number of participants with worst-case post Baseline abnormal electrocardiogram (ECG) findings
Timeframe: Up to 108 weeks
Secondary outcomes:
Overall response rate
Timeframe: Up to 108 weeks
Time to response
Timeframe: Up to 108 weeks
Duration of response
Timeframe: Up to 108 weeks
Progression-free survival
Timeframe: Up to 108 weeks
Maximum persistence (Cmax) of GSK3377794
Timeframe: Up to 108 weeks
Time to maximum persistence
Timeframe: Up to 108 weeks
Area under the plasma concentration-time curve from zero to Day 28 (AUC[0-28])
Timeframe: Up to Day 28
Interventions:
Enrollment:
6
Primary completion date:
2020-13-07
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms
Product
GSK3371846, GSK3377794, cyclophosphamide, fludarabine
Collaborators
Merck Sharp and Dohme Corp.
Study date(s)
August 2017 to November 2020
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21201
Status
Study Complete
Location
GSK Investigational Site
Duarte, California, United States, 91010
Status
Study Complete
Location
GSK Investigational Site
Tampa, Florida, United States, 33612-9497
Status
Study Complete
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30322
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2020-13-07
Actual study completion date
2020-05-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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