A first-in-human clinical study of PBP1510 in patients with pancreatic cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prestige Biopharma Ltd

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Apr 2023 → ongoing

Decision date (initial)

2024-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-514379-16-00

EudraCT number

2021-000682-32

ClinicalTrials.gov

NCT05141149

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Pharmacodynamic

Part 1 (Phase 1): To evaluate the safety and tolerability of PBP1510 administered as monotherapy, and in combination with gemcitabine, following intravenous (IV) administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.

Part 2 (Phase 2a): To establish the safety and assess the efficacy 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.

Secondary objectives 11

1. Part 1 (Phase 1): To determine the recommended Phase 2a dose (RP2D) of PBP1510.
2. Part 1 (Phase 1): To characterize the PK 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.
3. Part 1 (Phase 1): To characterize the PK 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.
4. Part 1 (Phase 1): To evaluate the immunogenicity 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.
5. Part 1 (Phase 1) - Exploratory: To explore the preliminary clinical outcomes 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.
6. Part 1 (Phase 1) - Exploratory: To evaluate preliminary evidence of pharmacodynamics effects 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.
7. Part 2 (Phase 2a): To characterize the PK of PBP1510 and gemcitabine administered as combination therapy, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
8. Part 2 (Phase 2a): To evaluate additional clinical benefits 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.
9. Part 2 (Phase 2a): To evaluate the immunogenicity 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.
10. Part 2 (Phase 2a) - Exploratory: To explore the relationship between pre-treatment PAUF expression levels 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.
11. Part 2 (Phase 2a) - Exploratory: To characterize the pharmacodynamic effects 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.

Conditions and MedDRA coding

Advanced and/or metastatic pancreatic adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Adults ≥ 18 years of age (or the legal age of majority in the country of recruitment) at the time consent is obtained.
2. 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.
3. 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.
4. Patients must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
5. 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.
6. 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.
7. Patient should understand, voluntarily sign, and date the written consent form prior to any protocol-specific procedures.
8. Performance Status score less than or equal to 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
9. Have histological or cytological evidence of a diagnosis of pancreatic adenocarcinoma that is advanced and/or metastatic.
10. Have a life expectancy of ≥ 3 months.
11. At least one measurable lesion as per RECIST v1.1.
12. 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 16

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.
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 currently has active hepatitis B, hepatitis C, or syphilis.
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 2 years, except for adequately treated and cured basal or squamous cell skin cancer.
9. Patients who are enrolled in any other therapeutic clinical trial, unless they have confirmed disease progression in the trial and area in follow-up.
10. 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.
11. 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.
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 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.
2. 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.
3. 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.

Secondary endpoints 11

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prestige Biopharma Ltd

Sponsor organisation

Prestige Biopharma Ltd

Address

21 Biopolis Road, #04-24 28 Nucleos South Building Biopolis #04-24 28 Nucleos South Building Biopolis

City

Singapore

Postcode

138567

Country

Singapore

Scientific contact point

Organisation

Prestige Biopharma Ltd

Contact name

PAUF-I Clinical Trial Team

Public contact point

Organisation

Prestige Biopharma Ltd

Contact name

PAUF-I Clinical Trial Team

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications