HP007 Monotherapy for Relapsed or Refractory Advanced Solid Tumors

Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of Intratumoral Injection of HP007 Injection as Monotherapy in Patients With Relapsed or Refractory Advanced Solid Tumors, and to Explore the Preliminary Efficacy of HP007

This study is an open-label, dose-escalation and expansion, Phase I clinical study to evaluate the safety, tolerability, PK characteristics and preliminary antitumor activity of HP007 monotherapy in patients with advanced malignant solid tumors.

Inclusion Criteria:

• Male/female, 18-75 years inclusive.
• Histologically-confirmed unresectable advanced tumors (breast cancer, HNSCC, cutaneous melanoma, prostate cancer, HCC, etc.);
• no effective standard therapy or disease relapse/metastasis post-standard-of-care.
• ECOG PS 0-1;
• expected survival ≥3 months.
• At least 1 measurable lesion by RECIST 1.1. Lesion in prior radiation field must have confirmed progression ≥4 weeks post-radiation. Prostate cancer subjects must meet PCWG3 progression criteria.
• At least one lesion suitable for repeated intratumoral injection.
• Adequate hematopoietic and organ function:
• Males and females of child-bearing potential agree effective contraception from ICF signature to 3 months after last dose.
• Voluntarily sign ICF and comply with study procedures.

Exclusion Criteria:

1. Past/current medical conditions

   • CNS or leptomeningeal metastasis.
   • Residual toxicity from prior anti-tumor therapy >Grade 1 (CTCAE 6.0), except alopecia and Grade 2 peripheral neuropathy without safety risk.
   • Poorly controlled pleural / ascitic / pericardial effusion requiring local intervention or repeated drainage.
   • Active autoimmune disease or high-risk history of recurrence; organ transplant with immunosuppression.
   • Interstitial lung disease / non-infectious pneumonitis; pulmonary embolism within prior 12 weeks.
   • Severe cardio-cerebrovascular events within 6 months; QTcF ≥470 msec; LVEF ≤50%; NYHA ≥III heart failure; history of long-QT syndrome or ongoing QTc-prolonging drugs.
   • Uncontrolled hypertension (SBP>160 mmHg and/or DBP>100 mmHg) or other uncontrolled systemic diseases.
   • High bleeding risk / coagulation disorders: inherited/acquired bleeding-thrombotic predisposition; major bleeding within 3 months; thrombolytics within 10 days; ongoing anticoagulant/antiplatelet therapy (except heparin for CVC patency).
   • Immunodeficiency; history of solid-organ or hematopoietic stem-cell transplantation.
   • Active TB within past 5 years.
   • Severe infection / trauma / GI perforation / fistula / tumor vascular invasion / bowel obstruction within 4 weeks; active infection or antibiotic use within prior 2 weeks (prophylaxis allowed); unexplained fever >38.5 ℃ (tumor-related fever may be allowed per Investigator judgment).
   • Other active malignancy within 3 years, except: cervical carcinoma in-situ, local basal-cell carcinoma, or malignancies cured ≥5 years without recurrence.

2. Prior medications & treatments

   • Local radiotherapy completed <1 week before first dose; >30% bone-marrow / extensive-field radiotherapy completed <4 weeks before first dose.
   • Anti-tumor therapy within 4 weeks or less than 5 half-lives (whichever shorter).
   • Systemic corticosteroids (>10 mg prednisone equivalent/day) or other immunosuppressants within 14 days.
   • Prior immunotherapy with irAEs ≥Grade 3.
   • Prior systemic TLR-agonist treatment (topical TLR agonists e.g. imiquimod permitted).
   • Vaccination within 1 month prior to enrolment.

3. Allergy, general status & others

   • Severe hypersensitivity (CTCAE 6.0 ≥Grade 3) to any investigational product component.
   • Active HBV / HCV, positive syphilis or HIV serology.
   • Participated in another interventional clinical trial within 4 weeks.
   • Major surgery within 4 weeks before screening or planned major surgery during study.
   • Alcohol / illicit-drug / substance abuse within 12 months.
   • Documented neurological/psychiatric disorders leading to poor compliance.
   • Pregnant or lactating females.
   • Subjects judged unsuitable by the Investigator for any other reason.