Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GKL-006 Injection in Combination With TACE in Unresectable Hepatocellular Carcinoma

NCT07845266 | Completed Phase 1

• 1 other identifier: GKL006HCC01
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase Ia study evaluated the safety and tolerability of a single escalating dose via intravenous infusion of the autologous invariant natural killer T cells (iNKT-cell) product GKL-006 in combination with transarterial chemoembolisation (TACE) in participants with unresectable hepatocellular carcinoma (uHCC). The study aimed to characterise dose-limiting toxicities (DLT), determine the maximum tolerated dose (MTD), and assess pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumour activity.

Conditions

Hepatocellular Carcinoma (HCC); Unresectable Hepatocellular Carcinoma

Keywords

invariant natural killer T cells; iNKT cells; GKL-006; Unresectable Hepatocellular Carcinoma; TACE

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose（MTD）of GKL-006

  The MTD determined from protocol-defined DLTs under the 3+3 dose-escalation design.

  From the GKL-006 infusion until 28 days.

• Incidence of Dose-Limiting Toxicities (DLTs)

  Observe the dose limiting toxicity, and Incidence of dose-limiting toxicities(DLT) will be assessed

  From GKL-006 infusion through Day 28

Secondary Outcomes (14)

• Incidence and Severity of Adverse Events

  From GKL-006 infusion though 28 days.

• Cmax

  From 1 hour pre-dose of GKL-006 injection through 12 weeks

• Tmax

  From 1 hour pre-dose of GKL-006 injection through 12 weeks

• AUC

  From 1 hour pre-dose of GKL-006 injection through 12 weeks

• t1/2z

  From 1 hour pre-dose of GKL-006 injection through 12 weeks

Study Arms (4)

TACE

ACTIVE COMPARATOR

Participants will receive transarterial chemoembolization (TACE) alone according to the study protocol.

Drug: transarterial chemoembolization

Low-Dose Cohort

EXPERIMENTAL

Participants will receive TACE and (1.0±0.3)×10\^8 iNKT cells/m\^2 of GKL-006 Injection sequentially according to the study protocol.

Biological: GKL-006 Injection; Drug: transarterial chemoembolization

Medium-Dose Cohort

EXPERIMENTAL

Participants will receive TACE and (3.0±0.9)×10\^8 iNKT cells/m\^2 of GKL-006 Injection sequentially according to the study protocol.

Biological: GKL-006 Injection; Drug: transarterial chemoembolization

High-Dose Cohort

EXPERIMENTAL

Participants will receive TACE and (9.0±2.7)×10\^8 iNKT cells/m\^2 of GKL-006 Injection sequentially according to the study protocol.

Biological: GKL-006 Injection; Drug: transarterial chemoembolization

Interventions

GKL-006 Injection BIOLOGICAL

Autologous iNKT cells collected and reinfused after in vitro cultivation.

High-Dose Cohort; Low-Dose Cohort; Medium-Dose Cohort

transarterial chemoembolization DRUG

A standard locoregional therapy for hepatocellular carcinoma.

High-Dose Cohort; Low-Dose Cohort; Medium-Dose Cohort; TACE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participates and provides written informed consent.
• Aged ≥18 years, male or female.
• Unresectable primary hepatocellular carcinoma (HCC) confirmed by histology, cytology, or imaging (dynamic CT or MRI). Unresectable disease includes technically unresectable disease or disease for which surgery is not feasible or is declined for other reasons.
• CNLC stage II-IIIa.
• Suitable for TACE and total tumour volume ≤50% of the liver volume.
• At least one measurable HCC lesion per mRECIST.
• Tumour confined to the liver, with no extrahepatic spread or major vascular invasion (Vp3 or Vp4 portal vein tumour thrombus).
• Child-Pugh score ≤9 within 7 days before enrolment.
• ECOG performance status of 0-2
• Life expectancy ≥24 weeks.
• Adequate haematologic and organ function:
• WBC ≥2 × 10\^9/L;
• haemoglobin ≥90 g/L;
• ANC ≥1.5 × 10\^9/L;
• platelets ≥50 × 10\^9/L;

You may not qualify if:

• Hypersensitivity to immunotherapy or related medications.
• Another malignancy within the previous 5 years or a concurrent uncontrolled malignancy, except cured basal cell carcinoma, carcinoma in situ, or breast cancer with no recurrence for \>3 years after curative surgery.
• History of organ transplantation.
• Any contraindication to TACE, as determined by the investigator.
• Histologically or cytologically confirmed combined HCC-cholangiocarcinoma, fibrolamellar HCC, sarcomatoid HCC, or another mixed carcinoma.
• Active, known, or suspected autoimmune disease.
• Systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 4 weeks before screening.
• Infiltrative tumour growth or extrahepatic metastasis on imaging.
• Hepatic encephalopathy.
• Symptomatic ascites or pleural effusion.
• History or current evidence of idiopathic pulmonary fibrosis, interstitial pneumonitis, pneumoconiosis, drug-induced pneumonitis, or active pneumonitis on screening CT.
• Poorly controlled cardiovascular disease.
• Uncontrolled hypertension despite medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
• Urine protein ≥2+ within 7 days before enrolment with confirmed 24-hour urine protein \>1.0 g.
• Any of the following bleeding risks:

Sponsors & Collaborators

• Beijing Gene Key Life Technology Co., Ltd: lead

Study Sites (2)

Beijing Ditan Hospital Chaoyang Campus

Beijing, Beijing Municipality, 100015, China

Location

Beijing Youan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100069, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Jun Lv, MD

  Beijing YouAn Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This Phase 1a study uses a modified 3+3 dose-escalation design with three experimental dose cohorts and one active comparator arm. Within each dose cohort, participants were randomized to receive TACE plus GKL-006 at the designated dose level or TACE alone.

Study Record Dates

• First Submitted: September 22, 2026
• First Posted: September 28, 2026
• Study Start: April 16, 2024
• Primary Completion: April 9, 2025
• Study Completion: December 4, 2025
• Last Updated: September 28, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)