A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN1

• ClinicalTrials.gov Identifier: NCT04418141
• Recruitment Status: Recruiting
• First Posted: June 5, 2020
• Last Update Posted: July 28, 2020
• Sponsor: Curon Biopharmaceutical (Australia) Co Pty Ltd
• Collaborator: Novotech (Australia) Pty Limited
• Information provided by (Responsible Party): Curon Biopharmaceutical (Australia) Co Pty Ltd

Tracking Information

• First Submitted Date: May 13, 2020
• First Posted Date: June 5, 2020
• Last Update Posted Date: July 28, 2020
• Actual Study Start Date: July 2, 2020
• Estimated Primary Completion Date: February 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 3, 2020)

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. [ Time Frame: 21 Days after the first dose i.e. starting dose level 0.03 mg/kg ]

DLT is measured in the observation period of 21 days after the first dose i.e. starting dose level 0.03 mg/kg. if the enrolled subject does not experience a study drug related Grade 2 or higher adverse event (AE) per NCI-Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, the subject will start to receive the next designated dose level of 0.3 mg/kg in the second 21 days dosing cycle.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 3, 2020)

• To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Physical Exam [ Time Frame: From baseline(Week 1) to 90 days after the last dose ]
  Measured by incidence of abnormal physical examination findings.
• To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Adverse Events/Serious Adverse Events [ Time Frame: From baseline(Week 1) to 90 days after the last dose ]
  Measured by incidence of Adverse Events/Serious Adverse Events. All AEs will be summarized according to the Medical Dictionary for Regulatory Activities (MedDRA) v23.0 or higher and the severity will be categorized by CTCAE v5.0. The summary of all AEs will be focused on the treatment-emergent adverse events (TEAEs). A TEAE is defined as any AE that starts after the first dose of study drug till 90 +/- 7 days after the last dose of study drug.
• 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 [ Time Frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. ]
  The following parameter is used for evaluation during PK assessments: Area under the plasma concentration-time curve (AUC0-t, AUC0- ∞, AUC0-τ)
• To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Tmax [ Time Frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. ]
  The following parameter is used for evaluation during PK assessments: Time to maximum (Tmax)
• 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 [ Time Frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. ]
  The following parameter is used for evaluation during PK assessments: Apparent volume of distribution at steady state (Vss)
• 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 [ Time Frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. ]
  The following parameter is used for evaluation during PK assessments: Accumulation factor based on AUC 0-τ (R AUC0-τ)
• To assess the immunogenicity to CN1 in patients with advanced solid tumor or B-cell lymphoma through ADA testing [ Time Frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. ]
  A validated analysis method will be used for detection of anti-drug antibodies (ADA).
• To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through ORR analysis [ Time Frame: 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. ]
  Assessed by the number of participants with objective response (ORR)
• To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DCR analysis. [ Time Frame: 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. ]
  Assessed by the number of participants with Disease Control (DCR)
• To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DoR analysis. [ Time Frame: 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. ]
  Assessed by the number of participants with Duration of Response (DoR)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Solid Tumor
• B Cell Lymphoma

Intervention

Drug: CN1

Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). The 5 planned dose levels are 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg.

Study Arms

Experimental: Single Arm

Five planned CN1 dose levels of 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Subjects will receive CN1 by intravenous infusion (IV) on Day 1 (D1) of each cycle (once every 3 weeks per cycle).

Intervention: Drug: CN1

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 3, 2020): 22
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2022
• Estimated Primary Completion Date: February 2022 (Final data collection date for primary outcome measure)

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;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Danny Zhu; +86 138-1074-9637; Danming.Zhu@curonbiopharma.com

• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT04418141
• Other Study ID Numbers: CN1-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Curon Biopharmaceutical (Australia) Co Pty Ltd
• Study Sponsor: Curon Biopharmaceutical (Australia) Co Pty Ltd
• Collaborators: Novotech (Australia) Pty Limited

Investigators

• Principal Investigator: John Park; Macquarie University Hospital
• Principal Investigator: Jim Coward; Icon Cancer Centre (Brisbane)
• Principal Investigator: Daniel Brungs; Illawarra Cancer Care Centre (Wollongong)
• Principal Investigator: Gary Richardson; Cabrini Hospital (Melbourne)

• PRS Account: Curon Biopharmaceutical (Australia) Co Pty Ltd
• Verification Date: July 2020