Evaluating GP-2250 with Gemcitabine for Advanced Pancreatic Cancer

Phase 1 Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GP-2250 With Gemcitabine in Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma Following Progression on 5-FU-based Chemotherapy

This study is testing a new drug called GP-2250 combined with gemcitabine to see if it is safe and works well for people with advanced pancreatic cancer who have already been treated with other chemotherapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Geistlich Pharma AG (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 5 sites (Newport Beach, California and 4 other locations)
• Trial ID: NCT03854110 on ClinicalTrials.gov

What this trial studies

This phase 1 trial investigates the safety and tolerability of GP-2250 in combination with gemcitabine for patients with advanced pancreatic cancer who have previously undergone treatment with 5-fluorouracil-based chemotherapy. The study employs a Bayesian Optimal Interval (BOIN) dose escalation design for initial cohorts, transitioning to a 3+3 dose escalation design for subsequent cohorts. Participants will receive treatment until disease progression or unacceptable toxicity occurs, with assessments based on RECIST V1.1 criteria. The trial aims to determine the optimal dosing and safety profile of this combination therapy.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with advanced unresectable or metastatic pancreatic adenocarcinoma who have progressed on prior 5-fluorouracil-based chemotherapy.

Not a fit: Patients with resectable pancreatic cancer or those who have not received prior 5-fluorouracil-based chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced pancreatic cancer.

How similar studies have performed: While this approach is novel in its specific combination, similar studies have shown promise in treating pancreatic cancer with combination therapies.

Eligibility criteria

Inclusion Criteria:

Informed Consent:

1. Capable of giving signed informed consent as described in Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Male and female subjects age \> 18 years at the time of trial entry. Type of Subject and Disease Characteristics
3. Histologically or cytologically confirmed advanced unresectable or metastatic pancreatic adenocarcinoma
4. Subjects should be eligible to receive gemcitabine monotherapy for the treatment of their pancreatic cancer per the judgment of the Investigator
5. Subjects must have documented disease progression while receiving or within 3 months of completing prior treatment with 5-fluorouracil-based chemotherapy.
6. Subjects must have at least one RECIST Version 1.1 defined measurable tumor lesion
7. Subjects must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
8. Subjects with known central nervous system metastasis must have undergone brain targeted treatment and must be asymptomatic or radiographically and clinically stable (including not requiring steroids or anti-seizure medications) for at least 4 weeks prior to enrollment.
9. All subjects must consent to provide archived tumor specimens for biomarker studies.
10. Subjects must have adequate organ function as indicated by the following laboratory values:

    1. Absolute neutrophil count (ANC) ≥ 1,500 /mL
    2. Platelets ≥ 100,000 / mL
    3. Hemoglobin ≥ 9 g/dL
    4. Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
    5. Serum total bilirubin ≤ 1.5 × ULN
    6. Aspartate aminotransferase (AST), (Serum glutamic oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT), and (Serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × ULN OR ≤ 5 × ULN for subjects with liver metastasis
    7. International Normalized Ratio (INR) and/or Prothrombin Time (PT) ≤ 1.5 × ULN
    8. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN
    9. Serum Albumin ≥ 3 gm/dL
11. Female subjects of childbearing potential (woman of childbearing potential \[WOCBP\]) must have a negative serum pregnancy test.
12. Subjects must use adequate contraception for the duration of the trial:

    1. Male subjects must agree to use a highly effective contraception during the treatment period and for at least 3 months after the last dose of trial intervention and refrain from donating sperm during this period
    2. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a WOCBP OR a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of trial intervention.

Exclusion Criteria:

1. Diagnosis of any active malignancy other than pancreatic cancer within the past 2 years (not including non-melanoma skin carcinoma, ductal carcinoma in situ of the breast, or carcinoma in situ of uterine cervix treated with curative intent).
2. Subjects has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonia or multiple allergies, clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome with \<=6 months prior to the start of study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or ascites requiring paracentesis in the 4 weeks prior to Screening.
3. Any other medical, psychiatric, or social condition deemed by the Investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate and participate in the trial, or which would interfere with the interpretation of the results.
4. Subject has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
5. Prior history or current signs of hyphema or glaucoma.
6. History of sickle cell disease or hereditary non-spherocytic hemolytic anemia.
7. Baseline QTc interval \>480 msec for female subjects or \>450 msec for male subjects.
8. Subject is unwilling or unable to comply with study procedures or is planning to take a vacation for 7 or more consecutive days during the source of the study.
9. First degree relative of the investigator, study staff or the sponsor.
10. Positive test for SARS-CoV2 (COVID-19) by polymerase chain reaction (PCR) testing within one week prior to Screening.
11. Any chemotherapy administered within 3 weeks or 5 half-lives (whichever is shorter) before first dose of GP-2250; other anti-cancer therapy (including surgery, radiotherapy, immunotherapy, hormone therapy, or targeted therapy) administered within 4 weeks or 5 half-lives (whichever is shorter) before the first dose of GP-2250; or within 6 weeks in the case of certain therapies (mitomycin C and nitrosoureas).

    Prior/Concurrent Clinical Trial Experience:
12. Investigational therapy administered within 4 weeks or 5-half lives (whichever is shorter) before the first dose of GP-2250.

Where this trial is running

Newport Beach, California and 4 other locations

• Hoag Family Cancer Institute — Newport Beach, California, United States (Recruiting)
• University of Kansas Cancer Center — Fairway, Kansas, United States (Recruiting)
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (Recruiting)
• Wake Forest Baptist Health — Winston-Salem, North Carolina, United States (Recruiting)
• Abramson Cancer Center at the University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Study coordinator: James C Costin, MD

Conditions Pancreatic Cancer, Adult; Advanced disease; 5-fluorouracil