The goal of this clinical trial is to learn if N17350 works to treat advanced solid tumors in adults. It will also learn about the safety of N17350 and help determine the best dose to use in future studies. The main questions it aims to answer are: 1. Does N17350 cause tumors to shrink or stop growing in some participants with advanced solid tumors? 2. Are there any side effects for participants when taking N17350? 3. What is the safest dose of N17350 and the dose that should be used for further study? 4. Researchers will give N17350 directly into tumor lesions using a needle (intratumoral injection). This is an open-label study, meaning all participants will receive N17350 and there is no placebo. Participants will: 1. Receive injections of N17350 into tumor lesions every second week for 8 or 12 weeks 2. Visit the clinic regularly for checkups, blood tests, and monitoring for side effects 3. Have imaging scans (such as CT or MRI) to measure tumors and assess response 4. Provide blood samples and, when required, tumor samples to help researchers understand how N17350 affects the tumor and the immune system
This is a Phase 1/2 clinical study evaluating an investigational medicine called N17350 in adults with advanced solid tumors that have spread or cannot be removed by surgery and for which standard treatment options are no longer working, are not available, or are not appropriate. N17350 will be administered by injection directly into tumor lesions (intratumoral injection). Giving N17350 into the tumor is intended to deliver treatment to the cancer site and may help stimulate an immune response against the tumor. This is an open-label study, meaning all participants will receive N17350 and both participants and the study team will know the treatment being given. The study is designed to evaluate safety, identify an optimal dose, and look for early signs of anti-tumor activity. Study Parts The study includes two parts: Part 1: Dose Finding (Phase 1) Small groups of participants will receive different dose levels of N17350. The main purpose is to understand how safe N17350 is and to determine a dose that can be given safely and is suitable for further study. Safety information from participants will be reviewed as dose levels are increased or adjusted. Part 2: Dose Expansion (Phase 2) After a dose is selected from Part 1, additional participants will receive N17350 at that dose. This part is designed to better understand safety at the selected dose and to further evaluate how well N17350 may work in participants with advanced solid tumors. Depending on the study plan, expansion may include groups of participants with specific tumor types. Treatment and Visits Participants will receive N17350 injections into tumor lesions every second week for 8 or 12 weeks. Participants will attend clinic visits for treatment administration and ongoing monitoring. Throughout the study, participants will undergo safety evaluations, which may include: Review of side effects and other medical problems Physical examinations and vital signs Blood and urine tests Heart monitoring (such as ECG), if required Review of medications and overall health status Participants will also undergo evaluations to measure how their cancer responds to treatment, which may include: Imaging scans (such as CT or MRI) to measure tumors over time Clinical assessments of injected lesions and other tumor sites Biomarker and Research Samples The study may include collection of blood samples and, when required, tumor samples to help researchers understand how N17350 affects the tumor and the immune system. These samples may be used to study markers of immune activation and other biological changes that could be associated with response or side effects. Outcomes and Goals The main goals of the study are to: Determine the type and frequency of side effects and evaluate overall safety Identify a recommended dose and dosing approach for future studies Evaluate early signs of treatment activity, such as tumor shrinkage, stable disease, or delayed tumor growth Explore biological changes in blood and tumor tissue that may help explain how N17350 works Study Hypothesis The study hypothesis is that N17350 can be administered safely by intratumoral injection at doses that are tolerable, and that treatment may lead to anti-tumor effects in some participants with advanced solid tumors, potentially by helping the immune system recognize and attack cancer cells.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
275
N17350 is a recombinant mutant porcine pancreatic elastase (PPE) developed to target the neutrophil elastase (ELANE) pathway.
Westmead Hospital
Westmead, New South Wales, Australia
Phase 1: Safety and tolerability of intratumoral N17350, including incidence of DLTs and adverse events
Safety and tolerability will be assessed by the incidence and severity of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), and by laboratory abnormalities graded per CTCAE
Time frame: DLTs: First 28 days; TEAEs/SAEs/laboratory abnormalities: From enrollment through 30 days after last dose assessed up to 4 months
Phase 2: Objective Response Rate (ORR) of lesions at RP2D/optimal dose(s)
ORR is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) in superficial and/or visceral lesions, assessed in separate tumor-specific expansion cohorts at the selected optimal dose(s)/RP2D(s), per protocol-defined response criteria
Time frame: From baseline disease assessment until disease progression or initiation of a new anticancer therapy, assessed up to 15 months
Objective Response Rate (ORR) in lesions (Phase 1)
ORR is defined as the proportion of participants with a best overall response of CR or PR in superficial and visceral lesions, assessed during dose escalation and backfill cohorts per RECIST v1.1 and/or IT-RECIST, as applicable
Time frame: From first dose through end of treatment (up to 12 weeks) and follow-up tumor assessments, assessed up to 12 months
Systemic exposure (PK) of N17350 following intratumoral administration
Systemic exposure to N17350 will be assessed by serum concentrations of active and inactive N17350
Time frame: From first dose through 30 days after last dose, assessed up to 4 months.
Systemic exposure (PK) of N17350 following intratumoral administration
Systemic exposure to N17350 will be assessed by serum concentrations of N17350, and derived PK parameter of Cmax
Time frame: From first dose through 30 days after last dose, assessed up to 4 months.
Systemic exposure (PK) of N17350 following intratumoral administration
Systemic exposure to N17350 will be assessed by serum concentrations of N17350, and derived PK parameter of Tmax
Time frame: From first dose through 30 days after last dose, assessed up to 4 months.
Systemic exposure (PK) of N17350 following intratumoral administration
Systemic exposure to N17350 will be assessed by serum concentrations of N17350, and derived PK parameter of area under the curve (AUC)
Time frame: From first dose through 30 days after last dose, assessed up to 4 months.
Systemic exposure (PK) of N17350 following intratumoral administration
Systemic exposure to N17350 will be assessed by serum concentrations of N17350, and derived PK parameter of N17350 half life
Time frame: From first dose through 30 days after last dose, assessed up to 4 months.
Immunogenicity of N17350 (anti-drug antibodies [ADA])
Immunogenicity will be assessed by the incidence and titers of anti-drug antibodies (ADA) to N17350
Time frame: From first dose through 30 days after last dose, assessed up to 4 months
Preliminary antitumor activity in lesions (ORR, DOR, DCR, CBR)
Antitumor activity in superficial and visceral lesions will be assessed by: Objective Response Rate (ORR): proportion of participants with best overall response of CR or PR Duration of Response (DOR): time from first documented response (CR or PR) to disease progression or death Disease Control Rate (DCR): proportion of participants with best overall response of CR, PR, or SD Clinical Benefit Rate (CBR): proportion of participants with CR, PR, or durable SD (as defined in the protocol) Responses will be assessed per RECIST v1.1 and/or IT-RECIST, as applicable.
Time frame: From first dose until disease progression or start of new anticancer therapy, assessed up to 15 months
Pharmacodynamic (PD) biomarkers
Changes from baseline in PD biomarkers measured in blood and/or tumor samples, as applicable, following intratumoral administration of N17350
Time frame: From first dose through 30 days after last dose, assessed up to 4 months
Progression-Free Survival (PFS) (Phase 2)
PFS is defined as the time from first dose to disease progression or death from any cause, assessed per RECIST v1.1 and/or IT-RECIST, as applicable
Time frame: From first dose until disease progression or death, assessed up to 15 months
Overall Survival (OS) (Phase 2)
OS is defined as the time from first dose to death from any cause.
Time frame: From first dose until death, assessed up to 15 months
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