KN046 in Subjects With Advanced Pancreatic Ductal Adenocarcinoma.

Study Overview
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Brief Summary
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This study is a multicenter, randomized, double-Blind Phase III Study to compare the clinical efficacy and safety of KN046 plus gemcitabine and nab-paclitaxel versus placebo plus gemcitabine and nab-paclitaxel in subjects with advanced pancreatic ductal adenocarcinoma who have not previously received systemic treatment.

Official Title
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A Multicenter, Randomized, Double-Blind Phase III Study to Assess the Efficacy and Safety of KN046 Combined With Gemcitabine and Nab-Paclitaxel Versus Placebo Combined With Gemcitabine and Nab-Paclitaxel in First Line Advanced Pancreatic Ductal Adenocarcinoma Subjects (ENREACH-PDAC-01).

Conditions
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Advanced Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: KN046
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18, male or female; Has histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC); Has not received prior systemic treatment for their locally advanced or metastatic PDAC; Has presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1); Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status; Has a life expectancy of at least 3 months; Has adequate organ function; If female of childbearing potential, have a negative serum pregnancy test within 7 days prior to first trial treatment; If female of childbearing potential or a male subject with a partner with childbearing potential, be willing to use a highly effective method of contraception (with a failure rate of less than 1.0% per year) from first study treatment to 24 weeks after completion of the trial treatment. Exclusion Criteria: Untreated active CNS metastasis or leptomeningeal metastasis. Is currently participating and receiving an investigational drug or has participated in a study of an investigational drug within 4 weeks or within 5 times of half-life (no less than 2 weeks), whichever is shorter prior to the first dose of trial treatment; Has received other anti-tumor treatment within 4 weeks or within 5 times of half-life (no less than 2 weeks), whichever is shorter prior to the first trial treatment; Major surgery for any reason, except diagnostic biopsy, within 4 weeks of the first administration of trial treatment and/or if the subject has not fully recovered from the surgery within 4 weeks of the first administration of trial treatment; Curative radiation within 3 months of the first dose of trial treatment. Radiation to more than 30% of the bone marrow or with a wide field of radiation should not be used within 4 weeks prior to the first administration of trial treatment; Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement doses, equivalent to < 10 mg prednisone daily, inhaled steroids and topical use of steroids); Vaccination within 28 days of the first administration of trial treatment, except for administration of inactivated vaccines (e.g., inactivated influenza vaccines); Has interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management; History or current active autoimmune disease that might deteriorate when receiving an immunostimulatory agent； Previous malignant disease History of uncontrolled intercurrent illness Prior therapy with any antibody/drug targeting T cell coregulatory proteins Known severe hypersensitivity reactions to antibody drug； Is pregnant or breastfeeding; Other medical conditions that at the discretion of investigator interfere with the requirements of the trial in terms of safety or efficacy evaluation, or treatment compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm<br> | Drug: KN046<br>* KN046+Nab-Paclitaxel+Gemcitabine In combine therapy stage, KN046 is 5 milligram per kilogram, every 2 weeks. In maintain stage, KN046 is 5 milligram per kilogram, every 2 weeks.<br>|
| Placebo Comparator: Control arm<br> | Drug: placebo<br>* placebo+Nab-Paclitaxel+Gemcitabine In combine therapy stage, placebo is 5 milligram per kilogram, every 2 weeks. In maintain stage, placebo is 5 milligram per kilogram, every 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Time between randomization to date of disease progression or death due to any cause. | up to 2 years | 
| Overall response rate (ORR) | Complete Response or Partial Response according to RECIST | up to 2 years |