First in Human Phase1/2a Clinical Trial of Anti-PAUF Monoclonal Antibody PBP1510 in Patients With Pancreatic Cancer

NCT ID: NCT05141149

Last Updated: 2025-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-05

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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The first in human clinical study is planned as an open-label, multicentre, two-part, Phase 1/2a study to assess the safety, pharmacokinetics, and efficacy of PBP1510 in patients with advanced/metastatic pancreatic cancer. Part 1 (Phase 1) is a dose-escalation phase, wherein PBP1510 will be administered, as monotherapy (monotherapy cohorts) or in combination with gemcitabine (combination cohorts) in advanced/metastatic pancreatic cancer patients whose tumours have progressed on at least one previous line of chemotherapy for locally advanced/metastatic disease. The RP2D will be selected based on the analysis of the PK, safety, and efficacy data. Part 2 (Phase 2a) will be an open-label study and patients will be administered the RP2D of PBP1510 derived from Part 1, in combination with gemcitabine for advanced/metastatic pancreatic cancer patients whose tumour has progressed on one previous line of chemotherapy for locally advanced/metastatic disease.

Conditions

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Pancreatic Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1M

1 mg/kg of PBP1510 as monotherapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Cohort 1C

1 mg/kg of PBP1510 and 1000 mg/m\^2 of gemcitabine as combination therapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Gemcitabine (1000 mg/m^2)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion in combination with 1000 mg/m2 gemcitabine administered as a 30-minute intravenous infusion.

Cohort 2M

3 mg/kg of PBP1510 as monotherapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Cohort 2C

3 mg/kg of PBP1510 and 1000 mg/m\^2 of gemcitabine as combination therapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Gemcitabine (1000 mg/m^2)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion in combination with 1000 mg/m2 gemcitabine administered as a 30-minute intravenous infusion.

Cohort 3M

6 mg/kg of PBP1510 as monotherapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Cohort 3C

6 mg/kg of PBP1510 and 1000 mg/m\^2 of gemcitabine as combination therapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Gemcitabine (1000 mg/m^2)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion in combination with 1000 mg/m2 gemcitabine administered as a 30-minute intravenous infusion.

Cohort 4M

10 mg/kg of PBP1510 as monotherapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Cohort 4C

10 mg/kg of PBP1510 and 1000 mg/m\^2 of gemcitabine as combination therapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Gemcitabine (1000 mg/m^2)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion in combination with 1000 mg/m2 gemcitabine administered as a 30-minute intravenous infusion.

Cohort 5M

15 mg/kg of PBP1510 as monotherapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Cohort 5C

15 mg/kg of PBP1510 and 1000 mg/m\^2 of gemcitabine as combination therapy will be administered

Group Type EXPERIMENTAL

PBP1510 (400mg/16mL)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Gemcitabine (1000 mg/m^2)

Intervention Type DRUG

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion in combination with 1000 mg/m2 gemcitabine administered as a 30-minute intravenous infusion.

Interventions

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PBP1510 (400mg/16mL)

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion

Intervention Type DRUG

Gemcitabine (1000 mg/m^2)

Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion in combination with 1000 mg/m2 gemcitabine administered as a 30-minute intravenous infusion.

Intervention Type DRUG

Eligibility Criteria

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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.

13. Monotherapy and combination cohorts: advanced/metastatic pancreatic cancer patients whose tumours have progressed after at least one prior line of standard chemotherapy.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prestige Biopharma Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Northwell Health / R.J. Zuckerberg Cancer Center

New Hyde Park, New York, United States

Site Status RECRUITING

Monash Health

Melbourne, , Australia

Site Status RECRUITING

National Cancer Centre Singapore

Singapore, , Singapore

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, Spain

Site Status RECRUITING

Countries

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United States Australia Singapore Spain

Central Contacts

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Mei Li Lim

Role: CONTACT

+65-6924-6535

Fang Ting Pan

Role: CONTACT

+65-6924-6535

Facility Contacts

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Jenna Battaglia

Role: primary

Penny Macquire

Role: primary

+61 0474 769 510

Mui Leng Goh

Role: primary

+65 6436 8000

Jaime Feliu, MD PhD

Role: primary

+34917277516

Other Identifiers

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2024-514379-16-00

Identifier Type: CTIS

Identifier Source: secondary_id

2021-000682-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PAUF-I

Identifier Type: -

Identifier Source: org_study_id

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