This single-arm, open-label pilot study will assess the safety and efficacy of RN1701, a bispecific CD19/CD20-targeted allogeneic CAR-T-cell product, in patients with relapsed or refractory B-cell lymphoma. Up to 19 participants will be enrolled in a conventional 3 + 3 dose-escalation scheme. The primary objective of the study is to evaluate the safety and feasibility of RN1701 for the treatment of relapsed/refractory B-cell lymphoma. The secondary objective is to evaluate the efficacy of RN1701 for the treatment of relapsed/refractory B-cell lymphoma. The exploratory objective is to evaluate the expansion, persistence, and ability of RN1701 to deplete CD19- and/or CD20-positive cells in patients with relapsed/refractory B-cell lymphoma.
1. Voluntary participation; full understanding of the study and provision of written informed consent obtained before any study-related procedure not part of standard care; willingness to comply with follow-up.
2. Age 18-75 years; either sex.
3. ECOG performance status 0-1.
4. Histologically confirmed large B-cell lymphoma, follicular lymphoma, mantle-cell lymphoma, or indolent lymphoma transformed to DLBCL; CD19 and/or CD20 positive.
1. Any malignancy other than B-cell non-Hodgkin lymphoma ever diagnosed or treated, except: • Malignancy that received curative therapy and has shown no evidence of active disease for ≥2 years before enrolment; or • Adequately treated non-melanoma skin cancer with no current evidence of disease.
2. Prior anti-cancer therapy within the stated windows (before lymphodepletion): • CNS prophylaxis (e.g., intrathecal methotrexate and/or cytarabine) within 7 days; • Cytotoxic chemotherapy or radiotherapy within 14 days; • Small-molecule targeted or epigenetic therapy within 14 days or 5 half-lives, whichever is longer; • Monoclonal antibody, bispecific antibody, or antibody-drug conjugate within 21 days or 5 half-lives, whichever is shorter; • Investigational drug or invasive investigational device within 28 days (if the therapy is also investigational, the 28-day wash-out applies); • Autologous haematopoietic stem-cell transplant or CD19-directed autologous CAR-T therapy within 100 days.
3. Any autologous cellular or gene therapy other than CD19-directed autologous CAR-T.
4. Any allogeneic cellular (including CAR-T) or gene therapy.