A Study of GNC-077 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

Official title

An Open-label, Multicenter, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics or Preliminary Efficacy and Antitumor Activity of GNC-077 Multi-specific Antibody Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

Overview

This study is an open-label, multicenter, dose-escalation and cohort expansion phase I clinical study to evaluate the safety, tolerability, pharmacokinetics characteristics or preliminary efficacy and antitumor activity in patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors.

Interventions

• Drug GNC-077
  Administration by intravenous infusion for a cycle of 3 weeks.

Primary outcome measures

• Phase Ia: Dose limiting toxicity (DLT) [Time frame: Up to 21 days after the first dose]
• Phase Ia: Maximum tolerated dose (MTD) [Time frame: Up to 21 days after the first dose]
• Phase Ia: Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Phase Ib: Recommended Phase II Dose (RP2D) [Time frame: Up to approximately 24 months]

Secondary outcome measures (9)

• Cmax [Time frame: Up to approximately 24 months]
• Tmax [Time frame: Up to approximately 24 months]
• AUC0-inf [Time frame: Up to approximately 24 months]
• AUC0-t [Time frame: Up to approximately 24 months]
• CL (Clearance) [Time frame: Up to approximately 24 months]
• T1/2 [Time frame: Up to approximately 24 months]
• ADA (anti-drug antibody) [Time frame: Up to approximately 24 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Progression-free survival (PFS) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• Able to understand the informed consent form, voluntarily participate in and sign the informed consent form;
• Gender is not limited;
• Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib);
• Patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors confirmed by histopathology and/or cytology who failed standard treatment;
• Must have at least one measurable lesion that meets the RECIST v1.1 definition;
• Have archived primary or recurrent tumor tissue specimens that can be submitted for central review;
• ECOG ≤1;
• The expected survival time as judged by the investigators was ≥3 months;
• Bone marrow function, renal function and liver function need to meet the requirements;
• Coagulation function: fibrinogen ≥1.5 g/L; Activated partial thromboplastin time (APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN;
• Fertile female subjects or male subjects with fertile partners must use highly effective contraception from 7 days before the first dose until 12 weeks after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose;
• Subjects were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion criteria

• Chemotherapy, biological therapy, immunotherapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
• Patients with active infection requiring intravenous antibiotics that had not been completed more than 1 week before enrollment, with the exception of prophylactic antibiotics for puncture or biopsy;
• Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection or hepatitis C virus infection;
• Toxicity from prior antineoplastic therapy is not reduced to grade I as defined in CTCAE, version 5.0;
• Patients at risk for active autoimmune disease or with a history of autoimmune disease may have central nervous system involvement;
• Pulmonary disease defined as ≥ grade 3 according to NCI-CTCAE v5.0; A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis;
• Patients with previous allogeneic hematopoietic stem cell transplantation or organ transplantation;
• Had a history of severe cardiovascular and cerebrovascular diseases;
• Patients with or with unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism within 6 months before screening;
• Brain parenchymal metastases and/or meningeal metastases or spinal cord compression, excluding stable and asymptomatic brain parenchymal metastases;
• Patients with massive or symptomatic effusions or poorly controlled effusions;
• Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large arteries;
• Subjects with clinically significant bleeding or significant bleeding tendency within the previous 4 weeks were screened;
• Complicated with other malignant tumors within 3 years before the first administration;
• Poorly controlled hypertension (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
• Diabetic patients with poor glycemic control;
• Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of GNC-077;
• Who had participated in a clinical trial of an unmarketed drug within 4 weeks before the trial dose;
• Had received a live vaccine within 4 weeks before the trial dose;
• Other circumstances that the investigator deemed inappropriate for participation in the trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT06755242 · GNC-077-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗