An Exploratory Clinical Study of RD133 in Subjects With Relapsed or Refractory MSLN-Positive Solid Tumors

NCT05166070 | Recruiting Early Phase 1

• 1 other identifier: RD133CI002
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center exploratory clinical trial. It is estimated that 9-24 subjects will be enrolled. The "3+3" dose escalation design is adopted. The main purpose is to evaluate the safety of RD133 in the treatment of subjects with relapsed or refractory MSLN-positive solid tumors and explore the Recommend phase II dose of RD133 in the treatment of patients with relapsed/refractory MSLN-positive solid tumors.

Conditions

Solid Tumor

Keywords

mesothelin-positive solid tumor; CAR-T

Outcome Measures

Primary Outcomes (2)

• Type and incidence of dose-limiting toxicity (DLT) by dose group

  The number and percentage of DLT in each dose group

  2 years post infusion

• Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group

  Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity.

  2 years post infusion

Secondary Outcomes (9)

• Number of Participants With Adverse Events

  2 years post infusion

• Objective response rate (ORR)

  2 years post infusion

• Duration of response (DoR)

  2 years post infusion

• Time to response (TTR)

  2 years post infusion

• Disease control rate (DCR)

  2 years post infusion

Other Outcomes (8)

• Concentrations of TGF-β

  2 years post infusion

• Expression of biomarker in tumor tissue

  2 years post infusion

• Immunogenicity of RD133

  2 years post infusion

Study Arms (1)

Administration of RD133

EXPERIMENTAL

Three dose groups of 1.0×10\^6 CAR-T/kg, 3.0×10\^6 CAR-T/kg, and 6.0×10\^6 CAR-T/kg RD133 are designed in this study. 3 to 6 subjects are expected to be enrolled in each dose group according to observed DLT. RD133 will be intravenously infused at least 24 hours after lymphodepletion preconditioning. According to the assigned dose group, the designated dose of RD133 will be infused in a single infusion within 30 minutes on day 0.

Drug: RD133

Interventions

RD133 DRUG

The enhanced MSLN-CAR-T cell design of this study is obtained by co-infecting T cells with two lentiviral vectors. One lentiviral vector expresses CD19-CAR and tEGFR molecular safety switch, and the other lentiviral vector expresses MSLN- CAR and dnTGFβRII receptors. dnTGFβRII receptor without intracellular signal is used to resist the inhibition of T cell function by the immune microenvironment of tumor tissue. In addition, for the safety of CAR-T cell application in vivo, tEGFR is used in the CAR design as a molecular safety switch for CAR-T cells.

Administration of RD133

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must personally sign the written informed consent form approved by the ethics committee before the start of the study;
• ≥18 years of age;
• Have received at least 2 prior standard treatments, and achieved no response to the last-line treatment;
• \>25% Mesothelin positive rate on tumor cell membrane confirmed by prior immunohistochemistry of tumor tissue or freshly punctured tissue;
• Expected survival ≥ 12 weeks;
• ECOG score ≤ 2;
• At least one measurable target lesion that meets the RECIST v1.1 standard;
• Female or male subjects with fertility should agree to practice an effective method of contraception from the day of signing the ICF until 365 days after the infusion. Effective method of contraception is defined as: abstinence or contraceptive methods with an annual failure rate of \<1% specified in the plan. ；
• Before being enrolled in the group, the subject must have proper organ function and meet all of the following criteria:
• The absolute value of neutrophils≥1.0×10\^9/L (granulocyte colony stimulating factor (G-CSF) support is allowed, but must be without supportive treatment within 7 days before the examination); 9.2 Platelet count ≥75×10\^9/L (must be without blood transfusion support \[including blood component transfusion\] or thrombopoietin \[TPO\], or other treatments for the purpose of increasing platelets within 7 days before the examination); 9.3 Hemoglobin ≥9 g/dl (must be without blood transfusion support \[including blood component transfusion\] within 7 days before the examination); 9.4 Bilirubin value ≤1.5×upper limit of normal (ULN) (except bile duct obstruction caused by tumor compression); 9.5 Creatinine clearance rate ≥60 ml/min; 9.6 ALT or AST ≤2.5×upper limit of normal (ULN) (with liver involvement ≤5×ULN); 9.7 The results of echocardiography indicate that the cardiac ejection fraction is ≥ 50%, without obvious pericardial effusion; 9.8 Stable coagulation function: INR ≤ 1.5, APTT ≤1.2×ULN (except tumor-related anticoagulation therapy); 9.9 \>91% basic blood oxygen saturation in the natural indoor air environments.

You may not qualify if:

• Subject who has received any of the following prior treatments:
• Subject with acute or chronic graft-versus-host disease (GVHD) who need systemic treatment within 4 weeks before enrollment; 1.2 Subject who has received gene therapy before enrollment; 1.3 Subject who needs systematic immunosuppressive therapy (except topical drugs) to control autoimmune diseases (eg: Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.), immunodeficiency or other diseases in the first 2 years after enrollment; 1.4 Subject who has been injected with live vaccines within 4 weeks before enrollment; 1.5 Subject has received other interventional clinical research drugs within 12 weeks before apheresis.
• Subject with central metastasis or complete intestinal obstruction;
• Subject with moderate or more severe hydrothorax and ascites which are hard to control by conventional treatment and require continuous catheter drainage;
• With an active malignant tumor in the past 5 years, unless it is a curable tumor and has been obviously cured, such as basal or squamous cell carcinoma, cervical or breast carcinoma in situ, etc.
• Subject with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and abnormal HBV DNA test results in peripheral blood (abnormal HBV DNA test results are defined as: HBV DNA quantitative level higher than the lower limit of the detection center or higher than normal range of the detection center; or qualitative HBV DNA test positive); Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) antibody positive; Cytomegalovirus ( CMV) DNA test positive; syphilis test RPR positive.
• With an uncontrollable active infection (except genitourinary system infection and upper respiratory tract infection \<CTCAE Grade 2).
• Severe heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 3), severe arrhythmia.
• Subject with hypertension that cannot be controlled by medication.
• The toxicity of previous treatment has not been relieved to baseline or ≤1 (NCI-CTCAE v5.0, except for hair loss and laboratory abnormalities without clinical significance).
• Major surgery within 2 weeks before enrollment, or has surgery planned during the time the subject is expected to be infused with RD133 or within 12 weeks after RD133 infusion (except planned surgery under local anesthesia).
• Subject who has a solid organ transplant.
• Women who are pregnant or breastfeeding.
• Subject with previous central nervous system diseases (such as cerebral aneurysm, epilepsy, stroke, Alzheimer's disease, mental illness, etc.) or mental disorders.
• Other unstable systemic diseases judged by the investigator: including but not limited to severe liver, kidney, or metabolic diseases that require medication.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Shanghai IASO Biotechnology Co., Ltd: collaborator

Study Sites (1)

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

Study Officials

• Lingxiang Liu

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lingxiang Liu

CONTACT

llxlau@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Model Details: The study is a single center, open label, non-controlled, exploratory study. The "3+3"dose escalation design will be implemented to evaluate the safety and tolerability of RD133 in the treatment of subjects with relapsed/refractory MSLN-positive solid tumors.

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: December 21, 2021
• Study Start: January 1, 2022
• Primary Completion: January 1, 2024
• Study Completion (Estimated): January 1, 2037
• Last Updated: December 21, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)