In‑body CAR‑T generation with PIC1 injection for relapsed or refractory B‑cell non‑Hodgkin lymphoma.

Clinical Study of PIC1 Injection for the Treatment of Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

This will try a single intravenous PIC1 injection to create CAR‑T cells inside the body for adults with relapsed or refractory B‑cell non‑Hodgkin lymphoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: CAR-T, Chimeric Antigen Receptor, chemotherapy, Radiation
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07456371 on ClinicalTrials.gov

What this trial studies

This open‑label, single‑arm phase 1 study gives an intravenous PIC1 injection designed to generate CAR‑T cells in vivo for adults with relapsed or refractory B‑cell non‑Hodgkin lymphoma. Participants are hospitalized after infusion for close monitoring of safety and early responses. The study follows patients for up to two years to track disease control and long‑term safety. Key outcomes include safety signals, anti‑tumor activity, and durability of response.

Who should consider this trial

Good fit: Adults aged 18 to 75 with histologically or cytologically confirmed relapsed or refractory B‑cell non‑Hodgkin lymphoma (including DLBCL, HGBL, primary mediastinal large B‑cell lymphoma, T‑cell/histiocyte‑rich large B‑cell lymphoma, and transformed DLBCL) are the intended participants.

Not a fit: Patients outside the 18–75 age range, with non‑B‑cell lymphomas, or with medical conditions that prevent safe hospitalization or IV cellular therapies are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could allow CAR‑T cells to be made inside the patient, offering a faster, simpler alternative to current manufactured CAR‑T therapies and potentially expanding access.

How similar studies have performed: In‑body CAR‑T generation is a relatively novel approach with limited clinical data so far and most supporting evidence comes from early‑stage or preclinical work.

Eligibility criteria

Inclusion Criteria:

* The patient (or their legally authorized representative) has voluntarily agreed to participate in this clinical trial and has signed the Informed Consent Form (ICF), indicating full understanding of the study's objectives and procedures.
* Aged 18 to 75 years, regardless of gender.
* Histologically or cytologically confirmed B-cell Non-Hodgkin Lymphoma (NHL) according to the WHO 2017 classification, including the following subtypes:

  1. Diffuse Large B-Cell Lymphoma (DLBCL): Including DLBCL, not otherwise specified (DLBCL, NOS); DLBCL associated with chronic inflammation; Primary Cutaneous DLBCL, leg type; and EBV-positive DLBCL, NOS.
  2. High-Grade B-Cell Lymphoma (HGBL): Including HGBL, NOS; and HGBL with MYC and BCL2 and/or BCL6 rearrangements.
  3. Primary Mediastinal Large B-Cell Lymphoma.
  4. T-cell/Histiocyte-rich Large B-Cell Lymphoma.
  5. Transformed DLBCL: DLBCL transformed from prior lymphomas (e.g., Follicular Lymphoma, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Marginal Zone Lymphoma).
  6. Follicular Lymphoma Grade 3b (FL3b).
  7. Mantle Cell Lymphoma.
* Patients must have received adequate prior therapy including an anti-CD20 monoclonal antibody and an anthracycline, unless contraindicated or intolerant (i.e., CD20-negative status, intolerance to anti-CD20 mAb, or contraindication to anthracyclines). Patients must meet the definition of Relapsed or Refractory (R/R) disease:

  1. Relapsed: Disease progression or recurrence after achieving a Complete Response (CR) to standard therapy.
  2. Refractory: Best response of Stable Disease (SD) after at least 4 cycles of first-line therapy or at least 2 cycles of last-line therapy (≥2nd line), with SD duration ≤6 months after the last dose; or best response of Progressive Disease (PD) to the last treatment.
  3. No response, disease progression, or relapse after Autologous Stem Cell Transplantation (ASCT).
  4. Patients with transformed lymphoma who received chemotherapy prior to transformation and subsequently failed to achieve response, progressed, or relapsed after salvage therapy post-transformation.
* CD19 positivity confirmed by immunohistochemistry (IHC) or flow cytometry.
* ECOG performance status of 0 or 1.
* Estimated life expectancy of ≥12 weeks.
* At least one measurable lesion per the 2014 Lugano Criteria:

  1. For nodal lesions: Longest diameter \>1.5 cm.
  2. For extranodal lesions: Longest diameter \>1.0 cm.
* Adequate major organ function defined as:

  1. Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥40% by echocardiogram.
  2. Renal function: Serum creatinine ≤2.0 × ULN or Creatinine Clearance ≥50 mL/min (calculated by Cockcroft-Gault formula).
  3. Hepatic enzymes: ALT and AST ≤3.0 × ULN (or ≤5.0 × ULN for subjects with hepatic involvement).
  4. Bilirubin: Total bilirubin ≤2.0 × ULN (or ≤3.0 × ULN for subjects with Gilbert's syndrome).
  5. Oxygenation: Oxygen saturation (SpO2) ≥ 92% while breathing room air.
  6. Hematology: Neutrophil Count ≥ 1.0 × 10\^9/L; Platelet count ≥ 75 × 10\^9/L; Hemoglobin ≥ 80 g/L. (For subjects with bone marrow involvement: Neutrophil ≥ 0.5 × 10\^9/L and Platelet count ≥ 50 × 10\^9/L.)
* Women of childbearing potential must have a negative pregnancy test. All subjects must agree to use a highly effective method of contraception from the time of signing the ICF until 1 year after the infusion of the investigational product.

Exclusion Criteria:

* Received prior Chimeric Antigen Receptor T-cell (CAR-T) therapy or any other gene-modified cell therapy before screening.
* Received any of the following anti-tumor therapies prior to PIC1 infusion:

  1. medications (e.g., chemotherapy, targeted therapy) within 14 days or 5 half-lives (whichever is longer) before infusion. (excluding lymphodepleting chemotherapy and intrathecal chemotherapy for CNS lymphoma. And intrathecal chemotherapy must be discontinued at least 1 week prior to PIC1 infusion.)
  2. Radiation therapy within 14 days before infusion.
* Has any of the following cardiac conditions:

  1. New York Heart Association (NYHA) Class III or IV congestive heart failure.
  2. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to enrollment.
  3. Clinically significant ventricular arrhythmias, or a history of unexplained syncope (excluding cases caused by vasovagal reactions or dehydration).
  4. History of severe non-ischemic cardiomyopathy.
* Has an active or uncontrolled infection requiring systemic treatment within 1 week prior to screening.
* Has Grade 2-4 acute GVHD or moderate-to-severe chronic GVHD within 4 weeks prior to screening.
* Has experienced a cerebrovascular accident or seizure within 6 months prior to screening.
* Has experienced a deep vein thrombosis or arterial embolism event within 6 months prior to screening.
* Has a history of other malignancies except for: tumors with no evidence of active disease where treatment was completed \>2 years ago; adequately treated carcinoma in situ of the cervix; basal cell or squamous cell skin cancer; radical prostatectomy; radical ductal carcinoma in situ.
* Received a live attenuated vaccine within 4 weeks prior to screening.
* Any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in this study.

Where this trial is running

Wuhan, Hubei

• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Jia Wei

Conditions Non-Hodgkin Lymphoma; CAR-T; CD19; in vivo