Plerixafor and Cemiplimab in Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and clinical activity of plerixafor in combination with cemiplimab in patients with metastatic pancreatic cancer.

Official Title
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A Phase 2 Study of Plerixafor and Cemiplimab in Metastatic Pancreatic Cancer

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: Cemiplimab
* Drug: Plerixafor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Have histologically or cytologically-proven ductal pancreatic cancer. Have metastatic disease. Have documented radiographic disease progression after previous systemic chemotherapy given in a neoadjuvant, adjuvant, locally advanced or metastatic setting. Patients with the presence of at least one measurable lesion. Willing to have to a tumor biopsy. Life expectancy of greater than 3 months. Patients must have adequate organ and marrow function defined by study - specified laboratory tests. Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol. Men must use acceptable form of birth control while on study. Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: Known history or evidence of brain metastases. Had chemotherapy, radiation, or steroids within 14 days prior to study treatment. Have received any investigational drugs, a live vaccine, any allergen hyposensitization therapy, growth factors or major surgery within 28 days prior to study treatment. Require any antineoplastic therapy. Had surgery within 28 days of dosing of investigational agent. Has received any prophylactic vaccine within 14 days of first dose of study drug. History of prior treatment with anti-cxcr4. Have used any systemic steroids within 14 days of study treatment. Patients receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin, within 14 days of study drug administration. Hypersensitivity reaction to any monoclonal antibody. Evidence of clinical or radiographic ascites. Have clinically significant and/or malignant pleural effusion. Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Has an active known or suspected autoimmune disease. Prior tissue or organ allograft or allogeneic bone marrow transplantation. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE], version 5) or baseline before administration of study drug. Infection with HIV or hepatitis B or C at screening. Patient has a pulse oximetry of <92% on room air. Patient is on supplemental home oxygen. Has uncontrolled intercurrent acute or chronic medical illness or any use of illicit drugs or substance abuse. Patient is unwilling or unable to follow the study schedule for any reason. Woman who are pregnant or breastfeeding. Have rapidly progressing disease, as judged by the investigator. History of significant, recurrent, unexplained postural hypotension in the last 6 months.

Ages Eligible for Study
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Minimum Age: 18 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: Cemiplimab and Plerixafor<br>All participants will receive Cemiplimab and Plerixafor. | Drug: Cemiplimab<br>* Patients will receive treatment Day 1 of each cycle (21 days) for up to 2 years. Drug: Cemiplimab (350 mg) will be administered IV on day 1 (21 day cycle).<br>* Other names: REGN-2810, Libtayo;Drug: Plerixafor<br>* Patients will receive treatment on the first 7 days of each cycle (21 days) for up to 2 years. Drug: Plerixafor (80mcg/kg/hr) will be administered as a continuous IV infusion of the first 7 days of each cycle (21 days cycle).<br>* Other names: AMD3100, Mozobil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) using immune RECIST (iRECIST) criteria | ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) using RECIST 1.1 criteria | Overall Response Rate (ORR) is the best response recorded from the start of the study treatment until the disease progression/recurrence based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Estimation based on the Kaplan-Meier curve. | 4 years | 
| Number of participants experiencing grade 3 or above drug-related toxicities | When calculating the incidence of adverse events (AEs), each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject. Estimation based on the Kaplan-Meier curve. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plerixafor, Cemiplimab, Immunotherapy, PD-L1 (receptor blocking antibody), Anti-PD-L1, CXCR4 (chemokine receptor), Antibodies, Metastatic pancreatic cancer