A Phase I Study of BC3402 as a Single Agent in Patients With MDS and CMML

NCT05690425 | Unknown Phase 1

• 1 other identifier: BC3402-002
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study to evaluate the safety ,Tolerability, PK, PD, and preliminary efficacy of BC3402 Monotherapy in MDS or CMML, and explore the RP2D/MTD dose. The patients with very low,low,intermediate,or high,very high risk of MDS or CMML,who meet the criteria will receive BC3402 as a single agent via intravenous infusion Q3W , Up to 3 dose cohorts will be sequentially enrolled using an accelerated titration combined with a "3+3 design" approach.Dose limiting toxicities (DLT) will be assessed during the first cycles (i.e., total 3 weeks). A Safety Monitoring Committee (SMC), comprised of the Sponsor's medical representatives, safety physician, and the principal investigator (PI), will be established for the determination of dose levels to be administered and dose regimen during dose escalation based on the data available from the previous dose levels. Additional dose levels may be explored based on the emerging safety, PK, and PD data during the study.

Conditions

Hematologic Malignancy

Keywords

MDS and CMML

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicities(DLTs) within 28 days (first cycle)

  The DLT for this study will be evaluated in the first cycle. The DLT will include any of the following adverse events that cannot be clearly attributed to other reasons and are judged to be related to BC3402. 1. Hematologic toxicity in the following cases: Hematologic toxicity ≥ grade 4 occurred in the first cycle, which could not be recovered to baseline value within 21 days after the occurrence, and bone marrow primordial cells\<5%. 2. Non hematologic toxicities: * Grade 2 above ALT and/or AST elevational concomitant grade 2 total bilirubin elevation(non biliary obstruction or other reasons); * QTcF interval \> 470 ms or longer than baseline \> 60 ms; * Grade 3 or above non-haematological toxicity; 3. Others Any ongoing toxicity (of any grade) not caused by disease progression that results in a delay of more than 2 weeks in the next scheduled cycle;

  Dose limiting toxicities (DLT) will be assessed during the first cycle (i.e., total 3 weeks).

Study Arms (1)

BC3402 treatment group

EXPERIMENTAL

BC3402 as a single agent via intravenous infusion once every 3-weeks

Drug: BC3402 Injection

Interventions

BC3402 Injection DRUG

Subjects will receive BC3402 as a single agent via intravenous infusion once every 3-weeks (Q3W),the dose of BC3402 was calculated according to the dose group and body weight of the subjects.

Also known as: not have

BC3402 treatment group

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 be able to understand and voluntarily sign the informed consent form;
• Subjects were 18 years old or above when they signed the informed consent form;
• Subjects mast be willing to undergo serial bone marrow aspirate procedures on the study;
• Morphologically confirmed diagnosis as extremely low risk, low risk, intermediate risk, high risk, extremely high risk MDS (IPSS-R classification) or CMML according to WHO (2016) diagnostic criteria, and WBC\<13\* 10\^9/L (allowed to receive hydroxyurea or leukocyte removal before enrollment to reduce WBC count), and:
• According to IPSS-R, patients diagnosis as extremely low risk, low risk or intermediate risk MDS must meet one or more of the following criteria:
• Patients who are RBCs and/or platelets transfusion-dependent , must receive stable infusion 2U/month above for 3 months before the first dose;
• Patients who are RBCs transfusion-dependent must Erythropoiesis stimulating agents (ESAs) failure or intolerant ;
• Patients who are RBCs transfusion-dependent without ESA treatment mast have serum erythropoietin level \>500 U/L ;
• MDS patients with isolated del (5q) ("5q syndrome") must have disease progression or intolerance during lenalidomide treatment;
• Platelet transfusion dependent patients must be treated with thrombopoietin receptor agonist (TPO-RA) for relapse/refractory or intolerance;
• Persistent (\>3 months) neutrophil absolute count is lower than 1.5 before screening × 10\^9/L；
• MDS and CMML patients rated as high-risk or extremely high-risk according to IPSS-R:
• The monotherapy of demethylated drugs (HMA) failed (4 cycles of decitabine treatment or 6 cycles of azacytidine treatment) or was not tolerated;
• Not suitable for intensive treatment;
• CMML patients must fail or not tolerate at least one previous treatment (including but not limited to hydroxyurea treatment, HMA treatment, etc.);

You may not qualify if:

• Suitable and willing to accept hematopoietic stem cell transplantation (allogeneic or autologous);
• Immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., were used within 2 weeks before the first use of the test drug;
• \. Prior treatment with immunomodulatory agents including but not limited to thymosin, interleukin-2, and interferon within 2 weeks prior to the first dose of study drugs.
• Patients who have used any Chinese herbal medicine or traditional Chinese medicine with anti-tumor activity within 2 weeks prior to the first dose of study drugs.
• Patients who received live attenuated vaccine within 4 weeks prior to the first dose of study drug.
• Prior treatment with an investigational drug within 4 weeks or 5 half-lives of the agent (whichever is longer) before the planned first dose of study drug. The washout period for biologic agents should be 28 days since the last dose.
• Prior exposure to TIM-3 targeted therapy at any time.
• Participants receiving chemotherapy within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment;
• Major organ surgery or significant trauma or radiotherapy within 2 weeks before entering the study;
• Have received systemic glucocorticoid (prednisone\>10mg/day or equivalent dose of the same drug) or other immunosuppressive drugs within 2 weeks before the first use of the study drug;
• Active infections or other severe infections requiring systemic antibiotics, antiviral or antifungal drugs within 2 weeks before the first administration of the study treatment. Except for those who are treated with anti infection prevention according to local guidelines or the judgment of the researcher.
• Active hepatitis B or C, history of HIV infection, active syphilis;
• Patients with autoimmune diseases;
• Known uncontrolled central nervous system (CNS) involvement;
• Patients with history of serious cardiovascular and cerebrovascular diseases, including but not limited to, (1)Serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, Ⅱ - Ⅲ degree atrioventricular block ect.

Sponsors & Collaborators

• Biocity Biopharmaceutics Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Jinan University

Guangzhou, Guangdong, 510630, China

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• hui zeng, prof

  First Affiliated Hospital of Jinan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

hui zeng, prof

CONTACT

18002201919; xyzengh@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: January 19, 2023
• Study Start: July 6, 2023
• Primary Completion: March 15, 2024
• Study Completion: June 15, 2024
• Last Updated: July 24, 2023

Record last verified: 2023-07

Locations

CN (1)