Clinical trial NCT04418141: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN1
Official title: A Phase I, Open Label, Multi-Center, Dose Escalation Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN1 in Patients With Advanced Solid Tumors or B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
B Cell Lymphoma
Lead sponsor: Curon Biopharmaceutical (Australia) Co Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2020-06-05
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is the first-in-human clinical trial of CN1 to evaluate the safety, tolerability, pharmacokinetic (PK) profile and preliminary efficacy of CN1 in patients with advanced solid tumors or B-cell lymphoma. This study will provide a basis for further clinical development of CN1.

Detailed description: CN1 could promote T cell activation and cytokine secretion, thereby enhancing the function of CD4+ and CD8+ T cells, and could also regulate Treg cells, thus CN1 is considered to enhance the anti-tumor immune response and have potential antitumor activity.

In this multicenter, open-label, dose-escalation Phase I study six dose levels are planned. Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). After completion of treatment cycles, the participant will be assessed by the Principal Investigator and/or Safety Monitoring Committee (SMC).

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years old, male or female;
2. Subjects with histologically or cytologically diagnosed advanced malignant solid tumors or B-cell lymphoma who have failed on, or are intolerant to, standard therapy, for whom there are no standard of care regimens, or who are otherwise not eligible for standard therapy at this stage;
3. Subjects with Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;
4. Females must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception from screening until the end of the follow-up period.
5. Subjects must be able to understand and sign the paper informed consent before any study specific procedure.

Exclusion Criteria:

1. Received anti-tumor treatment such as radiotherapy, chemotherapy, biotherapy, endocrine therapy, immunotherapy, etc., within 4 weeks prior to the first dose of study drug.
2. Received other investigational agents (not yet approved by any regulatory agency) within 4 weeks prior to the first dose of study drug;
3. Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks prior to the first dose of study drug;
4. Systemic application of corticosteroids (prednisone \> 10 mg/day or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of study drug;

   * Exceptions: topical, ocular, intra-articular, intranasal, and inhaled corticosteroids, or short-term corticosteroids for prophylaxis (e.g., contrast allergy prophylaxis).
5. Use of live attenuated vaccine within 4 weeks prior to the first dose of study drug;
6. Clinically symptomatic metastases to the central nervous system or meninges, or other evidence of uncontrolled metastases to the central nervous system or meninges of the subject;
7. Active infection and in current need of, or likely to need, intravenous anti-infective therapy;
8. History of immunodeficiency, including history of any positive test result for human immunodeficiency virus (HIV) antibody;
9. Active hepatitis B or hepatitis C virus infection.
10. Subjects with active or previous autoimmune diseases (e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except subjects with clinically stable autoimmune thyroid disease;
11. Subjects with mental disorders or other conditions that pose high non-compliance risks in the opinion of the investigator;

Primary outcomes:
measure: To determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and/or recommended Phase II dose (RP2D) of CN1 administered to patients with advanced solid tumor or B-cell lymphoma.
timeFrame: 21 Days after the first dose i.e. starting dose level 0.03 mg/kg
Secondary outcomes:
measure: To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Physical Exam
timeFrame: From baseline(Week 1) to 90 days after the last dose
measure: To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Adverse Events/Serious Adverse Events
timeFrame: From baseline(Week 1) to 90 days after the last dose
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Area under the plasma concentration-time curve
timeFrame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Tmax
timeFrame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Apparent volume of distribution at steady state
timeFrame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Accumulation factor based on AUC 0-τ
timeFrame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
measure: To assess the immunogenicity to CN1 in patients with advanced solid tumor or B-cell lymphoma through ADA testing
timeFrame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
measure: To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through ORR analysis
timeFrame: Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.
measure: To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DCR analysis.
timeFrame: Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.
measure: To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DoR analysis.
timeFrame: Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.
Other outcomes:
Locations:
city: Brisbane
country: Austria
facility: Mater Medical Centre
state: Queensland
Study officials:
affiliation: Macquarie University Hospital
name: John Park
role: PRINCIPAL_INVESTIGATOR
affiliation: Icon Cancer Centre (Brisbane)
name: Jim Coward
role: PRINCIPAL_INVESTIGATOR
affiliation: Illawarra Cancer Care Centre (Wollongong)
name: Daniel Brungs
role: PRINCIPAL_INVESTIGATOR
affiliation: Cabrini Hospital (Melbourne)
name: Gary Richardson
role: PRINCIPAL_INVESTIGATOR
References: