A Phase 1b Study Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of NT-I7 (Efineptakin Alfa), a Long-acting Human IL-7, Post-Axicabtagene Ciloleucel or Post-Lisocabtagene Maraleucel in Subjects With Relapsed/Refractory Large B-cell Lymphoma
Diffuse large B-cell lymphoma is the most commonly occurring subtype of non-Hodgkin lymphoma, but treatment is often not curative, with as many as 50% of patients with adverse risk factors developing relapsed/refractory disease. CAR T-cell therapy has revolutionized modern cancer therapy, with axicabtagene ciloleucel and lisocabtagene maraleucel (anti-CD19 CAR T-cell therapies) FDA approved for second- or later-line treatment of relapsed/refractory large B-cell lymphoma. IL-7 plays a crucial role in T-cell homeostasis by inducing thymic differentiation, peripheral expansion, and extrathymic differentiation. It is the main regulator of T-cell hemostasis, inducing T-cell growth and proliferation in lymphopenic patients. There is data that suggests that exposure of T-cells to IL-7 may expand T-cells, prevent T-cell exhaustion, and improve effector functions. NT-I7 is a long-acting human IL-7 cytokine which has been shown in nonclinical studies to increase peripheral T-cells, antitumor efficacy, and tumor infiltrating lymphocytes, either as a monotherapy or in combination with chemo/radiotherapy and/or immune checkpoint inhibitors and CAR T therapy. This study is testing the hypothesis that the administration of NT-I7 following standard of care (SOC) approved CD19 CAR T-cell therapies for subjects with relapsed/refractory large B-cell lymphoma (LBCL) will be safe and tolerable and may increase the expansion and persistence of CAR T-cells in vivo, which may result in increased tumor response rate and improved clinical outcomes.
• Histologically confirmed relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high grade B-cell lymphoma, DLBCL arising from an indolent lymphoma, grade 3B follicular lymphoma and primary mediastinal large B-cell lymphoma.
• Measurable disease by IWG response criteria for lymphoma.
‣ Baseline FDG-PET/CT scan must show FDG-avid lesions compatible with CT-defined anatomical tumor sites.
⁃ A previously irradiated lesion can be considered a target lesion if it is well defined, measurable, and has clearly progressed following radiation.
⁃ FDG-PET/CT scans done as SOC up to 60 days pre-lymphodepletion therapy will be allowed. NOTE: After eligibility is confirmed, restaging FDG-PET/CT scans will not be used to change eligibility.
• Eligible for treatment with an FDA-approved SOC CD19 CAR T-cell therapy respective to the current FDA-approved CAR T-cell label for axi-cel(Yescarta®) or liso-cel (Breyanzi®).
• If the patient has previously received an autologous stem cell transplant, s/he must be at least 3 months post-transplant.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate bone marrow and organ function at the start of lymphodepleting chemotherapy as pre-conditioning for SOC CD19 CAR T-cell infusion as defined below:
‣ Absolute neutrophil count ≥ 1.0 K/cumm
⁃ Platelets ≥ 50 K/cumm
⁃ Hemoglobin ≥ 8.0 g/dL
⁃ Total bilirubin ≤ 1.5 x IULN or direct bilirubin ≤ IULN for patients with total bilirubin levels \> 1.5 x IULN (except for patients with Gilbert's syndrome, who must have a baseline total bilirubin ≤ 3.0 mg/dL)
⁃ AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (except for patients with documented liver involvement or bone metastases, who must have an AST and/or ALT ≤ 5.0 x IULN)
⁃ Alkaline phosphatase ≤ 2.5 x IULN (except for patients with liver metastasis, who must have an alkaline phosphatase ≤ 5.0 x IULN)
⁃ Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
⁃ INR and aPTT ≤ 1.5 x IULN unless the patient is receiving anticoagulant therapy and the PT or aPTT is within the therapeutic range for the anticoagulant. Patients who are on anticoagulation should be able to hold the anticoagulant for 4-5 half-lives of the anticoagulant prior to IM NT-I7 injection to reduce risk of hematoma.
• ECG demonstrating Fridericia's corrected QT interval (QTcF) \< 500 ms; patients with QTcF ≥ 500 ms will require clearance by a cardiologist.
• The effects of NT-I7 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days after the last NT-I7 injection. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.