BXCL701 + Pembrolizumab for Pancreatic Cancer

(EXPEL PANC Trial)

Not currently recruiting at 4 trial locations

Overseen By Princess Jones

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: FAP inhibitors, DPP inhibitors

Disqualifiers: Pregnancy, Breastfeeding, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment combination for pancreatic ductal adenocarcinoma, a type of pancreatic cancer. The focus is on whether the drugs BXCL701 (an experimental treatment) and pembrolizumab (an immunotherapy drug) can prevent the cancer from worsening over 18 weeks. The trial is open to individuals who have previously tried other treatments for metastatic pancreatic cancer without success. Participants should have a type of pancreatic cancer that has spread and be willing to undergo biopsies. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires a 'washout period' (time without taking certain medications) of at least 2 weeks for prior anti-tumor therapy before starting the study. It's best to discuss your specific medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that the combination of BXCL701 and pembrolizumab is likely to be safe for humans?

Researchers are exploring a combination of two drugs, BXCL701 and pembrolizumab, to treat certain cancers, including pancreatic cancer. In studies with these drugs, patients have experienced some expected side effects. These occur because the drugs help the immune system fight cancer. However, most patients tolerate the treatment well.

Pembrolizumab is already approved for other cancers, so its safety is well understood. BXCL701 is still under investigation, but no major safety concerns have emerged so far. Prospective trial participants should discuss any questions or concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for pancreatic cancer?

Researchers are excited about BXCL701 combined with Pembrolizumab for pancreatic cancer because it offers a unique approach compared to traditional treatments like chemotherapy and radiation. Most treatments for pancreatic cancer try to kill cancer cells directly, but BXCL701 works differently by modulating the immune system. It activates the body's natural killer cells, enhancing the immune response against the cancer. Pembrolizumab, an immune checkpoint inhibitor, further boosts this effect by preventing cancer cells from evading immune detection. This dual approach could potentially offer more effective and targeted treatment options for patients.

What evidence suggests that the combination of BXCL701 and pembrolizumab might be an effective treatment for pancreatic cancer?

Research has shown that using BXCL701 with pembrolizumab, the combination studied in this trial, may help treat pancreatic ductal adenocarcinoma. In one study, patients who received this combination lived for an average of 13.6 months, while those who only received a checkpoint inhibitor lived for an average of 7.6 months. BXCL701 boosts the immune system to attack the tumor, potentially enhancing treatment effectiveness. This combination could better manage advanced pancreatic cancer compared to other treatments. These findings suggest that this combined treatment might be a more effective option for managing this type of cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Benjamin Weinberg, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

Adults with metastatic pancreatic ductal adenocarcinoma who've had one prior treatment can join. They must be able to swallow pills, consent to biopsies, and have measurable disease. Women of childbearing age need a negative pregnancy test and agree to contraception. Exclusions include pregnant/breastfeeding women, other recent cancers except certain skin/cervical cancers, uncontrolled medical conditions or heart disease, active infections like HIV/hepatitis, autoimmune diseases needing systemic treatment in the past 2 years (except for some exceptions), and those on steroids/immunosuppressants.

Inclusion Criteria

My pancreatic cancer has spread and is mainly adenocarcinoma.

I can take care of myself and am up and about more than half of my waking hours.

Measurable disease by iRECIST v. 1.1 criteria on baseline imaging

Exclusion Criteria

Psychiatric illness or social situation that would limit compliance with study requirements

I haven't had cancer treatment in the last 2 weeks.

My CNS cancer meets specific eligibility criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BXCL701 and pembrolizumab to determine the 18-week progression-free survival rate

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BXCL701
• Pembrolizumab

Trial Overview The trial is testing BXCL701 combined with Pembrolizumab in patients who have already undergone one line of therapy for their cancer. It's an open-label study where all participants receive the same treatment without a comparison group. The main goal is to see if this combination helps patients avoid cancer progression for at least 18 weeks.

How Is the Trial Designed?

Group I: BXCL701 plus Pembrolizumab Experimental Treatment 2 Interventions

BXCL701 is already approved in United States for the following indications:

Approved in United States as BXCL701 for:

• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndrome (MDS)
• Small Cell Neuroendocrine Prostate Cancer (SCNC)
• Pancreatic Cancer
• Stage IIb to IV Melanoma
• Soft Tissue Sarcoma

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

BioXcel Therapeutics Inc

Industry Sponsor

Trials

20

Recruited

2,400+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase IIa study involving 59 patients with metastatic pancreatic ductal adenocarcinoma (PDAC), the CXCR4 antagonist BL-8040 combined with pembrolizumab showed a disease control rate of 34.5% in chemotherapy-resistant patients, with a median overall survival of 3.3 months, and 7.5 months for those receiving it as second-line therapy.

When BL-8040 was combined with pembrolizumab and chemotherapy, the treatment resulted in an objective response rate of 32% and a disease control rate of 77%, indicating that this combination may enhance the effectiveness of chemotherapy in PDAC and should be further investigated in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Bockorny, B., Semenisty, V., Macarulla, T., et al.[2021]

In a study of 41 pancreas cancer patients treated with pembrolizumab, the median overall survival was 7.2 months, which is considered favorable compared to the benchmark of over 4 months.

Patients with specific genetic markers (dMMR, MSI-H, TMB-H, or Lynch syndrome) had a significantly lower risk of death, indicating that these biomarkers may help identify patients who could benefit more from pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. Storandt, MH., Tran, N., Martin, N., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

The combination of galunisertib and durvalumab was found to be tolerable with no dose-limiting toxicities, and the recommended dose for further studies was established at 150 mg of galunisertib taken twice daily alongside durvalumab.

While the treatment showed a disease control rate of 25% among 32 patients, clinical activity was limited, suggesting that this combination may be more effective if used earlier in treatment or in patients selected based on specific biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer. Melisi, D., Oh, DY., Hollebecque, A., et al.[2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

The BTK inhibitor Tirabrutinib effectively reduces the differentiation of pro-tumorigenic CD1dhiCD5+ regulatory B cells in pancreatic ductal adenocarcinoma, which are known to promote tumor growth.

In mouse models of pancreatic cancer, Tirabrutinib treatment not only decreased the population of these regulatory B cells but also increased the presence of cytotoxic T cells, leading to reduced tumor cell proliferation and growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTK signaling drives CD1dhiCD5+ regulatory B-cell differentiation to promote pancreatic carcinogenesis. Das, S., Bar-Sagi, D.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1. ir.bioxceltherapeutics.com ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-overall-survival-results

Press Release Median overall survival of 13.6 months with BXCL701 + KEYTRUDA® (pembrolizumab), compared to 7.6 months with checkpoint inhibitor monotherapy (CPI) in late- ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-07433

BXCL701 and Pembrolizumab for the Treatment of Patients ... Giving BXCL701 in combination with pembrolizumab may work better in controlling disease growth in patients with metastatic pancreatic ductal cancer than giving ...

3. ir.bioxceltherapeutics.com ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announces-completion-patient-enrollment-0

Press Release The trial is evaluating BXCL701, an investigational, oral innate immune activator designed to inflame the tumor microenvironment and thereby augment the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04171219

Talabostat and Pembrolizumab for the Treatment of ... This phase II trial studies the side effects of talabostat and pembrolizumab and to see how well they work for the treatment of solid cancers that have spread ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7915918/

Targeting and Reprograming Cancer-Associated Fibroblasts ... This review article summarizes recent preclinical and clinical investigations addressing pancreatic cancer therapy through targeting specific subtypes of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39853679/

A phase 2 basket study of talabostat, a small-molecule ... This study of the combination of talabostat and pembrolizumab in patients with advanced solid tumors demonstrated predictable adverse events ...