Advanced Pancreatic Cancer, Ductal Adenocarcinoma of Pancreas
Conditions
Keywords
GKL-006, iNKT cells
Brief summary
This is a Phase I/IIa, multicenter study designed to evaluate the safety, tolerability, and efficacy of GKL-006 injection in patients with ductal adenocarcinoma of pancreas.
Detailed description
This study will evaluate GKL-006 injection in combination with nab-paclitaxel and gemcitabine in patients with advanced pancreatic cancer. Phase I will primarily assess tolerability and safety, and will also evaluate preliminary efficacy and pharmacokinetic and pharmacodynamic characteristics. Phase II will primarily evaluate efficacy, with further assessment of safety and pharmacokinetic and pharmacodynamic characteristics.
Interventions
BIOLOGICALGKL-006 injection
GKL-006 injection will be administered at the protocol-defined dose every 2 weeks. Participants in Phase I will receive the assigned low or high dose, and recommended dose in Phase II.
Nab-paclitaxel and Gemcitabine are given intravenously as a combination chemotherapy regimen according to the study protocol.
Sponsors
Beijing Gene Key Life Technology Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Participants and investigators are not masked to treatment assignment. Tumour response assessments are performed by a blinded Independent Review Committee.
Intervention model description
The study consists of two sequential parts. In Phase I, participants will be enrolled sequentially into a low-dose cohort followed by a high-dose cohort. In Phase II, participants will be assigned in parallel to the investigational arm or the control arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18-75 years, inclusive, with no sex restriction. 2. Histologically or cytologically confirmed unresectable locally advanced or metastatic PDAC. 3. No prior systemic therapy for unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma. Prior neoadjuvant or adjuvant therapy will not be considered prior systemic therapy for advanced disease. 4. For patients with postoperative recurrence or metastasis who previously received neoadjuvant or adjuvant therapy, disease progression or recurrence must have occurred at least 6 months after completion of prior therapy. 5. At least one measurable lesion during screening, as defined by RECIST version 1.1. 6. Able to understand and voluntarily sign the ICF, communicate adequately with the investigator, comply with study procedures and follow-up, and meet all study requirements. 7. ECOG PS 0 or 1 and a life expectancy of at least 12 weeks. 8. Adequate haematological and organ function, as demonstrated by protocol-specified laboratory values obtained within 14 days before enrolment or randomisation. 9. No traditional Chinese medicine with an antitumour indication within 7 days before enrolment or randomisation. 10. Participants of reproductive potential must use medically accepted contraception during study treatment and for 6 months after the end of treatment.
Exclusion criteria
1. Known hypersensitivity to any component of the study treatments. 2. Other unresolved malignancy within 5 years or concurrently, except specified adequately treated malignancies. 3. Active, known, or suspected autoimmune disease, or systemic corticosteroid/immunosuppressive therapy within 4 weeks before screening. 4. Major surgery or severe trauma within 6 months before screening, or planned major surgery during the study. 5. Known brain or meningeal metastases, except stable brain metastases. 6. Symptomatic ascites or pleural effusion. 7. History or presence of clinically significant interstitial lung disease or active infection. 8. Poorly controlled or clinically significant cardiovascular disease, including inadequately controlled hypertension within 7 days, unstable angina within 6 months, or acute myocardial infarction within 1 year before enrolment. 9. Clinically significant proteinuria within 7 days before enrolment. 10. Toxicity from prior anticancer therapy not recovered to protocol-specified levels. 11. Clinically significant bleeding within 4 weeks, GI bleeding within 6 months, major-vessel invasion with a high bleeding risk, a known bleeding/thrombotic disorder, or arterial/venous thromboembolism within 6 months before enrolment/randomisation. 12. History or presence of tumour-related GI obstruction requiring treatment. 13. Active systemic infection requiring treatment within 2 weeks, or unexplained fever or clinically significant leukocytosis within 7 days before enrolment. 14. Congenital or acquired immunodeficiency, active syphilis or another serious active infection, or HBV/HCV infection with detectable viral load at screening. 15. Any contraindication to IL-2. 16. Prior genetically modified cell therapy, or non-genetically modified cell therapy within 6 months before screening. 17. Pregnancy or breastfeeding. 18. Receipt of an attenuated vaccine or participation in another drug/device clinical study within 4 weeks before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities | From the first dose until 42 days | The number and percentage of participants experiencing a dose-limiting toxicity during the protocol-defined DLT evaluation period. Dose-limiting toxicities will be assessed according to the criteria specified in the protocol. |
| Incidence and Severity of Adverse Events and Serious Adverse Events | Up to 18 months | The number and percentage of participants experiencing adverse events and serious adverse events, including their severity. The number and percentage of participants with clinically significant abnormalities in laboratory tests, 12-lead electrocardiograms, physical examinations, and vital signs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | Up to 18 months | The time from randomisation/enrolment/first treatment to the first documented disease progression or death from any cause, whichever occurs first. Tumour response will be assessed according to RECIST version 1.1. |
| Objective Response Rate | Up to 18 months | The percentage of participants with a best overall response of complete response or partial response according to RECIST version 1.1. |
| Disease Control Rate | Up to 18 months | The percentage of participants with a best overall response of complete response, partial response, or stable disease according to RECIST version 1.1. |
| Duration of Response | Up to 18 months | The time from the first documented response to the first documented disease progression or death from any cause, whichever occurs first. Assessments will be performed according to RECIST version 1.1. |
| Time to Progression | Up to 18 months | The time from randomisation/enrolment/ the first treatment to the first documented disease progression according to RECIST version 1.1. |
| One-Year Overall Survival Rate | From enrolment until 1 year | The probability of participants remaining alive at 1 year after enrolment. |
| Overall Survival | Up to 18 months | The time from randomisation/enrolment/ the first dose to death from any cause. |
| Tumour Markers | Up to 18 months | Change from baseline in serum carbohydrate antigen 19-9 (CA199), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA 125) levels. |
| Quality of Life Change From Baseline | Up to 18 months | Health-related quality of life measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. |
| Maximum Observed Peripheral Blood iNKT-Cell Concentration (Cmax) | Up to 6 months | Pharmacokinetic Parameters |
| Time to Maximum Peripheral Blood iNKT-Cell Concentration (Tmax) | Up to 6 months | Pharmacokinetic Parameters |
| Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Time Point (AUC0-t) | Up to 6 months | Pharmacokinetic Parameters |
| Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | Up to 6 months | Pharmacokinetic Parameters |
| Peripheral Immune-Cell Subsets Change From Baseline | Up to 6 months | Pharmacodynamic Parameters. Change from baseline in peripheral immune-cell subsets, including natural killer cells (CD3-negative/CD56-positive), activated natural killer cells (CD3-negative/CD56-positive/CD69-positive), CD8-positive T cells, and myeloid-derived suppressor cells (CD11b-positive/CD33-positive). |
| Plasma Cytokines and Other Soluble Biomarkers Change From Baseline | Up to 6 months | Change from baseline in plasma concentrations of interferon gamma, perforin, granzyme B, tumour necrosis factor alpha, granulocyte colony-stimulating factor, interleukin-1 beta, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, interleukin-12p70, interleukin-13, and interleukin-17. |
Countries
China
Outcome results
None listed