A Maintenance Therapy Study of Odetiglucan With CDX-1140 in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

NCT05484011 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PGG-PAN2111
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this maintenance therapy study is to identify the maximum tolerated dose (MTD) and/ or recommended Phase 2 dose (RP2D), and evaluate the safety, tolerability, and dose-limiting toxicities (DLTs) of odetiglucan in combination with CDX-1140 in patients with metastatic PDAC with evidence of response or stable disease following a minimum of 16 and no more than 32 weeks of chemotherapy. Up to 45 patients will be enrolled and dosed (30 patients in Part A and 15 in Part B).

Conditions

Metastatic Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Determination of MTD of odetiglucan + CDX-1140

  Within 24 months of last patient enrolled

Secondary Outcomes (4)

• Duration of Response

  Within 24 months of last patient enrolled

• Overall Response Rate

  Within 24 months of last patient

• Median Progression Free Survival and Progression Free Survival at 6 Months

  Within 36 months of last patient enrolled

• Median Overall Survival and Overall Survival at 1 Year

  Within 36 months of last patient enrolled

Study Arms (2)

Part A

EXPERIMENTAL

Patients will have regularly scheduled study visits on days 1, 8, and 15 of each cycle. On Day 1 patients will receive odetiglucan and CDX-1140. On Days 8 \& 15 only odetiglucan. Additional study visits may be required during some cycles for safety, efficacy, and translational assessments. Patients will dose to confirmed progression, a safety event or other administrative reason requiring discontinuation; all patients are allowed to dose up to 2 years (patients continuing to derive benefit may stay on treatment longer following consultation between Investigator and Sponsor). Following discontinuation patients will be followed up to 1 year.

Biological: odetiglucan; Biological: CDX-1140

Part B

EXPERIMENTAL

Patients will have regularly scheduled study visits on day 1 of each cycle. On Day 1 patients will receive odetiglucan and CDA-1140. Additional study visits may be required during some cycles for safety, efficacy, and translational assessments. Patients will dose to confirmed progression, a safety event or other administrative reason requiring discontinuation; all patients are allowed to dose up to 2 years (patients continuing to derive benefit may stay on treatment longer following consultation between Investigator and Sponsor). Following discontinuation patients will be followed up to 1 year.

Biological: odetiglucan; Biological: CDX-1140

Interventions

odetiglucan BIOLOGICAL

Odetiglucan is a soluble, β-1,3/1,6 glucan isolated from the cell wall of a proprietary Saccharomyces cerevisiae yeast strain. Odetiglucan acts as a Pathogen-Associated Molecular Pattern (PAMP).

Also known as: Imprime, BTH-1677, Imprime PGG

Part A; Part B

CDX-1140 BIOLOGICAL

A fully human agonist anti-CD40 monoclonal antibody

Part A; Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be age 18 years or older and has read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures.
• Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with metastatic disease.
• Agree to be tested for peripheral blood levels of IgG anti-beta-glucan antibody (ABA) as determined by an ELISA test prior to start of study treatment.
• Have received a minimum of 16 weeks and no more than 32 weeks of therapy (first-line chemotherapy) and experienced a CR, PR, or SD with no evidence of progression immediately before enrollment (within 14 days of first dose).
• a. Note: this requires at least durable stability or a reduction in tumor size by imaging. If a patient has demonstrated an imaging response to chemotherapy and has not progressed but had to discontinue chemotherapy prior to 16-32 weeks for a legitimate medical reason (as determined by the investigator), the patient may still be considered for the trial.
• Have resolution of all chemotherapy-related toxicities to pre-treatment levels with exception of alopecia (which can be ongoing) and neuropathy (which can be ≤ Grade 2).
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of screening.
• Have the following laboratory values, without transfusions or growth factors, at Screening and within 14 days of the first dose of investigational agents:
• White blood cell count ≥2000/uL
• Absolute neutrophil count (ANC) ≥1.5 x 109/L.
• Platelet count ≥100 x 109/L.
• Hemoglobin ≥9 g/dL.
• Serum creatinine ≤1.5 mg/dL, and creatinine clearance ≥50 ml/min as measured by Cockcroft and Gault formula.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x institution's ULN for patients with no concurrent liver metastases, OR ≤5.0 x institution's ULN for patients with concurrent liver metastases.
• Total bilirubin ≤1.5 x ULN, except in patients with documented Gilbert's Syndrome who must have a total bilirubin ≤3 x ULN.

You may not qualify if:

• Previous exposure to odetiglucan (Imprime PGG).
• Previous exposure to CD40 antibodies or any other immunomodulatory agent for the treatment of cancer.
• Received chemotherapy within the 14 days prior to initiation of study treatment.
• a. Concomitant antineoplastic systemic chemotherapy or biological therapy is not allowed.
• A history of (non-infectious) pneumonitis / interstitial lung disease or has current pneumonitis / interstitial lung disease including grade 1 asymptomatic pneumonitis noted on imaging not requiring treatment.
• Had any active or inactive autoimmune disease or syndrome (i.e., rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• a. Note: Exceptions include patients with vitiligo or resolved childhood asthma/atopy, hypothyroidism stable on hormone replacement, controlled asthma, Type I diabetes, Graves' disease, or Hashimoto's disease, or with medical monitor approval.
• An uncontrolled concurrent illness, including an ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, interstitial lung disease or uncontrolled diabetes.
• QT interval corrected for heart rate using Fridericia's (QTcF) method \>450 msec for males and \>460 msec for females.
• A history of myocardial infarction within 6 months or a history of arterial thromboembolic event within 3 months of the first dose of investigational agent.
• A history of human immunodeficiency virus (HIV), hepatitis B (HB), or hepatitis C, except for the following:
• Patients with anti-HB core antibody but with undetectable HB virus deoxyribonucleic acid (DNA) and negative for HB surface antigen
• Patients with resolved or treated hepatitis C virus (HCV) (i.e., HCV antibody positive but undetectable HCV RNA).
• Received concurrent or prior use of an immunosuppressive agent within 14 days of the first dose of investigational agent, with the following exceptions and notes:
• Systemic steroids at physiologic doses (equivalent to dose of 10 mg oral prednisone) are permitted.

Sponsors & Collaborators

• HiberCell, Inc.: lead
• Celldex Therapeutics: collaborator

Study Sites (4)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

BTH1677

Study Officials

• Mark O'Hara

  University of Pennsylvania

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3 + 3 de-escalation design

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: August 2, 2022
• Study Start: December 15, 2022
• Primary Completion: March 4, 2024
• Study Completion: March 4, 2024
• Last Updated: April 10, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)