A Phase I/II Study of TRS005 in Combination With Cyclophosphamide, Doxorubicin, and Prednisone（T-CHP） in Previously Untreated Patients With CD20-positive DLBCL

Official title

A Phase I/II Study Evaluating the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of TRS005 in Combination With Cyclophosphamide, Doxorubicin, and Prednisone（T-CHP） in Previously Untreated Patients With CD20-positive DLBCL

Overview

This trial is a multicenter, open-label, single-arm, dose-escalation and dose-expansion clinical trial. The dose was increased according to the "3 + 3" rule. Patients with previously untreated patients with CD20-positive DLBCL were selected to evaluate the safety, tolerance (DLT, MTD), pharmacokinetics, and anti-tumor activity of TRS005 in combination with standard doses of cyclophosphamide, doxorubicin, and prednisone（T-CHP） by intravenous drip every 3 weeks.

Interventions

• Drug TRS005
  TRS005 will be administered at a starting dose of 0.8mg/kg IV every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles (up to 8).
• Drug Cyclophosphamide
  Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m\^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.
• Drug Doxorubicin
  Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.
• Drug Prednisolone
  Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.

Primary outcome measures

• Part I: Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD) [Time frame: Cycle 1 Day 1 (C1D1) to Cycle 1 Day 21 (C1D21)]
• Part I and II: Adverse Events [Time frame: Day 1 up to approximately 6 months]

Secondary outcome measures (6)

• Overall Response Rate (ORR) [Time frame: At the end of treatment (Month 6)]
• Duration of Response (DOR) [Time frame: Up to 24 months]
• Progression-Free Survival (PFS) [Time frame: Up to 24 months]
• Overall Survival (OS) [Time frame: Up to 24 months]
• Immunogenicity [Time frame: At the end of treatment (Month 6)]
• Serum concentration [Time frame: At the end of cycle 4 (each cycle is 21 days)]

Eligibility criteria

Inclusion criteria

• 1\. Part I: Age 18 -65 years old; Part II: Aged ≥ 18 years old, both male and female.
• 2\. Previously untreated patients with CD20-positive DLBCL diagnoses by 2022 WHO.
• 3\. Measurable disease of at least 15mm (node)/10mm (extranodal).
• 4\. ECOG performance status 0-2.
• 5\. International Prognostic Index (IPI) score of 2-5.
• 6\. Estimated survival time ≥6 months.
• 7\. Having sufficient organ function.
• 8\. Female and male patients of childbearing age and their spouses are willing to carry out adequate contraception throughout the study period, and female patients of childbearing age must have negative serum pregnancy test within 7 days before the first administration.
• 9\. Patients voluntarily agree to participate in the study and to sign the informed consent form.

Exclusion criteria

• 1\. Contraindication to any of the individual components of study drugs, including prior receipt of xenoproteins, biological agents.
• 2\. Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load; Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load; Human immunodeficiency virus (HIV) seropositive.
• 3\. Clinically apparent central nervous system (CNS) lymphoma.
• 4\. Patient has ≥ Grade 2 peripheral neuropathy.
• 5\. Investigator-assessed diabetes uncontrolled by drug therapy.
• 6\. Clinically significant third space fluid accumulation.
• 7\. Patients with other malignancies within the past 5 years.
• 8\. With active autoimmune diseases.
• 9\. Accompanied by serious cardiovascular diseases.
• 10\. Accompanied by serious diseases and serious active infections.
• 11\. The dosage of steroid hormone (prednisone phase equivalent) used greater than 20mg/ day within 28 days prior to first administration for more than 14 consecutive days, or immunosuppressive treatment.
• 12\. Various vaccines were inoculated within 28 days prior to first administration;
• 13\. Major surgery (except diagnostic biopsy) within 28 days prior to first administration or during the study period.
• 14\. Participate in clinical trials of other drugs or medical devices within 28 days prior to first administration.
• 15\. Serious medical or psychiatric illness likely to interfere with participation in this study.
• 16\. Investigators assessed as unsuitable to participate in this study for other reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Chinese Academy of Medical Sciences, Cancer Hospital — Beijing

Identifiers

NCT: NCT07035379 · TRS00501003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗