Solid Tumors
Conditions
Brief summary
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.
Interventions
DRUGHP007
Participate will recepit HP007 monotherpy with 4 dose groups
Sponsors
Parr Biotechnology (Hebei) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SAE | up to two years | Safety endpoints: incidence and severity of serious adverse events (SAE); Abnormal changes in laboratory and other tests with clinical significance |
| MTD | up to one year | Maximum tolerated dose (MTD) |
| RP2D | up to one year | Recommended dose for phase II trial |
| DLT | up to one year | Safety endpoints: incidence and severity of DLT |
| AE | up to two years | Safety endpoints: incidence and severity of adverse events (AE); Abnormal changes in laboratory and other tests with clinical significance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal half-life (t1/2) | up to two years | The pharmacokinetic parameters of WJ47156 ：terminal half-life (t1/2), |
| Peak concentration（Cmax） | up to two years | The pharmacokinetic parameters of WJ47156：peak concentration (Cmax) |
| the time to receive Cmax（Tmax） | up to two years | The pharmacokinetic parameters of HP007：the time to receive Cmax (Tmax) |
| Area Under the plasma concentration-time curve (AUC0-t, AUC0-∞) | up to two years | The pharmacokinetic parameters of HP007 ：area under the plasma concentration-time curve (AUC0-t, AUC0-∞) |
| ORR | up to two years | Efficacy endpoints: Objective response rate (ORR) per RECIST v1.1 or mRecist 1.1 or PCWG3 |
| DOR | up to two years | Efficacy endpoints: Duration of response (DOR) per RECIST v1.1 or mRecist 1.1 or PCWG3 |
| DCR | up to two years | Efficacy endpoints: Disease control rate (DCR) per RECIST v1.1 or mRecist 1.1 or PCWG3 |
| PFS | up to two years | Efficacy endpoints: Progression-free survival (PFS) per RECIST v1.1 or mRecist 1.1 or PCWG3 |
| OS | up to two years | Efficacy endpoints: Overall survival (OS) |
| Accumulation ratio for AUC | up to two years | The pharmacokinetic parameters of HP007：Accumulation ratio of area-under-the-curve, defined as steady-state AUC within one dosing interval divided by Day 1 AUC (typically AUC₀-₂₄h). It characterizes overall systemic exposure accumulation over the dosing cycle, used for efficacy and total exposure assessment. |
| the time to receive Cmax at steady state（Tmax,ss） | up to two years | The pharmacokinetic parameters of HP007 ：the time to receive Cmax at steady state（Tmax,ss）for the main PK parameters for multiple dose) |
| Area Under the plasma concentration-time curve at steady state (AUC0-t, ss) | up to two years | The pharmacokinetic parameters of HP007：area under the plasma concentration-time curve at steady state (AUC0-t, ss)for the main PK parameters for multiple dose) |
| ADA | up to two years | The incidence and changes of anti-drug antibody (ADA) after treatment were observed |
| Nab | up to two years | The incidence and changes of neutralizing antibody (Nab) after treatment were observed |
| Cytokines | up to one year | The changes of serum cytokines (IFN-α, IFN-γ, IL-6, IL-10, and chemokines IFN-γ-inducible protein 10 (IP-10) and TNF-α )in peripheral blood before and after treatment were observed |
| Steady-state peak concentration(Cmax,ss) | up to two years | The pharmacokinetic parameters of HP007 ：steady-state peak concentration(Cmax,ss) for the main PK parameters for multiple dose |
| Subtype of lymphocyte | up to one year | Flow cytometry was used to detect the changes in lymphocyte subsets in peripheral blood before and after treatment |
| Plasma trough concentration at steady state(Cmin,ss) | up to two years | The pharmacokinetic parameters of HP007：Plasma trough concentration at steady state(Cmin,ss) for the main PK parameters for multiple dose |
| Accumulation ratio for Cmax(RCmax) | up to two years | The pharmacokinetic parameters of HP007：Accumulation ratio of maximum plasma concentration, calculated as the ratio of steady-state Cmax to Day 1 Cmax after single dose. It reflects the extent of accumulation in peak drug concentration, relevant to peak-related acute toxicity. |
| Volume of distribution (Vd) | up to two years | The pharmacokinetic parameters of HP007 ：Volume of distribution (Vd) |
| Rate of clearance (C) | up to two years | The pharmacokinetic parameters of HP007 ：Rate of clearance (CL) |
Countries
China
Contacts
CONTACTNiannian Wang, Project Manager
Outcome results
None listed