A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Potential Anti-tumor Effects of SSGJ-705 in Patients With Advanced or Metastatic HER2-expressing Solid Tumors

Study Overview
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Brief Summary
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The study will consist of two parts: a dose-escalation part (Part 1) and a dose expansion part (Part 2). In both study parts, SSGJ-705 will be administered，the administration duration may be adjusted based on outcomes of previous patients if necessary) followed by safety, PK, PD, potential anti tumor effects and immunogenicity evaluation.

Official Title
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A Phase I, Multicenter, Open-Label, First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Potential Anti-tumor Effects of SSGJ-705 in Patients With Advanced or Metastatic HER2-expressing Solid Tumors

Conditions
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Receptor, ErbB-2

Intervention / Treatment
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* Drug: SSGJ-705


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 year, male or female. Life expectancy ≥12 weeks (according to Investigator's judgement). Patients with histologically or cytologically confirmed locally advanced or metastatic non resectable HER2-expressing Solid Tumors Patients who have at least one measurable lesion (radiation-naïve) according to RECIST v1.1 ECOG performance status 0-1 Adequate organ and bone marrow function evaluated by laboratory tests Male patients who are surgically sterilized or who agree to use highly effective contraceptive measures during the study and for at least 6 months after administration of the last study drug dose Willing to provide written informed consent and willing and able to comply with all study procedures. Exclusion Criteria: Receive chemotherapy, targeted therapy, or other antitumor therapy within 3 weeks prior to initial dosing Patients whose toxicity due to previous anticancer therapy has not been reduced to NCI CTCAE Grade 1 or lower, or any greater than NCI CTCAE 1 AE exists within 2 weeks before enrollment, not including hair loss and fatigue Patients requiring systemic systemic therapy with systemic hormones or other immunosuppressive agents within 4 weeks prior to initial administration and during the study period Previous cumulative doses of adriamycin > 720 mg/m2, adriamycin >360 mg/m2 or other cumulative doses of adriamycin were converted to equal doses of adriamycin >360 mg/m2 Patients who underwent major surgery within 4 weeks of initial dosing and have not fully recovered or who plan to undergo major surgery during the trial In addition to palliative radiotherapy, other anticancer treatments not specified in the protocol are planned for the duration of the trial Always received total pelvic radiotherapy Had an active or prior autoimmune or inflammatory disease within the last 3 years prior to study treatment Severe disease of cardiovascular and cerebrovascular diseases History of active tuberculosis A history of (non-infectious) pneumonia/interstitial pneumonia or a history of present pneumonia/interstitial pneumonia requiring steroid treatment Severe dyspnea or the need for supplemental oxygen therapy at rest due to complications of advanced malignancy; Newly diagnosed or symptomatic central nervous system (CNS) metastasis, spinal cord compression, or cancerous meningitis Persons with a history of primary immunodeficiency disease, including but not limited to HIV-positive serum Hepatitis B virus (HBV) and hepatitis C virus (HCV) positive subjects Women/men who are pregnant or breast-feeding or planning to give birth A history of mental or substance abuse that may affect study compliance Allergy to other antibody drugs or to any excipients in the study drug Who received live vaccine within 30 days prior to initial administration (within 72 hours for COVID-19 vaccine), or who plan to receive any live vaccine during the study Previous organ and allogeneic stem cell transplants (except transplants that do not require immunosuppressive therapy, such as corneal and hair transplants) Participated in any medical device or drug clinical study within 1 month prior to screening The inestigators considered that this would significantly increase the risk of administration of the investigational drug, or that it would affect efficacy evaluation or other conditions requiring exclusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HER2-expressing Solid Tumors<br>SSGJ-705 Administered via intravenous (IV) infusion | Drug: SSGJ-705<br>* 0.1, 1, 3, 6, 10, 15 or 20mg/kg, IV, Day 1, 8, 15 of each treatment cycle, up to disease progression or intolerable toxicity, death, early withdrawal from the study or loss to follow-up, withdrawal of consent, or the end of the treatment period, whichever occurs first. Every 4 weeks a treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | Dose-limiting toxicity（part 1） | At the end of Cycle 1 (each cycle is 28 days) | 
| MTD | maximum tolerated dose（part 1） | up to 1 years | 
| RP2D | Objective response rate (ORR) per RECIST 1.1 criteria according to investigators recommended Phase II dose（part 1） | up to 1 years | 
| ORR | Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment（part 2） | up to 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | the safety of SSGJ-705 in patients with advanced or metastatic HER2-expressing solid tumors who have failed standard treatment | up to 1 years | 
| Maximum Plasma Concentration (Cmax) | To evaluate the Cmax of single and multiple doses of SSGJ-705 in patients with advanced or metastatic HER2 expressing solid tumors who have failed standard treatments | up to 1 years | 
| Area Under the Curve (AUC) | To evaluate the AUC of single and multiple doses of SSGJ-705 in patients with advanced or metastatic HER2 expressing solid tumors who have failed standard treatments | up to 1 years | 
| incidence of anti-609A antibodies | incidence of anti-609A antibodies | up to 1 years | 
| Median Progression-free Survival (PFS) | The Kaplan-Meier method will be used to estimate median PFS. | up to 1 years | 
| Overall Survival (OS) | The Kaplan-Meier method will be used to estimate median OS. | up to 1 years |