A Phase Ia/Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SG1906 in Patients With CLDN18.2-Positive Locally Advanced Unresectable or Metastatic Solid Tumors.
Overview
- Phase
- Phase 1
- Intervention
- SG1906
- Conditions
- Locally Advanced Unresectable or Metastatic Solid Tumors
- Sponsor
- Hangzhou Sumgen Biotech Co., Ltd.
- Enrollment
- 60
- Locations
- 9
- Primary Endpoint
- MTD/MAD/ RP2D
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
This is a Phase Ia/Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SG1906 in Patients with CLDN18.2-Positive Locally Advanced Unresectable or Metastatic Solid Tumors.
Detailed Description
After a screening period of up to 28 days for each study phase, qualified patients will be enrolled to receive their assigned dose of SG1906, administered every 2 weeks (Q2W), until disease progression or intolerable toxicity, starting of a new anticancer treatment, withdrawal of consent, lost to follow up, death, or end of the study, whichever occurs first. Phase Ia: Dose-escalation Stage The study population in Phase Ia includes patients with CLDN18.2-positive histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumor who have relapsed after standard therapy, have failed standard therapy, are intolerant to standard therapy, are not eligible for standard therapy, or refuse standard therapy. Phase Ib: Dose-expansion Stage The study population in this phase will include patients with histologically or cytologically confirmed CLDN18.2-positive locally advanced unresectable or metastatic G/GEJ cancer or PC who have failed to respond to standard therapy, have relapsed after standard therapy, or are intolerant to standard therapy; and who have disease progression as confirmed by the Investigator or documented by medical history.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must meet all the following criteria to be eligible for participation in this study:
- •Understand and voluntarily sign the informed consent form (ICF).
- •Age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
- •Expected survival time of ≥3 months.
- •Able to provide tumor tissue samples for CLDN18.2 detection.
- •Specific requirements for patients enrolled in Phase Ia and Phase Ib are as follows:
- •Phase Ia Dose Escalation Phase
- •Patients with CLDN18.2-positive histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumor who have relapsed after standard therapy, have failed standard therapy, are intolerant to standard therapy, are not eligible for standard therapy, or refuse standard therapy.
- •CLDN18.2 positivity is defined as H score ≥1 by central laboratory immunohistochemistry.
Exclusion Criteria
- •Patients who meet any of the following criteria cannot be enrolled:
- •Presence of active central nervous system metastatic lesions; presence of metastases to the brainstem or meninges, spinal cord metastases or compression. Exception: patients with previously treated brain metastases (e.g., surgery, radiation therapy) who are clinically stable for at least 4 weeks after treatment (calculated from the first dose of investigational drug) and have discontinued corticosteroids for ≥14 days prior to the administration of investigational drug; patients with untreated, asymptomatic brain metastases (i.e., no neurological symptoms, no need for corticosteroids, brain metastases ≤1.5 cm in length, no significant edema around the brain metastases).
- •Active autoimmune disease requiring systemic therapy within the past 2 years (e.g., use of immunomodulatory drugs, corticosteroids, or immunosuppressive medications); related replacement therapy is allowed (e.g., thyroid hormone, insulin, or physiologic corticosteroid replacement for renal or pituitary insufficiency).
- •Pyloric obstruction or any other condition that can cause long-term chronic nausea, persistent recurrent vomiting (≥3 vomit episodes in 24 hours) or diarrhea.
- •Patients who have recently developed gastrointestinal bleeding (i.e., a history of hematemesis, hematochezia, or melena within the past 3 months) without evidence of recovery confirmed by endoscopy or colonoscopy; or patients with evidence of risk of gastric bleeding.
- •Patients with active gastrointestinal disease including, but not limited to, gastric or duodenal ulcers, acute gastric or intestinal perforation, acute necrotizing pancreatitis, ulcerative enteritis, congenital megacolon or Crohn's disease.
- •Patients requiring long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs); patients who are using anticoagulants such as heparin at therapeutic doses or vitamin K antagonists (except for prophylaxis).
- •Presence of body fluid (hydrothorax, ascites, pericardial effusion, etc.) requiring local treatment or repeated drainage.
- •Unintentional weight loss ≥5% within 1 month prior to initial dose, even with peripheral or central intravenous nutritional support.
- •History of hemolytic anemia from any cause (including Evans syndrome).
Arms & Interventions
SG1906
SG1906 monotherapy intravenous (IV) infusion - Biweekly doses
Intervention: SG1906
Outcomes
Primary Outcomes
MTD/MAD/ RP2D
Time Frame: Through study completion, an average of one year
To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) for intravenous (IV) administration of SG1906 in patients with CLDN18.2-positive locally advanced unresectable or metastatic solid tumors.; To preliminarily determine the recommended Phase 2 dose (RP2D) of SG1906 given intravenously in patients with CLDN18.2-positive locally advanced unresectable or metastatic solid tumors.
Incidence of Treatment-Emergent Adverse Events
Time Frame: Through study completion, an average of one year
Number and percentage of AE which is calculated by worst CTCAE grade by CTCAE 5.0
Secondary Outcomes
- Pharmacokinetics (PK): Cmax(Through study completion, an average of one year)
- Efficacy endpoints:(Through study completion, an average of one year)
- Pharmacokinetics (PK): AUC(Through study completion, an average of one year)
- Immunogenicity endpoints:(Through study completion, an average of one year)
- Pharmacokinetics (PK):limination half-life (T1/2)(Through study completion, an average of one year)
- receptor occupancy (RO)(Through study completion, an average of one year)