Clinical trial NCT06755242: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Gastrointestinal Tumors
Solid Tumor
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2025-01-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Able to understand the informed consent form, voluntarily participate in and sign the informed consent form;
2. Gender is not limited;
3. Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib);
4. Patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors confirmed by histopathology and/or cytology who failed standard treatment;
5. Must have at least one measurable lesion that meets the RECIST v1.1 definition;
6. Have archived primary or recurrent tumor tissue specimens that can be submitted for central review;
7. ECOG ≤1;
8. The expected survival time as judged by the investigators was ≥3 months;
9. Bone marrow function, renal function and liver function need to meet the requirements;
10. Coagulation function: fibrinogen ≥1.5 g/L; Activated partial thromboplastin time (APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN;
11. 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;
12. Subjects were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion Criteria:

1. 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;
2. 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;
3. Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection or hepatitis C virus infection;
4. Toxicity from prior antineoplastic therapy is not reduced to grade I as defined in CTCAE, version 5.0;
5. Patients at risk for active autoimmune disease or with a history of autoimmune disease may have central nervous system involvement;
6. 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;
7. Patients with previous allogeneic hematopoietic stem cell transplantation or organ transplantation;
8. Had a history of severe cardiovascular and cerebrovascular diseases;
9. Patients with or with unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism within 6 months before screening;
10. Brain parenchymal metastases and/or meningeal metastases or spinal cord compression, excluding stable and asymptomatic brain parenchymal metastases;
11. Patients with massive or symptomatic effusions or poorly controlled effusions;
12. Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large arteries;
13. Subjects with clinically significant bleeding or significant bleeding tendency within the previous 4 weeks were screened;
14. Complicated with other malignant tumors within 3 years before the first administration;
15. Poorly controlled hypertension (systolic blood pressure \&gt; 150 mmHg or diastolic blood pressure \&gt; 100 mmHg);
16. Diabetic patients with poor glycemic control;
17. Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of GNC-077;
18. Who had participated in a clinical trial of an unmarketed drug within 4 weeks before the trial dose;
19. Had received a live vaccine within 4 weeks before the trial dose;
20. Other circumstances that the investigator deemed inappropriate for participation in the trial.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 21 days after the first dose
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 21 days after the first dose
measure: Phase Ia: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Cmax
timeFrame: Up to approximately 24 months
measure: Tmax
timeFrame: Up to approximately 24 months
measure: AUC0-inf
timeFrame: Up to approximately 24 months
measure: AUC0-t
timeFrame: Up to approximately 24 months
measure: CL (Clearance)
timeFrame: Up to approximately 24 months
measure: T1/2
timeFrame: Up to approximately 24 months
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: