(PM-01) IMPRIME PGG® With BTH1704 and Gemcitabine for Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This Phase Ib dose escalation study will evaluate BTH1704, a monoclonal antibody that targets an aberrantly glycosylated antigen Mucin 1, and Imprime PGG, a glucan contained in yeast that is essential in triggering a leukocyte-mediated cytotoxic response towards tumor cells, in combination with gemcitabine in patients with advanced PDAC. The three intravenous drugs are taken in tandem 4 times in a 28-day cycle. The MAD of BTH1704 (BTH, 3 dose levels) in combination with gemcitabine (Gem) and Imprime PGG (I) will be determined using a standard 3+3 design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.

Official Title
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PM-01: Phase 1b Study of PGG Beta Glucan (Imprime PGG®) in Combination With Anti-MUC1 Antibody (BTH1704) and Gemcitabine (Gemzar®) for the Treatment of Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: BTH1704
* Drug: IMPRIME PGG
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years Histologically or cytologically confirmed adenocarcinoma of the pancreas, including pancreatic adenosquamous carcinoma, pancreatic anaplastic adenocarcinoma, pancreatic signet ring carcinoma, papillary mucinous carcinoma, acinar cell carcinoma, and ampulla of vater carcinoma,that is locally advanced (not able to proceed with surgery), recurrent, or metastatic (mixed adenocarcinoma of the pancreas is acceptable where the invasive component is predominantly adenocarcinoma) Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1 Has an ECOG PS of 0, 1, or 2 Has been off chemotherapy for > or = 2 weeks Has a patent biliary stent if required for biliary ductal obstruction, has adequate nutritional intake, and pain which is stable for a minimum of 24 hrs (pain score ≤ 3/10) Has total bilirubin < 2 mg/dL, AST and ALT < 3.0 × ULN or < 5 x ULN for subjects with known hepatic metastases Has serum creatinine < 2.5 × ULN Has hemoglobin ≥ 9 g/dL, ANC ≥ 1.0 × 10^9/L, and platelet count ≥ 100 × 10^9/L Must be willing and able to comply with study Has read, understood and signed the ICF Women of childbearing potential must not be pregnant or breast-feeding. In addition, a medically acceptable method of birth control must be used or total abstinence. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP. Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male patients with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms at least 30 days after the last dose of study drug. Total abstinence is an acceptable alternative. Prior systemic treatments for metastatic disease are permitted, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy, or investigational therapy. Availability of tissue if applicable (from the primary tumor or metastases)for banking Willingness to donate blood for biomarker studies Must have received at least one prior systemic chemotherapy on which disease progressed Exclusion Criteria: Has a diagnosis of resectable pancreatic adenocarcinoma Had surgery within 4 weeks prior to study treatment Has either untreated or symptomatic CNS mets Has a known hypersensitivity to BTH1704, murine proteins, or any component of BTH1704 Has a known hypersensitivity to baker's yeast Has had previous exposure to Imprime PGG Has previously received an organ or progenitor/stem cell transplant Has a history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment Has a known history of HIV positivity or untreated & uncontrolled hepatitis B or C Has any clinically significant infection Has any other severe, uncontrolled medical condition, including uncontrolled DM or unstable CHF or has a known or suspected allergy to the study drug Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation Presence of any non-healing wound, fracture, or ulcer Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance Has any mental or medical condition that prevents the patient from giving informed consent Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to gemcitabine or drugs to formulate.

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: IMPRIME PGG, BTH1704, & Gemcitabine<br>Imprime PGG with BTH1704 at assigned doses administered on days 1, 8, 15, and 22 of a 28-day cycle with Gemcitabine on days 1, 8, and 15, at assigned doses, of a 28-day cycle. | Drug: BTH1704<br>* BTH1704 at assigned doses administered on days 1, 8, 15, and 22 of a 28-day (4 week) cycle.<br>* Other names: Therex;Drug: IMPRIME PGG<br>* Imprime PGG at assigned doses administered on days 1, 8, 15, and 22 of a 28-day (4 week) cycle.<br>* Other names: Beta 1,3/1,6 glucan;Drug: Gemcitabine<br>* Gemcitabine on days 1, 8, and 15, at assigned doses, of a 28-day (4 week) cycle.<br>* Other names: Gemzar®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | The primary objective of this Phase 1b study is to determine the maximal administered dose (MAD) of BTH1704 (Mucin-1 targeted antibody) in combination with gemcitabine and Imprime PGG (beta 1,3/1,6 glucan) when given to patients with advanced and previously treated pancreatic ductal adenocarcinoma (PDAC). | Up to 30 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Effects | Characterize adverse effects (AE) of I-BTH-Gem in patients with advanced PDAC in the second and third line setting. | Up to 30 days post final dose | 
| Disease Response based on RECIST Criteria | Evaluate clinical response of I-BTH-Gem in patients with advanced PDAC in the second and third line setting (RECIST v 1.1). | Up to 8 weeks following final dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, adenocarcinoma of the pancreas (PDAC), mixed adenocarcinoma of the pancreas, locally advanced, recurrent, metastatic