BXCL701 + Pembrolizumab for Pancreatic Cancer

(EXPEL PANC Trial)

Recruiting at 2 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

43 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination BXCL701 and Pembrolizumab for pancreatic cancer?

Research shows that combining pembrolizumab with other treatments can help some patients with pancreatic cancer, as seen in a study where a similar drug combination improved disease control and survival in certain patients. This suggests that pembrolizumab might work better when used with other drugs, like BXCL701, for treating pancreatic cancer. ^{1 2 3 4 5}

Is the combination of BXCL701 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, nausea, and immune-related issues such as thyroid problems and rare cases of type 1 diabetes. While specific safety data for the combination with BXCL701 is not provided, pembrolizumab's safety profile in other conditions suggests it is generally well-tolerated with some risks. ^{1 6 7 8 9}

What makes the drug combination of BXCL701 and Pembrolizumab unique for pancreatic cancer?

The combination of BXCL701 and Pembrolizumab is unique because it targets multiple pathways in the immune system to enhance the body's ability to fight pancreatic cancer, which is typically resistant to single-agent PD-1 inhibitors like Pembrolizumab alone. ^{1 2 4 5 6}

What is the purpose of this trial?

This trial is testing a combination of two drugs, BXCL701 and pembrolizumab, in patients with advanced pancreatic cancer. These patients have already tried other treatments without success. The drugs work together to help the immune system better identify and attack cancer cells. Pembrolizumab has shown effectiveness in patients with various cancers, including pancreatic cancer.

Research Team

Benjamin Weinberg, MD

Principal Investigator

Georgetown University

Eligibility Criteria

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

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

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

My CNS cancer meets specific eligibility criteria.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. [2021]

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

BTK signaling drives CD1dhiCD5+ regulatory B-cell differentiation to promote pancreatic carcinogenesis. [2020]

4. Germany 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. [2023]

5. England 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. [2021]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]