a clinical study of onct-808 in subjects with relapsed or refractory b-cell malignancies

Conditions: Relapsed/Refractory Aggressive B-Cell Malignancies

Summary: this is a phase 1/2 study to investigate the safety and efficacy of the car-t therapy, onct-808, in patients with relapsed/refractory (r/r) aggressive b cell malignancies.

study onct-808-101 is a phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of onct-808 in subjects with aggressive b cell lymphoma (bcl), including large b-cell lymphoma (lbcl) and mantle cell lymphoma (mcl). the study will be separated into two distinct phases designated as phase 1 and phase 2. after the safety and tolerability of onct-808 have been assessed to select the recommended phase 2 dose (rp2d) in phase 1, phase 2 will commence to further validate the dose and evaluate the safety and efficacy of onct-808. in phase 2, subjects with lbcl or mcl will be enrolled into 2 separate dose expansion cohorts.

Eligibility criteria:
key inclusion criteria: * over 18 years old * histologically confirmed aggressive b-cell nhl, including: * mcl, with diagnosis confirmed by cyclin d1 overexpression or evidence of t (11;14) translocation * lbcl, including: * dlbcl nos * primary mediastinal lbcl * high-grade bcl * dlbcl arising from follicular lymphoma * follicular lymphoma grade 3b * richter's syndrome * availability of archival tissue for immunohistology, or willing to undergo baseline biopsy if not available * r/r with no available therapy. subject must have: * received prior systemic therapy that has included an alkylating agent, anthracycline, and an anti-cd20 mab * received and progressed after autologous hematopoietic stem cell transplant (hsct) or is ineligible for or has refused to receive hsct * received prior approved cd19 car t-cell therapy or is ineligible for or has refused cd19 car-t * minimum washout period between previous systemic therapy and leukapheresis includes: * chemotherapy: at least 14 days or 5 half-lives, whichever is shorter * autologous hsct: at least 3 months * cd19 car t-cell therapy: at least 6 months * ≥1 measurable lesion per lugano criteria (cheson, 2014) * subject has fluorodeoxyglucose (fdg)-avid disease. * subject has an ecog performance status of 0 or 1. * subject has adequate organ function: * alc ≥100/ul * anc ≥1000/ul (≥500/ul if due to lymphoma; growth factors allowed) * hgb ≥8 g/dl (transfusion allowed) * platelets ≥75,000/ul (≥50,000/ul if due to lymphoma; transfusion allowed) * crcl ≥50 ml/min; ast/alt ≤2.5x uln, t. bili ≤1.5 mg/dl (except gilbert's) * ef ≥50% by echo/muga; ncs ecg, ncs pleural effusion; o2 sat \>92% * subject has an estimated life expectancy of \>12 weeks key exclusion criteria: * prior ror1-targeted therapy * current or anticipated systemic immunosuppressive therapy (e.g., prednisone \>5 mg) from ld chemo until day 28 post onct-808 dosing * if receiving anticoagulation therapy, subject is unable to hold therapy for 3 days prior and 28 days following onct-808 administration * known cns involvement by malignancy within 6 months * h/o or current cns disorder (e.g., seizure, cva, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome or any autoimmune disease with cns involvement) within 6 months of study entry * clinically significant cardiovascular disease (e.g., mi, ua, cabg, or chf grade ≥2 nyha within 12 months of planned onct-808 dosing) or serious arrhythmia requiring medication * evidence of hiv infection or active hbv, hcv * systemic fungal infection requiring medication in the last 12 months * h/o covid-19 infection with residual lung infiltrate/fibrosis * h/o other malignancy except non-melanoma skin cancer or carcinoma in situ not in remission for ≥2 years * h/o autoimmune disease resulting in end organ injury or require systemic immunosuppression within last 2 years * h/o allogeneic hsct or organ transplant

Keywords: lymphoma lymphoma, b-cell lymphoma, large b-cell, diffuse lymphoma, mantle cell lymphoproliferative disorders lymphatic diseases immunoproliferative disorders immune system diseases lymphoma, non-hodgkin ror1 car-t cell therapy autologous car-t cell therapy adoptive cellular therapy cellular immunotherapy