XB2001 + Chemotherapy for Pancreatic Cancer

(1-BETTER Trial)

Not currently recruiting at 29 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, XB2001, combined with chemotherapy for individuals with advanced pancreatic cancer. The first part of the trial determines the safest dose of XB2001 with chemotherapy. In the second part, participants will receive either XB2001 with chemotherapy or a placebo with chemotherapy to assess XB2001's effectiveness. The trial seeks participants with pancreatic cancer that has spread or returned and who have experienced disease progression after specific treatments. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this potential new therapy.

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.

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

Previous studies have shown that combining XB2001 with chemotherapy improved safety for patients with advanced pancreatic cancer. The treatment was generally well tolerated, with no very severe side effects reported. Some patients experienced moderate side effects, such as low white blood cell counts and low platelet counts, which were the most common serious issues. Overall, the research suggests that adding XB2001 to traditional chemotherapy might offer a safer option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

XB2001 is unique because it offers a new approach to tackling pancreatic cancer by potentially enhancing the effectiveness of chemotherapy. Unlike standard treatments that primarily focus on directly attacking cancer cells, XB2001 could work by targeting specific pathways that help the cancer grow and survive, making the chemotherapy drugs more effective. This novel mechanism might improve treatment outcomes for patients who often have limited options. Researchers are excited about XB2001 as it may provide a more powerful combination therapy that could lead to better response rates and prolonged survival for those battling this challenging disease.

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

Research shows that XB2001, one of the treatments in this trial, may help treat advanced pancreatic cancer when combined with chemotherapy. Participants will receive either XB2001 or a placebo, both alongside ONIVYDE, 5-FU, and leucovorin. Studies suggest that XB2001 enhances treatment safety and might improve survival rates for patients who have previously received other treatments. XB2001 is a monoclonal antibody that targets and blocks a protein called IL-1α, which is involved in inflammation that aids tumor growth and spread. By blocking IL-1α, XB2001 may slow tumor growth and protect healthy tissues. Early results indicate it could be a promising new treatment for advanced pancreatic cancer. ^{1 2 3 4 5}

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]

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]

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]

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]

Citations

1. onclive.com onclive.com/view/addition-of-xb2001-to-chemo-improves-safety-in-advanced-pancreatic-cancer

Addition of XB2001 to Chemo Improves Safety ... - OncLive XB2001 plus chemotherapy improved safety and was tied to a trend toward improved overall survival in pretreated advanced pancreatic cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04825288

Study Details | NCT04825288 | XB2001 in Combination ... XB2001 is a True Human monoclonal antibody that blocks the biological activity of IL-1α with a high degree of affinity and specificity. IL-1⍺ is a key mediator ...

3. withpower.com withpower.com/trial/phase-2-pancreatic-neoplasms-4-2021-67613?lat=36.65114&lng=-97.3517

XB2001 + Chemotherapy for Pancreatic Cancer (1-BETTER Trial) Research shows that combining nab-paclitaxel with gemcitabine improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone.

4. investors.xbiotech.com investors.xbiotech.com/news-releases/news-release-details/xbiotech-announces-first-patient-enrolled-clinical-trial

XBiotech Announces First Patient Enrolled in Clinical Trial ... XB2001 blocks inflammation pathways turned on by tumors that help tumors vascularize, spread and cause collateral damage to healthy tissues. By ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04825288

XB2001 in Combination With ONIVYDE + 5-FU/LV ... GlobeNewswire 2024 - XBiotech Results from Randomized Double-Blinded Phase 1/2 Study Suggest Potential Breakthrough Treatment for Advanced Pancreatic Cancer.