GenSci143 for advanced solid tumors

A Phase 1, Multicenter, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of GenSci143 in Participants With Advanced Solid Tumors

This trial will test whether the experimental drug GenSci143 is safe and can shrink or slow tumors in adults with advanced solid cancers who have exhausted or cannot tolerate standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Changchun GeneScience Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 9 sites (Zhengzhou, Henan and 8 other locations)
• Trial ID: NCT07252414 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label dose-escalation and dose-expansion study of GenSci143 given by injection in adults with advanced solid tumors. The primary focus is on safety, tolerability, and pharmacokinetics, with secondary evaluation of preliminary anti-tumor activity. The dose-escalation phase will identify a recommended dose and the expansion cohorts include a cohort for metastatic castration-resistant prostate cancer (mCRPC) and a cohort for other advanced solid tumors. The trial is being conducted at three cancer centers in China and enrolls participants who have progressed on, are intolerant of, or lack standard treatment options.

Who should consider this trial

Good fit: Adults aged 18 or older with histologically or cytologically confirmed advanced solid tumors who have progressed after, are intolerant to, or lack standard therapy—with a specific expansion cohort for mCRPC patients previously treated with novel hormonal therapies.

Not a fit: Patients with early-stage disease who are eligible for effective standard treatments or those with uncontrolled medical conditions or poor organ function are unlikely to benefit from this investigational therapy.

Why it matters

Potential benefit: If safe and active, GenSci143 could offer a new treatment option for patients with advanced solid tumors who have few or no remaining standard therapies.

How similar studies have performed: Some early-phase trials of other experimental cancer drugs have produced tumor responses, but GenSci143 itself is investigational and has no established clinical results published yet.

Eligibility criteria

Inclusion Criteria:

* Voluntarily sign the ICF.
* Male or female participants ≥18 years old at the time of signing the ICF.
* Meet the requirements of tumor types as outlined below:

  1. Dose escalation: Participants with histologically or cytologically documented recurrent or metastatic advanced solid tumors, and who have progressed after standard therapy, are intolerant to standard therapy, or have no standard therapy available.
  2. Dose expansion:

Cohort 1: Participants with histologically or cytologically documented mCRPC，who had received at least one prior novel hormonal therapy (including but not limited to abiraterone, enzalutamide, darolutamide, apalutamide) and progressed on standard chemotherapy regimens, are intolerant to chemotherapy, or decline chemotherapy.

Cohort 2: Participants with histologically or cytologically documented other advanced solid tumors, and who have progressed after standard therapy, are intolerant to standard treatment, or have no standard therapy available.

* Life expectancy of ≥ 12 weeks.
* ECOG PS 0-1
* Have at least 1 evaluable tumor lesion according to RECIST v1.1. Participants with mCRPC who have bone only disease may be eligible on a case-by-case basis after discussion between the investigator and Sponsor
* Able to provide either archival or fresh biopsy formalin-fixed paraffin-embedded (FFPE) tumor samples.
* Adequate organ function at the time of screening, as outlined below:

  1. Hematology: Absolute neutrophil count (ANC) ≥ 1.5×109/L (1500/µL); platelet count (PLT)≥100×109/L (100,000/µL); hemoglobin (HGB) ≥ 90 g/L (9 g/dL) (have not received granulocyte colony-stimulating factor (G-CSF) within 7 days before the first dose of GenSci143, and have not received granulocyte-macrophage colony-stimulating factor (GM-CSF), blood transfusion, erythropoietin (EPO), platelet transfusion, thrombopoietin (TPO), or interleukin-11 (IL-11) within 14 days before the first dose of GenSci143).
  2. Liver function: Serum total bilirubin (TBIL) ≤ 1.5 upper limit of normal (ULN), and serum TBIL≤ 3×ULN in the presence of liver metastasis or documented Gilbert syndrome. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN if no liver metastasis; ALT and AST≤ 5×ULN in the presence of liver metastasis.
  3. Renal function: creatinine clearance (CLcr) ≥ 50 mL/min as calculated using the Cockcroft-Gault formula.
  4. Coagulation function: Prothrombin Time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) ≤ 1.5×ULN (or within target range if on anticoagulation therapy).
* Toxicities (other than alopecia) from previous anticancer therapy must have resolved to NCI-CTCAE v5.0 Grade ≤1.
* Women of childbearing potential (WOCBP) must have a serum pregnancy test negative within 7 days before the first dose of GenSci143. WOCBP must agree to use highly effective contraceptive methods and must not donate or retrieve ova for personal use from the time of informed consent until 6 months after the last dose of GenSci143. Male participants must agree to use highly effective contraceptive methods and must not freeze or donate sperm from the time of informed consent until 6 months after the last dose of GenSci143.

Exclusion Criteria:

* Participants with known spinal cord compression or active central nervous system (CNS) metastases, unless they are asymptomatic or have achieved post-treatment stability for \>4 weeks and discontinued corticosteroids for \>2 weeks before the first dose of GenSci143.
* History of other known malignancies within the past 3 years.
* Unstable thrombotic events requiring therapeutic intervention within 6 months before the first dose of GenSci143.
* Uncontrolled or clinically significant cardiovascular disease.
* Uncontrolled pleural fluid, pericardial effusion, or ascites requiring drainage, and/or diuretics within 2 weeks before the first dose of GenSci143.
* History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that requires steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. Any autoimmune, connective tissue, or inflammatory disorders with suspected pulmonary involvement.
* Pregnant, breastfeeding, or planning to become pregnant.
* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
* Known human immunodeficiency virus (HIV) infection
* Uncontrolled infection that requires systemic therapy with IV antibiotics, antivirals, or antifungals within 1 week before the first dose of GenSci143.
* Major surgery (excluding diagnostic surgery), radiotherapy, and immunotherapy within 4 weeks before the first dose of medication; Chemotherapy or antibody therapy within 3 weeks; Endocrine therapy and small molecule-targeted therapy within 2 weeks or 5 half-lives(whichever is shorter). Androgen-deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues (either GnRH agonists or GnRH antagonists) was allowed for men with prostate cancer.
* Received any live vaccine within 4 weeks before the first dose of GenSci143 or intend to receive a live vaccine during the study.
* History of allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
* Prior treatment with a topoisomerase inhibitor or an ADC that consists of a topoisomerase inhibitor.
* History of severe hypersensitivity reactions to GenSci143 and/or excipients in the drug product, or other monoclonal antibodies.
* Any illness (uncontrolled hypertension, serious diabetes mellitus, thyroid disorders, and psychiatric disorders, etc.) or other conditions that are not eligible for inclusion based on the investigator's judgment.

Where this trial is running

Zhengzhou, Henan and 8 other locations

• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• Hubei Cancer Hospital — Wuhan, Hubei, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (Recruiting)
• Shandong Cancer Hospital — Jinan, Shandong, China (Not_yet_recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)
• Zhongshan Hospital Affiliated to Fudan University — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• The First Hospital of Shanxi Medical University — Taiyuan, Shanxi, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Dingwei Ye

Conditions Advanced Solid Tumors