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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumor; Gastrointestinal Tumors
• Intervention / Treatment: Drug: GNC-077

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: 15013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hospital
      • Contact: Lin Shen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 > 150 mmHg or diastolic blood pressure > 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GNC-077; Participants receive GNC-077 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: GNC-077; Administration by intravenous infusion for a cycle of 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia: Dose limiting toxicity (DLT)	DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.	Up to 21 days after the first dose
Phase Ia: Maximum tolerated dose (MTD)	MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.	Up to 21 days after the first dose
Phase Ia: Treatment-Emergent Adverse Event (TEAE)	TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of GNC-077 . The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-077.	Up to approximately 24 months
Phase Ib: Recommended Phase II Dose (RP2D)	The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of GNC-077.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.	Up to approximately 24 months
AUC0-t	AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.	Up to approximately 24 months
Cmax	Maximum serum concentration (Cmax) of GNC-077 will be investigated.	Up to approximately 24 months
Tmax	Time to maximum serum concentration (Tmax) of GNC-077 will be investigated.	Up to approximately 24 months
AUC0-inf	AUC0-inf is defined as area under the concentration-time curve from 0 to inf.	Up to approximately 24 months
CL (Clearance)	CL in the serum of GNC-077 per unit of time will be investigated.	Up to approximately 24 months
T1/2	Half-life (T1/2) of GNC-077 will be investigated.	Up to approximately 24 months
ADA (anti-drug antibody)	Frequency of anti-GNC-077 antibody (ADA) will be investigated.	Up to approximately 24 months
Progression-free survival (PFS)	The PFS is defined as the time from the participant's first dose of GNC-077 to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 25, 2024
• First Submitted That Met QC Criteria: December 25, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: GNC-077-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No