XB2001 + Chemotherapy for Pancreatic Cancer

(1-BETTER Trial)

Recruiting at 28 trial locations

Overseen By Norma Gonzalez

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: XBiotech, Inc.

Must not be taking: CYP3A4 inducers, UGT1A1 inhibitors

Disqualifiers: Brain metastases, Heart failure, others

Compensation: Varies

Number of Visits: 16

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial will include 2 portions (phase 1 and phase 2). The first portion will be a Phase I, open label, dose escalation study to establish the maximum tolerated dose (MTD) of XB2001 as measured by Dose-Limiting Toxicity (DLT), in combination with ONIVYDE + LV + 5-FU chemotherapy regimen in patients with advanced pancreatic cancer and to determine the recommended dose for the subsequent Phase 2 study. The phase 2 portion will be implemented with the maximum established tolerated dose (MTD) of XB2001. The target enrollment in the phase 2 portion is 60 patients which will be randomized on a 1:1 basis to XB2001 plus ONIVYDE + LV + 5-FU (Arm 1) or placebo plus ONIVYDE + LV + 5-FU (Arm 2).

Will I have to stop taking my current medications?

The trial requires that you stop using strong CYP3A4 inducers or inhibitors and UGT1A1 inhibitors at least 14 days before starting the trial. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What safety data exists for XB2001 + chemotherapy in humans?

The safety of nab-paclitaxel plus gemcitabine, which is part of the chemotherapy regimen, has been evaluated in several studies. It showed an acceptable safety profile in patients with advanced solid tumors, including pancreatic cancer, and was generally well-tolerated in real-life practice. ^{1 2 3 4 5}

What makes the drug XB2001 unique for treating pancreatic cancer?

The drug XB2001 is unique for treating pancreatic cancer because it is being tested in combination with chemotherapy, potentially offering a new approach compared to existing treatments like FOLFIRINOX or gemcitabine with nab-paclitaxel, which are standard regimens. This combination could provide a novel mechanism or improved effectiveness, although specific details about XB2001's action or benefits are not provided in the available research. ^{6 7 8 9 10}

What data supports the effectiveness of the drug XB2001 for pancreatic cancer?

Research shows that combining nab-paclitaxel with gemcitabine improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This suggests that combination therapies, like XB2001 with chemotherapy, might also be effective. ^{3 5 11 12 13}

Who Is on the Research Team?

David J Park

Principal Investigator

Providence St. Joseph Heritage

Are You a Good Fit for This Trial?

This trial is for adults with advanced pancreatic cancer who've had disease progression after one prior gemcitabine-based therapy or a FOLFIRINOX and gemcitabine combo. They must have at least one measurable tumor, be relatively fit (ECOG 0-1 or KPS ≥70), and their major organs need to function well. Exclusions include recent severe heart issues, brain metastases, certain GI disorders, and use of strong CYP3A4/UGT1A1 drugs recently.

Inclusion Criteria

My cancer progressed after treatment with gemcitabine or FOLFIRINOX and gemcitabine.

You have at least one spot that can be measured according to specific guidelines for evaluating tumors.

My pancreatic cancer is confirmed and cannot be removed by surgery.

Exclusion Criteria

I have not had a severe blood clot in my arteries in the last 6 months.

I haven't taken strong CYP3A4 or UGT1A1 inhibitors in the last 14 days.

My cancer has spread to my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Phase I Treatment

Open label, dose escalation study to establish the maximum tolerated dose (MTD) of XB2001 in combination with ONIVYDE + LV + 5-FU

2 weeks

1 visit (in-person)

Phase II Treatment

Randomized, double-blind, placebo-controlled study with XB2001 or placebo in combination with ONIVYDE + LV + 5-FU

24 weeks

12 visits (in-person, every 2 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Open-label Extension

Participants may continue treatment with XB2001 as long as they are benefitting clinically and have no unacceptable toxicities

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• XB2001

Trial Overview The study tests XB2001 combined with ONIVYDE + LV + 5-FU chemotherapy in two phases: Phase 1 finds the safest high dose (MTD) without serious side effects; Phase 2 uses this MTD in half the patients while the other half receive a placebo plus standard chemo. Patients are randomly assigned to these groups.

How Is the Trial Designed?

Group I: Arm 1 Active Control 1 Intervention

XB2001 + ONIVYDE + 5-FU + LV combination therapy administered for 12 cycles of treatment • Arm 1 Treatment Cycle: Patients randomized to this arm will receive the following treatments every 2 weeks: XB2001 MTD as an intravenous infusion over up to 60 minutes, followed by ONIVYDE 70 mg/m2 intravenously over 90 minutes, followed by leucovorin l + d racemic 400 mg/m2 intravenously over 30 minutes, followed by 5-Fluorouracil 2400mg/m2 intravenously over 46 hours. Therapy will be administered every 2 weeks (2 weeks = 1 cycle).

Group II: Arm 2 Placebo Group 1 Intervention

Placebo + ONIVYDE + 5-FU + LV combination therapy administered for 12 cycles of treatment • Arm 2 Treatment Cycle: Patients randomized to this arm will receive the following treatments every 2 weeks: Placebo as an intravenous infusion over up to 60 minutes, followed by ONIVYDE 70 mg/m2 intravenously over 90 minutes, followed by leucovorin l + d racemic 400 mg/m2 intravenously over 30 minutes, followed by 5-fluorouracil 2400 mg/m2 intravenously over 46 hours. Therapy will be administered every 2 weeks (2 weeks = 1 cycle).

Who Is Running the Clinical Trial?

XBiotech, Inc.

Lead Sponsor

Trials

8

Recruited

740+

Published Research Related to This Trial

In a study of 41 patients with advanced pancreatic adenocarcinoma, the combination of Nab-paclitaxel and gemcitabine showed an overall response rate of 36.6%, with a median progression-free survival of 6.7 months and median overall survival of 10 months, indicating its efficacy as a first-line treatment.

The treatment was well tolerated, with no grade 4 toxicities reported; the most common grade 3 toxicities included neutropenia and thrombocytopenia, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. De Vita, F., Ventriglia, J., Febbraro, A., et al.[2023]

The introduction of nab-paclitaxel combined with gemcitabine has significantly improved survival rates for patients with advanced pancreatic cancer, as demonstrated in the MPACT study from 2013.

Prior to 2011, treatment options for pancreatic cancer were limited, primarily relying on gemcitabine, but the Phase III results of FOLFIRINOX and subsequent studies have expanded the therapeutic options available for oncologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel and gemcitabine for the treatment of patients with metastatic pancreatic cancer. Borazanci, E., Von Hoff, DD.[2022]

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 study of 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., et al.[2022]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel and gemcitabine for the treatment of patients with metastatic pancreatic cancer. [2022]

4. China pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

7. Singapore pubmed.ncbi.nlm.nih.gov

Low-dose nab-paclitaxel-based combination chemotherapy in heavily pretreated pancreatic cancer patients. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

A Phase I/II Open-Label Multicenter Single-Arm Study of FABLOx (Metronomic 5-Fluorouracil Plus nab-Paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin) in Patients with Metastatic Pancreatic Cancer. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Combination of gemcitabine, nab-paclitaxel, and S-1(GAS) as the first-line treatment for patients with locally advanced or advanced pancreatic ductal adenocarcinoma: study protocol for an open-label, single-arm phase I study. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Intensified Neoadjuvant Chemotherapy with Nab-Paclitaxel plus Gemcitabine Followed by FOLFIRINOX in a Patient with Locally Advanced Unresectable Pancreatic Cancer. [2020]

12. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]

13. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of Combination Therapy with Nab-paclitaxel Plus Gemcitabine in Patients with Recurrent Pancreatic Cancer. [2022]