scholarly journals Open-Label Pilot Study of Genetically Engineered NY-ESO-1 Specific T Cells (GSK3377794) Alone or in Combination with Pembrolizumab in Relapsed and Refractory Multiple Myeloma

2020 ◽  
Vol 26 (3) ◽  
pp. S269-S270 ◽  
Author(s):  
Taiga Nishihori ◽  
Jonathan L. Kaufman ◽  
James E. Hoffman ◽  
Kristin Blouch ◽  
Sunil Pandit ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Pilot Study ◽  
Genetically Engineered ◽  
Open Label ◽  
Refractory Multiple Myeloma

Open-label pilot study of genetically engineered NY-ESO-1–specific t cells (GSK3377794) alone or in combination with pembrolizumab in relapsed/refractory multiple myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8555-TPS8555
Author(s):  
Aaron Rapoport ◽  
James Edward Hoffman ◽  
Jonathan L. Kaufman ◽  
Kristin Blouch ◽  
Emily Butler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Pilot Study ◽  
Clinical Activity ◽  
Cell Transplant ◽  
Antigenic Peptides ◽  
Single Infusion ◽  
Open Label ◽  
T Cell Therapy ◽  
Refractory Multiple Myeloma

TPS8555 Background: Adoptive cellular therapy may be practice-changing in relapsed/refractory multiple myeloma (MM). NY-ESO-1 TCR T (GSK3377794) are autologous polyclonal T cells transduced by a self-inactivating lentiviral vector to express an affinity-enhanced TCR capable of recognizing NY-ESO-1 or LAGE-1a antigenic peptides in complex with HLA-A*02. GSK3377794 has shown clinical activity in synovial sarcoma, melanoma, myxoid/round cell liposarcoma, and MM after autologous stem cell transplant. NY-ESO-1 and LAGE-1a are cancer/testis antigens frequently overexpressed in MM and linked to poor clinical outcome. PD-1 expression on CD8 T cells, which has been observed in MM patients previously treated with GSK3377794 as well as with CD19 CAR T-cell therapy, can limit adaptive immune response. We hypothesize that GSK3377794 alone, or in combination with the anti-PD-1 inhibitor pembrolizumab, may result in an antitumor effect in MM. Methods: This is an open-label, pilot study (NCT03168438) of GSK3377794 in patients with relapsed/refractory MM positive for HLA-A*02:01, HLA-A*02:05, ± HLA-A*02:06 and NY-ESO-1/LAGE-1a. Patients (n = 20) who have received ≥3 prior therapies containing ≥1 immunomodulatory imide, proteasome inhibitor, alkylator, CD38 monoclonal antibody, or glucocorticoid will be assigned to either single-infusion GSK3377794 (Arm 1, n = 10) or single-infusion GSK3377794 + pembrolizumab 200 mg IV every 3 weeks (Arm 2, n = 10). Arm 1 enrollment will be completed first. In Arm 2, pembrolizumab will begin in Week 3 (Week 6 if precluded by toxicity). Patients in both arms will provide cells via leukapheresis to manufacture autologous NY-ESO-1–specific T cells, undergo lymphodepletion (fludarabine + cyclophosphamide), and then receive GSK3377794 infusion (1−8x109 transduced T cells). Primary and secondary objectives are to assess safety/tolerability and antitumor activity, respectively, of GSK3377794 (± pembrolizumab). Arm 2 enrollment will pause for a 3-week safety review after 3 patients have received a first dose of pembrolizumab. Efficacy, safety, and biomarkers will be assessed every visit. The treatment phase will last 108 weeks, or until disease progression; follow-up will last ≤15 years. As of January 2020, 3 patients have been treated. Funding: GlaxoSmithKline (208470) Clinical trial information: NCT03168438 .

A pilot study of NY-ESO-1c259 T cells in subjects with advanced myxoid/round cell liposarcoma (NCT02992743).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3097-TPS3097 ◽  
Author(s):  
Sandra P. D'Angelo ◽  
Mihaela Druta ◽  
George D. Demetri ◽  
David A. Liebner ◽  
Scott Schuetze ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Pilot Study ◽  
Lentiviral Vector ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Response Duration ◽  
Genetically Engineered ◽  
Round Cell ◽  
Open Label

TPS3097 Background: Myxoid/round cell liposarcomas (MRCLS) account for 6-10% of soft tissue sarcomas. Although a chemosensitive tumor, metastatic MRCLS has a poor prognosis and is inevitably fatal. More effective, durable and less toxic therapies are needed. NY-ESO-1 is a cancer/testis antigen that is expressed in 80-90% of MRCLS tumors. This study will evaluate the safety and efficacy of genetically engineered affinity enhanced autologous NY-ESO-1c259T cells recognizing an NY-ESO-1 derived peptide complexed with HLA-A*02 in MRCLS. Methods: This open label phase I/II non-randomized pilot study will evaluate efficacy (overall response rate by RECIST v1.1, time to response, duration of response, progression free survival, overall survival), safety, and translational research endpoints. Patients must meet these criteria: ≥ 18 yrs old; HLA-A*02:01, *02:05 or *02:06 positive; have advanced (metastatic or inoperable) MRCLS expressing NY-ESO-1 at 2+/3+ intensity in ≥30% of tumor cells by IHC; measurable disease; prior systemic anthracycline therapy; have ECOG status 0 or 1; and adequate organ function. Initially, ten patients are planned to be enrolled, with potential to enroll an additional 5 patients. Patients who do not receive the minimum cell dose or who do not receive the T-cell infusion may be replaced. Following apheresis, the T cells are isolated and expanded with CD3/CD28 beads, transduced with a lentiviral vector containing the NY-ESO-1c259 TCR, and 1– 8 × 109 transduced T-cells are infused intravenously on Day 1 after lymphodepletion with fludarabine 30 mg/m2/day and cyclophosphamide 600 mg/m2/day on days -7 to -5. Response is assessed at 4, 8, 12 and 24 weeks, and then every 3 months until confirmation of progression of disease. On study tumor biopsies and blood samples will be evaluated to compare the pre- and post-T cell infusion immune profile for association with treatment outcome. Clinical trial information: NCT02992743.

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study

2020 ◽  
Vol 21 (2) ◽  
pp. 207-221 ◽  
Author(s):  
Sagar Lonial ◽  
Hans C Lee ◽  
Ashraf Badros ◽  
Suzanne Trudel ◽  
Ajay K Nooka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 2 ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Phase 2 Study ◽  
Open Label Phase

scholarly journals Safety and Efficacy of Anti-Bcma CAR-T Cells for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Literature

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Israr Khan ◽  
Abdul Rafae ◽  
Anum Javaid ◽  
Zahoor Ahmed ◽  
Haifza Abeera Qadeer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cells ◽  
Partial Response ◽  
Residual Disease ◽  
Safety And Efficacy ◽  
Refractory Multiple Myeloma ◽  
Car T Cells ◽  
Car T

Background: Multiple myeloma (MM) is a plasma cell disorder and demonstrates overexpression of B cell maturation antigen (BCMA). Our objective is to evaluate the safety and efficacy of chimeric antigen receptor T cells (CAR-T) against BCMA in patients with relapsed/refractory multiple myeloma (RRMM). Methods: We conducted a systematic literature search using PubMed, Cochrane, Clinicaltrials.gov, and Embase databases. We also searched for data from society meetings. A total of 935 articles were identified, and 610 were screened for relevance. Results: Data from thirty-one original studies with a total of 871 patients (pts) were included based on defined eligibility criteria, see Table 1. Hu et al. reported an overall response rate (ORR) of 100% in 33 pts treated with BCMA CAR-T cells including 21 complete response (CR), 7 very good partial response (VGPR), 4 partial response (PR). Moreover, 32 pts achieved minimal residual disease (MRD) negative status. Chen et al. reported ORR of 88%, 14% CR, 6% VGPR, and 82% MRD negative status with BCMA CAR-T therapy in 17 RRMM pts. In another clinical trial by Han et al. BCMA CAR-T therapy demonstrated an ORR of 100% among 7 evaluable pts with 43% pts having ≥ CR and 14% VGPR. An ORR of 100% with 64% stringent CR (sCR) and 36% VGPR was reported with novel anti-BCMA CART cells (CT103A). Similarly, Li et al. reported ORR of 87.5%, sCR of 50%, VGPR 12.5%, and PR 25% in 16 pts. BCMA targeting agent, JNJ-4528, showed ORR of 91%, including 4sCR, 2CR, 10MRD, and 7VGPR. CAR-T- bb2121 demonstrated ORR of 85%, sCR 36%, CR 9%, VGPR 57%, and MRD negativity of 100% (among 16 responsive pts). GSK2857916, a BCMA targeting CAR-T cells yielded ORR of 60% in both clinical trials. Three studies utilizing bispecific CART cells targeting both BCMA & CD38 (LCARB38M) reported by Zhao et al., Wang et al., and Fan et al. showed ORR of 88%, 88%, & 100% respectively. Topp et al. reported ORR of 31% along with 5 ≥CR and 5 MRD negative status in 42 pts treated with Bi T-cells Engager BiTE® Ab BCMA targeting antigen (AMG420). One clinical trial presented AUTO2 CART cells therapy against BCMA with an ORR of 43%, VGPR of 14%, and PR of 28%. CT053CAR-BCMA showed 14sCR and 5CR with a collective ORR of 87.5% and MRD negative status of 85% in 24 and 20 evaluable pts, respectively. Likewise, Mikkilineni et al. reported an ORR of 83%, sCR of 16.7%, and VGPR & PR of 25% and 41% in 12 pts treated with FHVH-BCMA T cells. Similar results are also reported in other clinical trials of BCMA targeting CART therapy (Table 1). The most common adverse effects exhibited were grade 1-3 hematologic (cytopenia) and cytokine release syndrome (CRS) (mostly reversible with tocilizumab). Conclusion: Initial data from ongoing clinical trials using BCMA targeting CAR-T therapy have yielded promising results both in terms of improved outcome and tolerable toxicity profiles. Although two phase 3 trails are ongoing, additional data is warranted to further ensure the safety and efficacy of anti-BCMA CAR-T cells therapy in pts with RRMM for future use. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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