Overview

The first in human clinical study is planned as an open-label, dose-escalation, and dose-expansion, multicentre, two-part, Phase 1/2a study of PBP1510 administered to patients with advanced/metastatic pancreatic cancer. The study will be conducted in two parts, Part 1 as a PBP1510 single agent dose-escalation, and PBP1510 dose-escalation in combination with gemcitabine, and Part 2 as PBP1510 dose-expansion at the RP2D in combination with gemcitabine.

Eligibility

Inclusion Criteria:

        Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) must meet all of the
        following inclusion criteria:
          1. Adults ≥ 18 years of age (or the legal age of majority in the country of recruitment)
             at the time consent is obtained.
          2. Patient should understand, voluntarily sign, and date the written consent form prior
             to any protocol-specific procedures.
          3. Performance Status score less than or equal to 1 according to the Eastern Cooperative
             Oncology Group (ECOG) scale.
          4. Have histological or cytological evidence of a diagnosis of pancreatic cancer that is
             advanced and/or metastatic.
          5. Have a life expectancy of ≥ 3 months.
          6. No other malignancy present that would interfere with the current intervention.
          7. Prior radiation therapy for treatment of cancer is allowed to < 25% of the bone
             marrow, and patients must have recovered from the acute toxic effects of their
             treatment prior to study enrolment. Prior radiotherapy must be completed at least 4
             weeks before the first dose of study treatment.
          8. At least one measurable lesion as per RECIST v1.1
          9. Adequate baseline organ function defined as:
             ANC ≥ 1.5 × 10^9 /L; Haemoglobin ≥ 9 g/dL; Platelets ≥ 100 × 10^9 /L; Total bilirubin
             ≤ 2 × ULN (≤ 3 x ULN for patients with biliary stenting and patients with Gilbert's
             syndrome); AST and ALT < 3 x ULN (≤ 5 x ULN for patients with hepatic metastases);
             Serum creatinine OR creatinine clearance (as determined by the Cockcroft Gault
             formula) OR eGFR based on MDRD ≤ 1.5 x ULN OR ≥ 50 mL/min OR ≥ 50 mL/min/1.73 m^2;
             LVEF ≥ 50% by ECHO or MUGA; QTc ≤ 470 ms
         10. Female patients of nonchildbearing potential must meet at least 1 of the following
             criteria: have undergone a documented hysterectomy, and/or bilateral oophorectomy;
             have medically confirmed ovarian failure or achieved postmenopausal status. A
             postmenopausal state is defined as cessation of regular menses for at least 12
             consecutive months with no alternative pathological or physiological cause and have a
             follicle stimulating hormone (FSH) level confirming the postmenopausal state in women
             not using hormonal contraception or hormonal replacement therapy. Female patients of
             childbearing potential must have a negative serum pregnancy test within 28 days prior
             to and negative urine pregnancy test just prior to the first dose of PBP1510 and agree
             to use effective contraception, in accordance with the recommendations of the Clinical
             Trials Facilitation and Coordination Group (CTFG) from study entry and until for at
             least 6 months after the last dose of PBP1510.
         11. For women of childbearing potential and men with partners of childbearing potential,
             agreement (by patient and/or partner) to use two effective forms of contraception
             (e.g., surgical sterilization, a reliable barrier method, birth control pills, or
             contraceptive hormone implants) from study entry and until for at least 6 months after
             the last dose of PBP1510.
             Investigator or his/her representative should discuss acceptable pregnancy prevention
             method(s) with the patients. Highly effective methods of birth control include those
             that result in a low failure rate (i.e., less than 1% per year) when used consistently
             and correctly, such as implants, injectables, combined oral contraceptives,
             levonorgestrel-releasing intrauterine system, intra-uterine devices (IUDs), and true
             sexual abstinence.
         12. Patients must be willing and able to comply with scheduled visits, treatment plan,
             study restrictions, laboratory tests, contraceptive guidelines, and other study
             procedures.
             Patients enrolling into Part 1 (Phase 1) of the study must also meet the following
             inclusion criteria:
         13. Monotherapy and combination cohorts: advanced/metastatic pancreatic cancer patients
             whose tumours have progressed after at least one prior line of standard chemotherapy.
             Patients enrolling into Part 2 (Phase 2a) of the study must also meet the following
             inclusion criteria:
         14. Advanced/metastatic pancreatic cancer patients whose tumours have progressed after one
             prior line of standard chemotherapy.
        Exclusion Criteria:
        Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) will be excluded if any of
        the following criteria apply:
          1. Patients who have known brain metastases will be excluded from the study. However, a
             patient may be included in the study, if has been previously treated for brain
             metastasis, the disease is well controlled for at least 3 months, and the patient is
             off steroids.
          2. Patients who have undergone a major surgery within 4 weeks prior to the start of
             PBP1510 administration, other than endoscopic/radiation procedures, bypass surgery
             (i.e., gastrojejunostomy), laparoscopy, port placement or a diagnostic surgery (i.e.,
             surgery done to obtain a diagnostic biopsy, without removal of an organ), as long as
             the patient has recovered from these minor surgical procedures.
          3. Patients who have active, uncontrolled bacterial, viral, or fungal infection(s)
             requiring systemic therapy, e.g., an active opportunistic infection with mycobacteria,
             cytomegalovirus, toxoplasma, Pneumocystis carinii (P. carinii), or other
             microorganisms that is under treatment with myelotoxic drugs.
          4. Patient has a known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
          5. Patient has known history of or currently active hepatitis B (e.g., hepatitis B
             antigen [HBsAg] reactive), hepatitis C (e.g., HCV RNA [qualitative] is detected) or
             syphilis [Venereal Disease Research Laboratory (VDRL) to detect antibodies in blood]).
          6. Patient has impaired cardiac function and uncontrolled cardiac diseases/hypertension
             that are deemed clinically significant by the Investigator and which could compromise
             the patient's safety or the study data integrity.
          7. Patient has serious psychiatric disorders, which could compromise the patient's safety
             or the study data integrity.
          8. Any other malignancy from which the patient has been disease-free for less than 5
             years, except for adequately treated and cured basal or squamous cell skin cancer.
          9. Patients who are enrolled in any other therapeutic clinical trial.
         10. Patients currently receiving radiation therapy or those having received radiation
             within 4 weeks prior to study entry.
         11. Patients having received investigational anti-cancer drug within 28 days (or 5
             half-lives, whichever is longer) preceding the first dose of PBP1510 or chemotherapy
             within the last 4 weeks prior to the first dose of PBP1510.
         12. Patients with known allergy or hypersensitivity to components of the PBP1510
             formulation including the excipients and history of hypersensitivity to Chinese
             hamster ovary cell products or other recombinant human or humanized antibodies.
         13. Patients who are pregnant, or breast feeding.
         14. Patients who are unwilling or unable to comply with study procedures.
         15. Patients who are not eligible to participate in this study, as judged by
             Investigators.
         16. A history of allergic reactions attributed to gemcitabine or compounds of similar
             chemical composition to gemcitabine and/or previous treatment discontinuation due to
             gemcitabine toxicity.
        Note: Patients with previous exposure to gemcitabine should not be excluded from the study.