ANTI-(PANCREATIC ADENOCARCINOMA UPREGULATED FACTOR) IGG1 HUMANISED MONOCLONAL ANTIBODY for Advanced/metastatic pancreatic adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Adults ≥ 18 years of age (or the legal age of majority in the country of recruitment) at the time consent is obtained."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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, intrauterine devices (IUD), and true sexual abstinence."}
• {"criterion_text":"- Patients must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures."}
• {"criterion_text":"- Patients enrolling into Part 1 (Phase 1) of the study must also meet the following inclusion criteria: Monotherapy and combination cohorts: advanced/metastatic pancreatic cancer patients whose tumours have progressed after at least one prior line of standard chemotherapy."}
• {"criterion_text":"- Patients enrolling into Part 2 (Phase 2a) of the study must also meet the following inclusion criteria: Advanced/metastatic pancreatic cancer patients whose tumours have progressed after one prior line of standard chemotherapy."}
• {"criterion_text":"- Patient should understand, voluntarily sign, and date the written consent form prior to any protocol-specific procedures."}
• {"criterion_text":"- Performance Status score less than or equal to 1 according to the Eastern Cooperative Oncology Group (ECOG) scale."}
• {"criterion_text":"- Have histological or cytological evidence of a diagnosis of pancreatic adenocarcinoma that is advanced and/or metastatic."}
• {"criterion_text":"- Have a life expectancy of ≥ 3 months."}
• {"criterion_text":"- At least one measurable lesion as per RECIST v1.1."}
• {"criterion_text":"- Adequate baseline organ function defined as: a) ANC: ≥ 1.5 × 10^9 /L; b) Haemoglobin: ≥ 9 g/dL; c) Platelets: ≥ 100 × 10^9 /L; d) Total bilirubin: ≤ 2 × ULN (≤ 3 x ULN for patients with biliary stenting and patients with Gilbert’s syndrome); e) AST and ALT: < 3 x ULN (≤ 5 x ULN for patients with hepatic metastases); f) Creatine clearance (as determined by the Cockcroft Gault formula): ≥ 50 mL/min; g) LVEF: ≥ 50% by ECHO or MUGA; h) QTc: ≤ 470 ms"}

Exclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients who have undergone a major surgery within 4 weeks prior to the start of PBP1510 administration."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patient has a known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies)."}
• {"criterion_text":"- Patient currently has active hepatitis B, hepatitis C, or syphilis."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patient has serious psychiatric disorders, which could compromise the patient’s safety or the study data integrity."}
• {"criterion_text":"- Any other malignancy from which the patient has been disease-free for less than 2 years, except for adequately treated and cured basal or squamous cell skin cancer."}
• {"criterion_text":"- Patients who are enrolled in any other therapeutic clinical trial, unless they have confirmed disease progression in the trial and area in follow-up."}
• {"criterion_text":"- Patients currently receiving radiation therapy or those having received radiation within 2 weeks prior to first dose of PBP1510. Patients must have recovered from the toxic effects of their treatment prior to first dose of study drug."}
• {"criterion_text":"- Patients having received investigational anti-cancer drug within 28 days (or 5 half-lives, whichever is shorter) preceding the first dose of PBP1510 or chemotherapy within the last 2 weeks prior to the first dose of PBP1510. Patients must have recovered from the toxic effects of their treatment prior to first dose of study drug."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients who are pregnant, or breast feeding."}
• {"criterion_text":"- Patients who are unwilling or unable to comply with study procedures."}
• {"criterion_text":"- Patients who are not eligible to participate in this study, as judged by Investigators."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Part 1 (Phase 1): Safety parameters including AEs, SAEs, DLTs, clinical laboratory values (haematology and blood chemistry), vital signs, and ECG assessments in patients, after receiving PBP1510 administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Measured by recording adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), clinical laboratory values (haematology and blood chemistry), vital signs, and ECG assessments."}
• {"endpoint_text":"- Part 2 (Phase 2a): Safety parameters including AEs, SAEs, clinical laboratory values (haematology and blood chemistry), vital signs, and ECG assessments in patients, after receiving PBP1510 administered at the RP2D in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Measured by recording AEs, SAEs, clinical laboratory values (haematology and blood chemistry), vital signs, and ECG assessments at scheduled visits following administration at RP2D in combination with gemcitabine."}
• {"endpoint_text":"- Part 2 (Phase 2a): ORR (rate of patient with complete response [CR] or partial response [PR]) evaluated by Response Evaluation Criteria in Solid Tumours version v1.1 (RECIST v1.1), after receiving 4 cycles of PBP1510 administered at the RP2D in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Objective response rate (ORR) assessed per RECIST v1.1 after 4 cycles; CR or PR determined by radiologic assessment per RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Part 1 (Phase 1): Cmax, Tmax, t1/2, AUC, MRT, Vss, Vc and CL of PBP1510 administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Pharmacokinetic parameters (Cmax, Tmax, t1/2, AUC, MRT, Vss, Vc, CL) measured from blood samples following IV administration of PBP1510."}
• {"endpoint_text":"- Part 1 (Phase 1): Cmax, Tmax, t1/2, AUC, MRT, and CL of gemcitabine administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Pharmacokinetic parameters of gemcitabine measured from blood samples when administered in combination with PBP1510."}
• {"endpoint_text":"- Part 1 (Phase 1): Presence of ADA and NAb against PBP1510 administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Immunogenicity assessed by measuring anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against PBP1510."}
• {"endpoint_text":"- Part 1 (Phase 1) - Exploratory: Preliminary evidence of clinical outcomes as assessed by ORR after treatment with PBP1510 administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Preliminary ORR assessed per RECIST v1.1."}
• {"endpoint_text":"- Part 1 (Phase 1) - Exploratory: Analysis of PAUF in tumour tissue pre-treatment and after treatment with PBP1510 administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"PAUF expression analysed in tumour tissue pre- and post-treatment (methodology as per protocol tissue analysis)."}
• {"endpoint_text":"- Part 2 (Phase 2a): Ctrough, Cmax, Tmax, t1/2, AUC, MRT, Vss, Vc and CL of PBP1510 administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"PK parameters for PBP1510 measured in combination therapy from blood samples."}
• {"endpoint_text":"- Part 2 (Phase 2a): Ctrough, Cmax, Tmax, t1/2, AUC, MRT, and CL of gemcitabine administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"PK parameters for gemcitabine measured when co-administered with PBP1510."}
• {"endpoint_text":"- Part 2 (Phase 2a): PFS, OS, and DoR after treatment with PBP1510 administered in combination with gemcitabine in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Progression-free survival (PFS), overall survival (OS), and duration of response (DoR) assessed by scheduled follow-up and RECIST v1.1 assessments."}
• {"endpoint_text":"- Part 2 (Phase 2a): Presence of ADA and NAb against PBP1510 administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Immunogenicity assessment for ADA and NAb in combination therapy."}
• {"endpoint_text":"- Part 2 (Phase 2a) - Exploratory: Pre-treatment PAUF expression and clinical efficacy outcome after treatment with PBP1510 administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"Correlation analysis between pre-treatment PAUF expression and clinical efficacy outcomes."}
• {"endpoint_text":"- Part 2 (Phase 2a) - Exploratory: Analysis of PAUF in tumour tissue pre-treatment and after treatment with PBP1510 administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.","definition_or_measurement_approach":"PAUF expression analysis in tumour tissue before and after treatment."}

Spain

Earliest CTIS Part Ii Submission Date

07-05-2024

Latest Decision Or Authorization Date

11-07-2025

Processing Time Days

430

Number Of Sites

2

Number Of Participants

38

Primary sponsor

Full Name

Prestige Biopharma Ltd

Organisation Type

Pharmaceutical company

Country Of Registered Address

Singapore