An Open-label, Phase I/II Study of PLENA Regimen in Patients With Unresectable Pancreatic Cancer or BTC

Study Overview
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Brief Summary
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Immunotherapy of cancer based on PD-1/PD-L1 blockade has prompted a revolution in cancer clinical management, albeit as yet immunotherapy-based treatment approaches in pancreatic cancer and biliary tract cancer (BTC) remain to have proven value, highlights the urgency for designing novel therapeutic strategies to combat these deadly diseases. The immunomodulatory effect of lenvatinib (Lenvatinib is an oral multi-kinase inhibitor) on tumor microenvironments may contribute to antitumor activity of immune checkpoint blockade. This one-arm, phase I/II study is designed to assess the safety and efficacy of the combined regimen of Durvalumab (anti-PD-L1 antibody), Lenvatinib and Paclitaxel albumin (nab-paclitaxel).

Official Title
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A Phase I/II, Open-label, One-arm, Single-center Study to Evaluate the Safety and Efficacy of the PLENA Regimen in Subjects With Unresectable Pancreatic Cancer or Biliary Tract Cancer

Conditions
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Pancreatic Cancer, Biliary Tract Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Lenvatinib
* Drug: Nab paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Subjects must have histologically proven unresectable pancreatic cancer or biliary tract cancer 2.18 to 75 years old. 3.Life expectancy of at least 6 months. 4.Eastern Cooperative Oncology Group performance status 0-2. 5.Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria. 6.Subjects with Anti-PD-1/L1 antibody treatment history are eligible which must be disease progression. 7.Adequate organ function. 8.Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug. Exclusion Criteria: Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications. Serious uncontrolled medical disorders or active infections, pulmonary infection especially. Prior organ allograft. Women who are pregnant or breastfeeding. Women with a positive pregnancy test on enrollment or prior to investigational product administration. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLENA regimen<br>Subject received PLENA regimen every 3 weeks until achieving a second assessable complete response or up to a maximum of 8 cycles. Treatment continued until progressive disease or intolerable toxicity, or withdrawal of consent. | Drug: Durvalumab<br>* Administered intravenously, 1000 mg on day 1 in a 3-week cycle<br>Drug: Lenvatinib<br>* Administered orally, 8mg/d once daily in a 3-week cycle<br>Drug: Nab paclitaxel<br>* Administered intravenously, 180-220 mg/m2 on day1 in a 3-week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects with treatment-related adverse events (AEs) | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit. | 6 months | 
| Object response rate (ORR) | ORR is defined as the proportion of subjects who achieved a partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | DCR is defined as the proportion of subjects who achieved a stable disease (SD), partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 12 months | 
| Progression-free survival (PFS) | PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per the RECIST V1.1. | 12 months | 
| Overall survival (OS) | OS time was measured from the study entry to the date of death. | 24 months | 
| Number of participants with laboratory test abnormalities | The laboratory tests of serum cytokines and chemokines will be performed on day 1 of each cycle, and the abnormality will be determined by the investigator. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lenvatinib, unresectable, anti-PD-L1 antibody, nab-paclitaxel