Intratumoral N17350 in Advanced Solid Tumors

Prior treatment

• 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.
• Recent radiotherapy within 2 weeks prior to first dose.
• Unresolved toxicity from prior anticancer therapy to \>Grade 1 or not at baseline (except Grade ≤2 neuropathy and other allowed exceptions per protocol).
• Uncontrolled or unstable brain metastases (eligible only if neurologically stable for ≥4 weeks, and off steroids or on stable/decreasing steroids ≤10 mg/day prednisone equivalent; carcinomatous meningitis excluded).
• Active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose.
• Use of systemic anticoagulants (e.g., warfarin, LMWH, DOACs) within 14 days prior to first dose.
• Chronic systemic corticosteroids \>10 mg/day prednisone equivalent, or systemic immunosuppressive/anti-inflammatory medications within 4 weeks prior to first dose, except permitted topical/inhaled/local formulations or short courses for premedication per protocol.

Other illness

• 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.
• 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).
• Known allergy/hypersensitivity to N17350 or any excipients.

Lab values

• Chronic viral infections not meeting protocol criteria:
  • HBV with detectable DNA unless on appropriate antiviral therapy
  • Active HCV with detectable HCV RNA (treated HCV permitted if RNA undetectable)
  • HIV infection with CD4+ count \<300/μL, detectable viral load, or HIV-related illness within 6 months

Other

• Alpha-1 antitrypsin deficiency.
• Baseline QTcF \>480 ms.
• Pregnant or breastfeeding.

• 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 0-1.
• 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.
• Adequate recovery from prior therapy: toxicities from prior anticancer treatment resolved to Grade ≤1 or baseline (except alopecia, controlled endocrine toxicities, or other stable toxicities as allowed per protocol/sponsor).
• Adequate organ function, including hepatic, renal, and coagulation parameters per protocol-defined thresholds.
• Adequate bone marrow function without transfusion support within 7 days prior to enrollment, per protocol-defined thresholds.
• Tumor tissue requirements: willingness to provide a pre-treatment tumor biopsy and on-study post-treatment biopsy, if an accessible lesion is available and safe for biopsy, and biopsy does not interfere with injection/response assessment; and/or availability of archival tumor tissue (obtained within 2 years prior to treatment), per protocol.
• Contraception requirements: participants of reproductive potential agree to use effective contraception and avoid pregnancy/fathering children from screening through 30 days after last dose; women of childbearing potential must have a negative pregnancy test within 14 days prior to first dose, per protocol.