A Phase 1 / 2 Study to Evaluate the Safety and Tolerability of Adoptively Transferred Autologous T Cells in Patients With Relapsed Refractory Multiple Myeloma
This Research study is being done to characterize the safety, tolerability, and preliminary antitumor activity of the NEXI-002 T cell product (a new experimental therapy), which contains populations of CD8+ T cells targeting multiple Myeloma associated antigen peptides in patients with relapsed refractory multiple myeloma (MM). The study will enroll patients with MM who have relapsed or are refractory to standard lines of treatment. The enrolled patients will undergo bridging therapy for the purposes of disease control while the NEXI-002 T cell product is being manufactured. Choice of bridging therapy administered will be per the Investigator's discretion, but is limited to acceptable agents as specified in the protocol. Bridging therapy will be administered prior to lymphodepleting (LD) therapy, with the last dose of the bridging therapy administered ≥ 14 days prior to initiation of LD therapy. Within 72 hours after completing LD therapy, patients will receive a single IV infusion of the NEXI-002 T cell product.
• Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the patient's disease. Patients must also be willing and able to comply with study procedures, including the acquisition of specified research specimens
• Age ≥ 18 years old \& life expectancy \> 3 months
• Expression of HLA-A\*0201 as determined by high resolution sequence-based typing method
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with exception of ECOG \> 1 if related to recent bone fracture
• Patients must have confirmed diagnosis of MM
• Have identified relapsed/refractory disease which includes:
∙ Previous therapy consisting of at least three (3) standard regimens, including a proteasome inhibitor, IMiD, or anti-CD38 targeting therapy.
∙ Note: Induction therapy, autologous stem cell transplantation (ASCT) \& maintenance therapy if given sequentially without intervening progressive disease (PD) are considered one 'regimen'
‣ Refractory MM may be defined as disease that is refractory to treatment while on therapy or that shows progression within 60 days of the last therapy.
• Have measurable disease as defined by:
∙ Serum M protein ≥ 0.5 g/dL
‣ Urine M protein ≥ 200 mg/24hr
‣ Serum free light chains (FLC) ≥ 10 mg/dL with abnormal FLC ratio Note: Patients with IgA MM in whom serum protein electrophoresis (sPEP) is deemed unreliable, due to co-migration of normal serum proteins with the paraprotein in the β region, may be considered eligible as long as total serum IgA level is \> normal range.
• Acceptable laboratory parameters as follows:
∙ AST/ALT ≤ 2.5 × ULN
‣ Total bilirubin ≤ 1.5 × ULN, except patients with Gilbert's syndrome, who may enroll if the conjugated bilirubin is within normal limits
‣ Serum creatinine ≤ 2.5 mg/dL or estimated creatinine clearance (CL) ≥ 30 mL/min \& not dialysis-dependent
‣ ALC \> 1000 cells/µL
• Recovery to Grade 1 or baseline of non-hematologic toxicities from prior treatments, excluding alopecia \& Grade 2 peripheral neuropathy
⁃ Female patients of childbearing potential must test negative for pregnancy at enrollment and during the study. Sexually active women of child-bearing potential, unless surgically sterile, must be willing to use a highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs) or vasectomized partner
⁃ Male patients with partners of childbearing potential must be either vasectomized or agree to use a condom in addition to having their partners use another method of contraception resulting in a highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, or IUDs. Patients should not have sexual intercourse with females who are either pregnant or lactating without double-barrier contraception • Is not pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through one year from administration of NEXI-002 T cells