A Phase 1/2 Open-Label, Dose Finding and Expansion Study to Investigate the Safety and Effectiveness and Determination of the Optimal Dose of N17350 Administered Intratumorally in Participants With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Onchilles Pharma Inc
- Enrollment
- 275
- Locations
- 1
- Primary Endpoint
- Phase 1: Safety and tolerability of intratumoral N17350, including incidence of DLTs and adverse events
Overview
Brief Summary
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:
- Does N17350 cause tumors to shrink or stop growing in some participants with advanced solid tumors?
- Are there any side effects for participants when taking N17350?
- What is the safest dose of N17350 and the dose that should be used for further study?
- 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:
- Receive injections of N17350 into tumor lesions every second week for 8 or 12 weeks
- Visit the clinic regularly for checkups, blood tests, and monitoring for side effects
- Have imaging scans (such as CT or MRI) to measure tumors and assess response
- Provide blood samples and, when required, tumor samples to help researchers understand how N17350 affects the tumor and the immune system
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 years (or legal age of consent in the study jurisdiction).
- •Able to provide written informed consent and willing/able to comply with study procedures, visits, and follow-up.
- •Advanced solid tumor malignancy (excluding lymphoma and other hematologic malignancies), with disease that has progressed on, is intolerant of, or is ineligible for standard therapies known to provide clinical benefit, or for whom no standard therapy is available.
- •ECOG performance status 0-
- •Measurable disease per IT-RECIST (Parts A1/A2) and RECIST v1.1 (Part A3), as applicable.
- •At least one injectable tumor lesion, meeting superficial or visceral criteria and deemed safe/accessible for injection:
- •Superficial lesions: ≥10 mm in longest diameter (or multiple lesions each ≥5 mm with aggregate longest diameter ≥10 mm), and ≤80 mm, accessible for direct injection (± ultrasound guidance).
- •Visceral lesions: ≥10 mm and ≤50 mm in longest diameter, accessible for direct injection.
- •Injected lesions must not involve/encase major blood vessels or otherwise pose an unacceptable bleeding/vascular risk, per investigator assessment and imaging review (as applicable).
- •Expansion (Part A3): at least 1 measurable lesion and at least 1 additional injectable lesion suitable for injection.
Exclusion Criteria
- •Serious psychiatric, medical, or other condition that would interfere with study participation or protocol procedures, in the investigator's judgment.
- •History of solid organ transplant.
- •Alpha-1 antitrypsin deficiency.
- •Hereditary or acquired bleeding disorder/coagulation factor deficiency.
- •Active autoimmune disease requiring systemic treatment within the past 6 months, except clinically stable autoimmune conditions in remission not requiring systemic therapy (per protocol).
- •Baseline QTcF \>480 ms.
- •Pregnant or breastfeeding.
- •Prior severe immune-mediated adverse event (imAE) from immunotherapy: ≥Grade 3 imAE within the past 16 weeks, any Grade 4 life-threatening imAE, or any neurologic/ocular AE of any grade (except controlled endocrine AEs on stable replacement therapy per protocol).
- •Another active malignancy (current or within the past 2 years) other than the disease under study, except specified low-risk cancers treated with curative intent or under active surveillance (per protocol).
- •Recent anticancer therapy: receipt of systemic anticancer therapy (including investigational agents) within 2 weeks prior to first dose (or 4 weeks for monoclonal antibodies/ADCs/other long half-life biologics), or within 5 half-lives, whichever is shorter.
Outcomes
Primary Outcomes
Phase 1: Safety and tolerability of intratumoral N17350, including incidence of DLTs and adverse events
Time Frame: DLTs: First 28 days; TEAEs/SAEs/laboratory abnormalities: From enrollment through 30 days after last dose assessed up to 4 months
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
Phase 2: Objective Response Rate (ORR) of lesions at RP2D/optimal dose(s)
Time Frame: From baseline disease assessment until disease progression or initiation of a new anticancer therapy, assessed up to 15 months
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
Secondary Outcomes
- Objective Response Rate (ORR) in lesions (Phase 1)(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(From first dose through 30 days after last dose, assessed up to 4 months.)
- Immunogenicity of N17350 (anti-drug antibodies [ADA])(From first dose through 30 days after last dose, assessed up to 4 months)
- Preliminary antitumor activity in lesions (ORR, DOR, DCR, CBR)(From first dose until disease progression or start of new anticancer therapy, assessed up to 15 months)
- Pharmacodynamic (PD) biomarkers(From first dose through 30 days after last dose, assessed up to 4 months)
- Progression-Free Survival (PFS) (Phase 2)(From first dose until disease progression or death, assessed up to 15 months)
- Overall Survival (OS) (Phase 2)(From first dose until death, assessed up to 15 months)