A Study of GNC-035, a Tetra-specific Antibody, in Participants With Locally Advanced or Metastatic Solid Tumors

An Open-Label, Multi-Center, Phase I Study to Evaluate the Safety, Tolerability，Pharmacokinetic/Pharmacodynamics and Anti-tumor Activity of Tetra-specific Antibody GNC-035 in Participants With Locally Advanced or Metastatic Solid Tumors

In this study, the safety, tolerability and preliminary effectiveness of GNC-035 in participants with locally advanced or metastatic solid tumors will be investigated to assess the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MAD) for MTD is not reached of GNC-035.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer; Solid Tumor
• Intervention / Treatment: Drug: GNC-035

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Sichuan, Sichuan, China, 610041
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The participants could understand and sign the informed consent form, and must participate voluntarily
2. No gender limit
3. Age: ≥18 years old
4. Histologically or cytologically documented, locally advanced or metastatic solid tumour,and disease progression confirmed by imaging or other objective evidence after having received standard treatment; or patients with refractory solid tumors who cannot tolerate standard treatment or have contraindications to standard treatment
5. Measurable disease at baseline as assessed by the Investigator per RECIST v1.1
6. ECOG Performance Status ≤ 1
7. Life expectancy estimated to be at least 3 months
8. Acceptable bone marrow function： Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, and hemoglobin ≥ 90 g/L.

9. Acceptable renal function:

   Creatinine (Cr) ≤ 1.5ULN or creatinine clearance (Ccr) ≥ 50 mL/min (calculated by the study site), urine protein ≤ 2 + or ≤ 1000 mg/24h (urine).

10. Acceptable liver function:

    AST and ALT ≤ 3.0xULN (≤ 5.0ULN for patients with tumor infiltrative changes in the liver) total bilirubin ≤ 1.5xULN (≤ 3ULN for Gilbert's syndrome)

11. Coagulation function: fibrinogen ≥ 1.5 g/L, activated partial thromboplastin time (APTT) and prothrombin time (PT) ≤1.5×ULN
12. Female participants with fertility or male participants whose partner(s) are fertile must take effective contraceptive measures from 7 days prior to the first administration to 12 weeks after the administration. Female participants with fertility must have a negative serum/urine pregnancy test in 7 days prior to the first dose.

Exclusion Criteria:

1. Active infection requiring intravenous antibiotics and not treated within 1 week prior to enrollment, except for prophylactic antibiotics for needle stick or biopsy
2. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive or HBcAb positive with HBV-DNA detection ≥ 10e4), or hepatitis C virus infection (HCV antibody positive with HCV-RNA ≥ ULN)
3. Toxicity from prior anticancer therapy has not been reduced to Grade I as defined in CTCAE v5.0 (with the exception of symptoms related to myelosuppression, such as neutropenia, anemia, thrombocytopenia) or to the levels specified in the inclusion criteria. Alopecia and irreversible toxicity from prior anticancer therapy (defined as stable for ≥ 2 months) allowed in the opinion of the investigator/sponsor; irAE in patients who have received prior immunotherapy and who are no longer able to receive immunotherapy as recommended by guidelines
4. Patients at risk for active autoimmune diseases, or with a history of autoimmune diseases, may have central nervous system involvement, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's syndrome, polyangitic granulomatosis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain - Barré syndrome), etc.
5. Pulmonary disease defined as ≥ Grade 3 according to NCI-CTCAEv5.0, including patients with resting dyspnea, or requiring continuous oxygen therapy, or with a history of interstitial lung disease (ILD)
6. Patients with prior organ transplant
7. Left ventricular ejection fraction ≤ 50%, or history of significant cardiac disease within 1 year
8. History or presence of thrombotic events such as deep venous thrombosis, arterial thrombosis, and pulmonary embolism
9. Received chemotherapy, molecular targeted therapy, etc., at 14 or 5 half-lives (whichever is shorter) of the first dose. Patients who have received radiotherapy, antibody therapy (such as PD-L1) or study drug within 28 days
10. Patients who had undergone major surgery within 28 days prior to dosing in this study, or who were scheduled to undergo major surgery during this study ("major surgery"was defined by the investigator)
11. Hypertension poorly controlled on medication (systolic > 150 mmHg or diastolic > 100 mmHg)
12. Previous or concomitant central nervous system disease
13. Has receivedany other clinical trial within 4 weeks prior to GNC-035 treatment

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-035; Patients receive GNC-035 as a 24-hour continuous intravenous infusion (cIV, QD) for 2 weeks (a 2-week cycle). Participants with no intolerable AEs could continue for another three cycles.	Drug: GNC-035; Administration by intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TEAE	Treatment-Emergent Adverse Event	Up to 2 years
DLT	Dose limiting toxicity	Up to 2 weeks
MTD or MAD	Maximum tolerated dose or maximum administrated dose	Up to 2 weeks
The recommended dose for future clinical study	The recommended dose for future clinical study	Up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free Survival	Up to 2 years
DCR	Disease Control Rate	Up to 2 years
DOR	Duration of Response	Up to 2 years
AESI	Adverse Events of special interest	Up to 2 years
Cmax	Maximum serum concentration of GNC-035	Up to 2 weeks
Tmax	Time to maximum serum concentration (Tmax) of GNC-035	Up to 2 weeks
T1/2	Half-life of GNC-035	Up to 2 weeks
Incidence and titer of ADA	Anti-drug antibody	Up to 2 years
ORR	Objective Response Rate	Up to 2 years

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: SystImmune Inc.
• Investigators: Principal Investigator: Yongsheng Wang, West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Estimated): June 1, 2023
• Study Completion (Estimated): June 1, 2023

Study Registration Dates

• First Submitted: August 22, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 10, 2021

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Lung Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms
• Other Study ID Numbers: GNC-035-101（V1.1）

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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