An Open-Label, Multi-center, Phase I/II Study of CN202 in Adult Subjects With Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies
Overview
- Phase
- Phase 1
- Intervention
- CN202
- Conditions
- Locally Advanced Solid Tumor
- Sponsor
- Curon Biopharmaceutical (Australia) Co Pty Ltd
- Enrollment
- 164
- Primary Endpoint
- To identify a recommended Phase II dose (RP2D) of CN202
- Last Updated
- 4 years ago
Overview
Brief Summary
The study is designed to evaluate the safety, tolerability, pharmacokinetic characteristics and anti-tumor activity of CN202 in adult subjects with locally advanced or metastatic solid tumor or hematologic malignancies
Detailed Description
This is a multi-centre, open-label, Phase I/II study in adult subjects with locally advanced or metastatic solid tumor or hematologic malignancies. The study consists of three parts Phase Ia: Dose Escalation: This is a dose escalation for assessment of dose-limiting toxicities (DLT) at approximately four dose levels in subjects with locally advanced or metastatic solid tumor or hematologic malignancies. Phase Ib: Dose Expansion: To evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of CN202, prior to determination of Maximum tolerated dose (MTD) Phase II: To further evaluate the safety, tolerance, pharmacokinetic characteristics, and anti-tumor activity of CN202 in subjects with select tumors. All subjects will receive the recommended Phase II dose of CN202. There will be 13 to 24 subjects enrolled in phase Ia, 12 to 40 subjects in phase Ib and 15 to 100 subjects in phase II
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects ≥ age of 18 on the day of signing informed consent;
- •Histologically or cytologically diagnosed metastatic or locally advanced solid tumor or hematologic malignancy (unresectable), for whom no effective standard anti-tumor therapy existed or in the opinion of the Investigator have been considered ineligible for standard anti-tumor therapy at this stage, or are intolerant to standard anti-tumor therapy, or standard therapy had failed or the subject has refused standard anti-tumor therapy, or recurrent and progressing since last line anti-tumor therapy;
- •Representative tumor specimens in paraffin blocks (preferred) or at least 10 unstained slides, with an associated pathology report, requested at any time prior to study entry. Only tissue from core needle, punch, or excisional biopsy sample collection will be accepted. If archival tissue is insufficient or unavailable, the subjects may still be eligible upon discussion with Medical Monitor and approved by sponsor.
- •At least 1evaluable tumor lesion per RECIST v1.1 (Solid Tumors) and Lugano 2014 Criteria (Lymphoma). Disease-specific criteria will be used for prostate cancer and or other tumors. The subjects enrolled in phase Ib/II study must have measurable disease.
- •Subjects with Eastern Cooperative Oncology Group (ECOG) performance score of 0 to1;
- •At least 3 months of expected survival;
- •Female subjects must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception method from Screening until the end of the Safety Follow-up period, 90 (±7 days) days after the last dose of the study drug. Double contraception is defined as a condom AND one other from of the following:
- •Established hormonal contraception (with approved OCPs, long-acting implantable hormones, injectable hormones);
- •A vaginal ring or an intrauterine device (IUD);
- •Documented evidence of surgical sterilization at least 6 months prior to screening (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy for women or vasectomy for men \[with appropriate post-vasectomy documentation of the absence of sperm in semen\] provided the male partner is a sole partner).
Exclusion Criteria
- •Received anti-tumor therapy, including radiotherapy, chemotherapy, hormonal therapy, immunotherapy, within 3 weeks prior to initiation of study treatment, however, the following are allowed:
- •Palliative radiation therapy \> 2 weeks.
- •Small molecule targeted therapy \> 2 weeks. But subject who has had anti-EGFR or anti-TKI (egerlotinib, gefitinib, afatinib, or crizotinib) \> 1 week prior to the first dose of study therapy.
- •Use of immunomodulatory drugs \> 14 days or 5 half-lives of the drug prior to the first dose of study drug (whichever is shorter), including but not limited to thymosin, interleukin-2 (IL-2), interferon (IFN), etc.
- •Herbal therapy \> 1 week.
- •Hormone-replacement therapy or oral contraceptives.
- •Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer.
- •The subjects had prior treatment with anti-PD-L1 or anti-PD-1 therapeutic antibody, with the following exceptions:
- •The subjects can be enrolled in Phase Ia study if no history of severe immune-related adverse effects from checkpoint inhibitor treatment or any that has led to discontinuation (CTCAE Grade 3 and 4).
- •The subjects may be enrolled in Phase Ib/II study if the following requirements are met:
Arms & Interventions
Single Arm
Four planned CN202 dose level of 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg Subjects will receive CN202 by intravenous infusion (IV) on Day 1 of each cycle (once every 2 weeks) for up to 24 months
Intervention: CN202
Outcomes
Primary Outcomes
To identify a recommended Phase II dose (RP2D) of CN202
Time Frame: Baseline to End of the Treatment assessed up to an average of 24 months
The recommended Phase II dose (RP2D) will be determined based on safety, efficacy, pharmacokinetics and pharmacodynamic date of CN202
To evaluate the safety and tolerability of CN202 administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies through adverse events as assessed by NCI-CTCAE v5.0
Time Frame: Measurements at Baseline till 90 days after the last dose of study drug
Number of participants with treatment related adverse events as assessed by NCI-CTCAE v5.0
To evaluate the dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) of CN202 when administered as a single-agent to subjects
Time Frame: DLT assessed within 21 days after the first dose of CN202
Measured by Incidence of dose limiting toxicities (DLT) during the first cycle of treatment and DLT observation period
To evaluate the anti-tumor activity of CN202 in selected solid tumors or hematologic malignancies as determined by Objective Response Rate (ORR)
Time Frame: Baseline to End of the Treatment assessed up to an average of 24 months
Measured/determined by Objective Response Rate
Secondary Outcomes
- To evaluate the safety and tolerability of CN202 administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies through vital signs as assessed by pulse, systolic blood pressure, and diastolic blood pressure(Baseline to End of the Treatment assessed up to an average of 24 months)
- To assess the immunogenic potential of CN202 by measuring anti-CN202 antibodies through Immunogenicity analysis test results(Baseline to End of the Treatment assessed up to an average of 24 months)
- To assess the pharmacodynamic (PD) of CN202 when administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies(Baseline to End of the Treatment assessed up to an average of 24 months)
- To evaluate the safety and tolerability of CN202 administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies through Electrocardiogram (ECG)(Baseline to End of the Treatment assessed up to an average of 24 months)
- To evaluate the safety and tolerability of CN202 administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies through vital signs as assessed by heart rate(Baseline to End of the Treatment assessed up to an average of 24 months)
- To evaluate the safety and tolerability of CN202 administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies through vital signs as assessed by respiratory rate(Baseline to End of the Treatment assessed up to an average of 24 months)
- To evaluate the safety and tolerability of CN202 administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies through vital signs as assessed by body temperature(Baseline to End of the Treatment assessed up to an average of 24 months)
- To evaluate the pharmacokinetic (PK) of CN202 when administered to subjects with locally advanced or metastatic solid tumor or hematologic malignancies(Baseline to End of the Treatment assessed up to an average of 24 months)