This Phase I/II study evaluates the safety, tolerability, and efficacy of N-3C01 administered subcutaneously, both as monotherapy and in combination with a PD-(L)1 monoclonal antibody, in patients with advanced solid tumors. Phase I involves dose escalation for both monotherapy and combination therapy, while Phase II includes cohort expansion for the combination therapy.
This is a Phase I/II clinical study designed to evaluate the safety, tolerability, and efficacy of N-3C01 administered subcutaneously, both as monotherapy and in combination with a PD-(L)1 monoclonal antibody, in patients with advanced solid tumors. Phase I consists of dose escalation of N-3C01 as monotherapy and in combination with PD-(L)1 antibody, while Phase II involves cohort expansion of the combination therapy. The Phase I study employs an escalation design. Participants will receive N-3C01 either as monotherapy or in combination with a fixed dose of PD-(L)1 monoclonal antibody. The study will assess safety, tolerability, and pharmacokinetics across different dose levels and dosing schedules to determine the maximum tolerated dose and the recommended Phase II dose (RP2D). A Safety Review Committee (SRC), comprising the Investigator, Sponsor representative, and Medical Monitor, will oversee safety evaluations. The SRC will review dose-limiting toxicity data and provide recommendations on dose escalation, de-escalation, expansion, or study discontinuation and RP2D. In Phase II, eligible participants will receive N-3C01 at the RP2D in combination with a fixed dose of PD-(L)1 monoclonal antibody.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
114
subcutaneous injection once every 2 weeks
subcutaneous injection once every 3 weeks
subcutaneous injection once every 2 or 3 weeks.
GenesisCare Research
Saint Leonards, New South Wales, Australia
NOT_YET_RECRUITINGSan Clinical Trials Unit
Wahroonga, New South Wales, Australia
NOT_YET_RECRUITINGCorner Edith & Platt Streets, , NSW 2298 Australia
Waratah, New South Wales, Australia
Number of participants with dose-limiting toxicity (DLT)
All DLTs will be coded using the MedDRA® version 29.0 or higher by System Organ Class and Preferred Term, and graded according to CTCAE 6.0. The number and incidence of DLTs will be calculated and summarized by treatment group.
Time frame: 28 days from the first study dose
Number of participants with adverse enents (AE), serious adverse events (SAEs), treatment-emergent AEs (TEAEs)
All AEs will be coded using the MedDRA® version 29.0 or higher and graded according to CTCAE 6.0. emphasis will be placed on TEAE. Summary tables will include the number of participants (n), frequency, and percentage (%).
Time frame: From screening to safety follow-up , up to approximately 24 months
Number of participants with abnormality in vital signs
Vital signs measurements will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). Clinical significant changes shift from baseline will also be presented using the classification 'Normal', 'Abnormal, Not clinically significant', 'Abnormal, clinically significant'.
Time frame: From screening to safety follow-up , up to approximately 24 months
Number of participants with abnormality in ECG parameters
ECG measurements will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). Clinical significant changes shift from baseline will also be presented using the classification 'Normal', 'Abnormal, Not clinically significant', 'Abnormal, clinically significant'.
Time frame: From screening to safety follow-up , up to approximately 24 months
Number of participants with abnormality in hematology assessments
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intravenous injection once every 3 weeks
Hunan Cancer Hospital
Changsha, Hunan, China
NOT_YET_RECRUITINGShanghai East Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Zhengzhou, China
NOT_YET_RECRUITINGFor each parameter, summaries will be presented for the baseline and each scheduled post-baseline visit. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). Clinical significant changes shift from baseline will also be presented using the classification 'Normal', 'Abnormal, Not clinically significant', 'Abnormal, clinically significant'.
Time frame: From screening to safety follow-up , up to approximately 24 months
Number of participants with abnormality in blood chemistry parameters
For each parameter, summaries will be presented for the baseline and each scheduled post-baseline visit. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). Clinical significant changes shift from baseline will also be presented using the classification 'Normal', 'Abnormal, Not clinically significant', 'Abnormal, clinically significant'.
Time frame: From screening to safety follow-up , up to approximately 24 months
Number of participants with abnormality in coagulation parameters
Each measurement will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). Clinical significant changes shift from baseline will also be presented using the classification 'Normal', 'Abnormal, Not clinically significant', 'Abnormal, clinically significant'.
Time frame: From screening to safety follow-up , up to approximately 24 months
Number of participants with abnormality in routine urinalysis parameters
The urinalysis table will present clinically significant for the reported results at baseline and each post-baseline visit for all parameters (categorical descriptive analysis).
Time frame: From screening to safety follow-up , up to approximately 24 months
Number of participants with abnormality in thyroid function parameters
For each parameter, summaries will be presented for the baseline and each scheduled post-baseline visit. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). Clinical significant changes shift from baseline will also be presented using the classification 'Normal', 'Abnormal, Not clinically significant', 'Abnormal, clinically significant'.
Time frame: From screening to safety follow-up , up to approximately 24 months
Maximum concentration (Cmax)
Maximum plasma drug concentration obtained directly from the plasma concentration time profiles.
Time frame: From start of treatment to end of treatment, up to approximately 24 months
Area under the curve (AUC)
AUC will be determined when appropriate. Analyses will be performed on the plasma PKPS using the actual sampling times.
Time frame: From start of treatment to end of treatment, up to approximately 24 months.
Tmax
Time to maximum observed plasma drug concentration.
Time frame: From start of treatment to end of treatment, up to approximately 24 months
Clearance (CL)
Apparent total plasma clearance will be determined when appropriate.
Time frame: From start of treatment to end of treatment, up to approximately 24 months
half-life (t1/2)
t1/2 will be determined when appropriate.
Time frame: From start of treatment to end of treatment, up to approximately 24 months.
Volume of distribution (V)
Volume of distribution will be determined when appropriate.
Time frame: From start of treatment to end of treatment, up to approximately 24 months
The incidence of ADA and NAb of N-3C01
The number and percentage of positive participants with anti-drug antibodies will be summarized. All immunogenicity data will also be presented in a by-participant data listing.
Time frame: From start of treatment to end of treatment, up to approximately 24 months
Objective response rate (ORR)
ORR is defined as the percentage of participants with a best overall response of CR or PR according to RECIST v1.1.
Time frame: From start of treatment to end of treatment, up to approximately 24 months
Disease control rate (DCR)
DCR is defined as the percentage of participants with a best overall response of CR, PR or SD accoding to RECIST v1.1.
Time frame: From start of treatment to end of treatment, up to approximately 24 months
Duration of response (DoR)
For participants who achieve a confirmed response (CR or PR), Duration of Response is defined as the time from the first date of response until disease progression or death, whichever occurs first.
Time frame: From start of treatment to end of treatment, up to approximately 24 months.
Progression-Free Survival (PFS)
PFS is defined as the time from the first dose of N-3C01 to the first occurrence of disease progression (radiographic) or death, whichever occurs first. In progression-free patients, PFS will be censored at the time of the last evaluable tumor assessment.
Time frame: From start of treatment to safety follow-up, up to approximately 24 months
Overall Survival (OS)
OS is defined as the time from the first dose of N-3C01 to participant death. Patients alive or lost to follow-up will be censored at the last date known to be alive.
Time frame: From start of treatment to end of treatment, up to approximately 24 months