RN1701 Injection in the Treatment of Relapsed/Refractory B-Cell Lymphomas

An Exploratory Clinical Study of the Safety and Efficacy of RN1701 Injection in the Treatment of Relapsed/Refractory B-Cell Lymphomas

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed/Refractory B-cell Lymphoma
• Intervention / Treatment: Biological: RN1701 injection

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wenyu Shi; Phone Number: 13515203737; Email: shiwenyu@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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.
5. At least one measurable lesion per Lugano criteria: nodal lesion longest diameter >1.5 cm, extranodal lesion >1.0 cm.

6. Prior treatment response must meet one of the following:

   • Large B-cell lymphoma, grade 3B follicular lymphoma, transformed indolent lymphoma: i. Primary refractory and ineligible/unable to receive autologous CAR-T: best response PD after ≥2 cycles of first-line therapy, or SD after ≥4 cycles.

   ii. Relapse ≤12 months after achieving CR with first-line chemo-immunotherapy. iii. Relapse/progression ≤12 months after autologous HSCT. iv. Refractory to, relapsed after, or progressed on ≥2 prior lines (including autologous CAR-T): best response PD or SD after ≥2 cycles of the most recent regimen.

   v. Transformed indolent lymphoma: prior chemotherapy for iNHL and ≥1 systemic regimen after transformation, fulfilling the above refractory/relapse criteria.

   • Grade 1, 2, or 3A follicular lymphoma: i. Primary refractory and ineligible/unable to receive autologous CAR-T: best response PD after ≥2 cycles of first-line therapy.

   ii. Refractory to, relapsed after, or progressed on ≥2 prior lines (including autologous CAR-T): best response PD or SD after ≥2 cycles of the most recent regimen.

   • Mantle-cell lymphoma: i. Primary refractory and ineligible/unable to receive autologous CAR-T: best response PD after ≥2 cycles of first-line therapy, or SD after ≥4 cycles.

   ii. Refractory to, relapsed after, or progressed on ≥2 prior lines (including autologous CAR-T): best response PD or SD after ≥2 cycles of the most recent regimen.

7. Estimated life expectancy ≥3 months.

8. Screening laboratory values (may be repeated once):

   • Hemoglobin ≥8.0 g/dL (no transfusion within 7 days).
   • Platelets ≥50×10⁹/L (no transfusion within 7 days).
   • ANC ≥1.0×10⁹/L (growth-factor support allowed if none within 7 days of test).
   • AST/ALT ≤3×ULN (≤5×ULN if liver involvement).
   • Serum creatinine ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault).
   • Total bilirubin ≤2×ULN (≤3×ULN if liver involvement); except congenital bilirubin disorders (e.g., Gilbert's syndrome: direct bilirubin ≤1.5×ULN).
   • INR, PT, APTT <1.5×ULN.
9. Toxicities from prior anti-cancer therapy (except alopecia, nausea, and the above lab values) must have stabilized at baseline or resolved to ≤Grade 1.
10. WOCBP must have a negative high-sensitivity serum β-hCG pregnancy test at screening and again before the first dose of cyclophosphamide/fludarabine.
11. Subjects of reproductive potential must use effective contraception for ≥12 months after completing study therapy.

Exclusion Criteria:

• Subjects with any of the following conditions are ineligible for this trial:

  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.
  5. Prior allogeneic haematopoietic stem-cell transplantation.
  6. Positive donor-specific antibody (DSA).

  7. At least one of the following high-risk features:

     • Sum of the product of perpendicular diameters (SPD) of all measurable lesions ≥100 cm²;
     • Bulky disease: single mass ≥7.5 cm; mediastinal mass with maximum diameter >1/3 of thoracic diameter;
     • Obstructive/compressive emergency (e.g., bowel obstruction, vascular compression) requiring urgent intervention at screening.
  8. Active CNS involvement (symptomatic or positive CSF/imaging); subjects with prior CNS disease now in remission (asymptomatic with negative CSF and imaging) are eligible.
  9. Significant bleeding diathesis: gastrointestinal bleeding, haemorrhagic cystitis, coagulopathy, hypersplenism (splenomegaly on exam/US, cytopenias, hyperplastic marrow) or ongoing anticoagulation.
  10. Chronic concomitant systemic corticosteroids or other immunosuppressants, except: topical, ocular, intra-articular, nasal or inhaled corticosteroids; short-course steroids for prophylaxis (e.g., contrast allergy).

  11. Severe underlying medical conditions:

      • Active serious viral, bacterial or uncontrolled systemic fungal infection;
      • Active systemic autoimmune disease requiring therapy.

  12. Significant cardiac disease:

      • NYHA class III or IV congestive heart failure;
      • Myocardial infarction or CABG within 6 months before enrolment;
      • Clinically relevant ventricular arrhythmia or unexplained syncope not vasovagal or dehydration-related;
      • Severe non-ischaemic cardiomyopathy;
      • Left ventricular ejection fraction (LVEF) <45% by echo or MUGA within 4 weeks before lymphodepletion.
  13. Resting oxygen saturation <92%.
  14. Clinically relevant prior or current CNS disorder: epilepsy, seizure-like episodes, paralysis, aphasia, stroke, severe head trauma, dementia, Parkinson's disease, cerebellar disorder, organic brain syndrome or major psychiatric illness.
  15. Live-attenuated vaccine within 4 weeks before screening.
  16. Major surgery within 2 weeks before screening or planned within 2 weeks after study treatment (local anaesthesia allowed).
  17. Positive screen for HBsAg, HBeAg, HBV DNA, HCV antibody, HCV RNA, or HIV antibody.
  18. Life-threatening allergy, hypersensitivity or intolerance to study-drug excipients including, but not limited to, DMSO.
  19. Lactating women.
  20. Any condition that, in the investigator's opinion, renders the subject unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relapsed/refractory B-cell lymphoma; Relapsed/refractory B-cell lymphoma patients to be treated with a single dose of RN1701 cells	Biological: RN1701 injection; RN1701 injection is a bispecific CD19/CD20-targeted allogeneic CAR-T. A single infusion of CAR-T cells will be administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity and adverse event grading after RN1701 treatment	all toxicities and AEs will be assessed according to the National Cancer Institute CTCAE v5.0	up to 12 months after infusion
CRS grading after RN1701 treatment	CRS will be graded using the Lee DW et al. CRS grading scale. Grade 1: Fever, mild symptoms, manageable with supportive care Grade 2: Moderate symptoms (eg, hypotension, hypoxia), requires intervention (eg, intravenous fluids, antipyretics) Grade 3: Severe symptoms (eg, multiorgan involvement), requires corticosteroids and tocilizumab Grade 4: Life-threatening, requires intensive care unit (ICU) care and urgent interventions	up to 12 months after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR =CR + PR) of patients receive RN1701 treatment	according to the Lugano criteria and CSCO guidelines	1，3，6，and 12months after infusion
Disease control rate (DCR=CR +PR +SD) of patients receive RN1701 treatment	according to the Lugano criteria and CSCO guidelines	1, 3, 6 and 12 months after infusion
Assessment includes contrast enhanced CT of head/neck, chest, abdomen,and pelvis, plus whole-body PET-CT	Tumor measurements and evaluations must be performed with the same technique used at baseline	1，3，6，and 12 months after infusion
CAR copies of CAR-T in blood after RN1701 treatment	CAR copies in copies/ug genome DNA	Days 0, 1, 3, 5, 7, 9,11, 14, 21, 28 and month 2, 3, 6, 9, 12 after infusion
Cell count of CAR-T in blood after RN1701 treatment	Cell count of CAR-T in cells/ul	Days 0, 1, 3, 5, 7, 9,11, 14, 21, 28 and month 2, 3, 6, 9, 12 after infusion

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Nantong University

Study record dates

Study Major Dates

• Study Start (Estimated): March 23, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): May 30, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 28, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell
• Other Study ID Numbers: 2026-K054-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No