PBP1510 + Gemcitabine for Pancreatic Cancer

Recruiting at 3 trial locations

Overseen By Mei Li Lim

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Prestige Biopharma Limited

Must be taking: Gemcitabine

Disqualifiers: Brain metastases, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with advanced or spreading pancreatic cancer. Researchers aim to evaluate how the drug PBP1510 (Ulenistamab) performs both alone and in combination with gemcitabine (Gemzar). The goal is to determine the optimal dose and assess the effectiveness of these treatments against cancer. Individuals with pancreatic cancer unresponsive to standard chemotherapy may be suitable candidates for this study. As a Phase 1 trial, this research seeks to understand how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the study team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that PBP1510 is safe for patients with advanced cancer when used alone at doses up to 6 mg/kg, allowing patients to take this treatment without severe side effects at these doses.

When combined with gemcitabine, studies indicate that PBP1510 is safe up to 3 mg/kg. Patients did not experience major issues with this combination, suggesting safety at these levels.

These findings come from early trials focused on safety. It is important to note that gemcitabine is a well-known drug often used in cancer treatments, which adds reassurance about its safety. Overall, the evidence suggests that both treatments are reasonably safe for use in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PBP1510 in combination with gemcitabine for pancreatic cancer because it represents a novel approach compared to existing treatments. Unlike standard chemotherapy options like FOLFIRINOX and gemcitabine with nab-paclitaxel, PBP1510 specifically targets a protein called PLA2G1B, which is involved in cancer cell growth. This targeted mechanism could enhance the effectiveness of traditional chemotherapy and offer a more personalized treatment strategy. Additionally, using PBP1510 at different dosages, both alone and with gemcitabine, provides flexibility in tailoring treatment to patient needs, potentially reducing side effects while maximizing efficacy.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research shows that PBP1510, a new antibody treatment, targets a protein called PAUF, often found in people with pancreatic cancer. In animal studies, PBP1510 reduced cancer growth. Early human studies suggest that this treatment is safe at doses up to 6 mg/kg. In this trial, some participants will receive PBP1510 as monotherapy at various doses, while others will receive it with gemcitabine, a common chemotherapy drug. When combined with gemcitabine, patients with advanced pancreatic cancer tolerated PBP1510 at doses up to 3 mg/kg. Gemcitabine is known to improve survival when used with other drugs. These findings give hope that PBP1510, alone or with gemcitabine, could effectively treat pancreatic cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Peggy Feyaerts

Principal Investigator

Prestige Biopharma Limited

Are You a Good Fit for This Trial?

Adults over 18 with advanced/metastatic pancreatic cancer, who have had at least one line of standard chemotherapy, can join this trial. They must be in relatively good health (ECOG score ≤1), expect to live more than 3 months, and have no other major illnesses or recent surgeries that could affect the study. Women must not be pregnant and agree to use effective contraception.

Inclusion Criteria

You have at least one specific spot that can be measured according to a certain set of rules.

Patients enrolling into Part 1 (Phase 1) of the study must also meet the following inclusion criteria:

Criterion: Your blood counts, liver function, kidney function, and heart function need to be within certain normal ranges for you to participate in the trial.

Exclusion Criteria

Patients who are not eligible to participate in this study, as judged by Investigators.

I have heart problems that are not well-controlled.

You are allergic to any ingredients in the PBP1510 drug, or have had a bad reaction to similar medications made from Chinese hamster ovary cells or other genetically engineered antibodies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation (Phase 1)

PBP1510 is administered as monotherapy or in combination with gemcitabine to determine the recommended Phase 2a dose (RP2D).

4 cycles of 28 days each

Multiple visits per cycle (C1D1, C1D8, C1D15, etc.)

Dose-Expansion (Phase 2a)

Patients receive the RP2D of PBP1510 in combination with gemcitabine to assess efficacy and safety.

4 cycles of 28 days each

Multiple visits per cycle (C1D1, C1D8, C1D15, etc.)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

90 days after last dose

Safety Follow Up visit

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• PBP1510

Trial Overview The trial is testing PBP1510 alone and combined with gemcitabine in patients with pancreatic cancer. It's a two-part study: first part tests different doses of PBP1510 alone and then with gemcitabine; second part expands the dose found to be safe in combination with gemcitabine.

How Is the Trial Designed?

Group I: Cohort 5M Experimental Treatment 1 Intervention

15 mg/kg of PBP1510 as monotherapy will be administered

Group II: Cohort 5C Experimental Treatment 2 Interventions

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

Group III: Cohort 4M Experimental Treatment 1 Intervention

10 mg/kg of PBP1510 as monotherapy will be administered

Group IV: Cohort 4C Experimental Treatment 2 Interventions

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

Group V: Cohort 3M Experimental Treatment 1 Intervention

6 mg/kg of PBP1510 as monotherapy will be administered

Group VI: Cohort 3C Experimental Treatment 2 Interventions

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

Group VII: Cohort 2M Experimental Treatment 1 Intervention

3 mg/kg of PBP1510 as monotherapy will be administered

Group VIII: Cohort 2C Experimental Treatment 2 Interventions

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

Group IX: Cohort 1M Experimental Treatment 1 Intervention

1 mg/kg of PBP1510 as monotherapy will be administered

Group X: Cohort 1C Experimental Treatment 2 Interventions

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

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Prestige Biopharma Limited

Lead Sponsor

Trials

6

Recruited

1,800+

Published Research Related to This Trial

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

In a phase III study involving 360 patients with advanced pancreatic cancer, the combination of irinotecan and gemcitabine (IRINOGEM) significantly improved tumor response rates (16.1%) compared to gemcitabine alone (4.4%), indicating enhanced efficacy in shrinking tumors.

Despite the improved tumor response, IRINOGEM did not lead to a significant increase in overall survival, with median survival times being similar (6.3 months for IRINOGEM vs. 6.6 months for gemcitabine), and the treatment was associated with a higher incidence of grade 3 diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. Rocha Lima, CM., Green, MR., Rotche, R., et al.[2022]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[2022]

The addition of the EGFR inhibitor erlotinib to gemcitabine chemotherapy in pancreatic cancer patients resulted in a modest but significant increase in survival, highlighting the potential of targeting EGFR in treatment.

A Phase II trial combining gemcitabine with the anti-EGFR antibody cetuximab achieved a notable 1-year survival rate of 32%, suggesting that targeted therapies may improve outcomes in pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Her signaling in pancreatic cancer. Burtness, B.[2022]

In a study of 670 Veterans with advanced pancreatic cancer, the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed similar overall survival rates compared to FOLFIRINOX, indicating that Gem/NabP is noninferior to FOLFIRINOX for this patient population.

The study utilized a novel tumor growth formula based on CA19-9 biomarker data, suggesting that this approach could be valuable for monitoring treatment responses and predicting outcomes in pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus nab-paclitaxel versus FOLFIRINOX for unresected pancreatic cancer: Comparative effectiveness and evaluation of tumor growth in Veterans. Sigel, K., Zhou, M., Park, YA., et al.[2023]

In a phase III trial involving 319 patients with advanced pancreatic cancer, the combination of gemcitabine and capecitabine (GemCap) did not significantly improve overall survival compared to gemcitabine alone, with median survival times of 8.4 months for GemCap and 7.2 months for Gem.

However, in patients with a good performance status (Karnofsky score of 90-100), GemCap showed a significant improvement in median overall survival (10.1 months vs. 7.4 months for Gem), suggesting it may be a beneficial alternative for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. Herrmann, R., Bodoky, G., Ruhstaller, T., et al.[2022]

In a phase II study involving 44 patients with advanced pancreatic cancer, the combination of gemcitabine, capecitabine, erlotinib, and bevacizumab showed a confirmed radiological response rate of 23%, indicating potential efficacy in this difficult-to-treat cancer.

The treatment regimen was found to be feasible with manageable side effects, including neutropenia and lethargy, and resulted in a median overall survival of 12.6 months for all patients, and 10.1 months for those with metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of a chemotherapy doublet (gemcitabine and capecitabine) with a biological doublet (bevacizumab and erlotinib) in patients with advanced pancreatic adenocarcinoma. The results of a phase I/II study. Watkins, DJ., Starling, N., Cunningham, D., et al.[2022]

Pak1 is identified as a key signaling kinase that contributes to gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC) by modulating processes like epithelial-mesenchymal transition and activating pancreatic stellate cells, as demonstrated through in vitro and in vivo models.

Inhibiting Pak1 enhances the effectiveness of gemcitabine, leading to increased cytotoxicity and tumor regression in mouse models, suggesting that Pak1 inhibitors could serve as valuable adjuncts to existing chemotherapy for PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P21-activated kinase 1 (Pak1) signaling influences therapeutic outcome in pancreatic cancer. Jagadeeshan, S., Subramanian, A., Tentu, S., et al.[2022]

The combination of gemcitabine, capecitabine, bevacizumab, and erlotinib showed promising efficacy in treating advanced pancreatic cancer, with 10 partial responses observed among 20 patients and median overall survival of 12.5 months.

The maximum-tolerated dose of capecitabine was determined to be 1,660 mg/m², with a recommended dose of 1,440 mg/m² for further studies, while the treatment was generally well-tolerated with manageable side effects like diarrhea and skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. Starling, N., Watkins, D., Cunningham, D., et al.[2022]

In a phase II trial involving 17 patients with advanced pancreatic cancer, the combination of sorafenib and gemcitabine showed no objective responses, with only 18% of patients achieving stable disease.

The treatment resulted in a median overall survival of 4.0 months and was associated with significant toxicities, including thrombosis in 18% of patients, indicating that this combination is not effective for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Kindler, HL., Wroblewski, K., Wallace, JA., et al.[2022]

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16363

First-in-human phase 1/2a study of PBP1510 (anti-PAUF ... PBP1510 demonstrate acceptable tolerability at up to 3 mg/kg in combination with gemcitabine in metastatic pancreatic adenocarcinoma patients who had failed ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05141149

Study Details | NCT05141149 | First in Human Phase1/2a ... PART 1 (PHASE 1) Exploratory Endpoint: Preliminary evidence of clinical outcomes as assessed by objective response rate (ORR) after treatment with PBP1510 ...

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT061/761349/Abstract-CT061-Preliminary-safety-results-from-the

Preliminary safety results from the first-in-human phase 1/2a ... Interim safety data from dose-escalation of the first-in-class PBP1510 demonstrates acceptable tolerability up to 6 mg/kg in advanced/metastatic ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00074-6/fulltext

In vivo efficacy and safety of PBP1510, a first in class ... Superior anti-tumour efficacy of PBP1510 treatment, compared to IgG control, was observed in all the three mouse models, particularly in PAUF-positive cancer ...

5. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-pbp1510-in-metastatic-pancreatic-adenocarcinoma

FDA Grants Fast Track Designation to PBP1510 ... - OncLive PBP1510 targets the tumor-specific protein PDAC upregulated factor (PAUF), which is overexpressed in most patients with pancreatic cancer. PAUF ...