BXCL701 + Pembrolizumab for Prostate Cancer

No longer recruiting at 18 trial locations

Overseen By Michel Duval, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: BioXcel Therapeutics Inc

Must be taking: LHRH analogs

Must not be taking: DPP4 inhibitors

Disqualifiers: Active malignancy, Cardiovascular disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for prostate cancer that has spread and resists hormone therapy. It examines the safety and effectiveness of combining two drugs, BXCL701 (an experimental treatment) and pembrolizumab (an immunotherapy drug), to evaluate their performance both individually and together. The trial is open to patients whose prostate cancer continues to grow despite previous treatments. Participants should have tried at least one other therapy for advanced prostate cancer that was unsuccessful. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering 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 if you need to stop taking your current medications. However, it mentions that you cannot have received certain treatments like external-beam radiation or investigational systemic anticancer agents within 14 days before starting the study. It's best to discuss your current medications with the study team to ensure they don't conflict with the trial requirements.

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

Research has shown that the investigational treatment BXCL701 is under study for its safety and effectiveness in treating prostate cancer. BXCL701, a pill that blocks certain proteins, might help the immune system fight cancer. Previous studies suggest it can be well-tolerated, but more research is needed to confirm its safety.

Pembrolizumab, also part of the study, has already received FDA approval for other cancers. It has proven safe and effective in patients with advanced prostate cancer. Past studies indicate that pembrolizumab is generally safe, though some patients may experience side effects like tiredness or a rash.

Researchers are testing both treatments together to determine if they work better as a pair. Since this trial is in the early stages, it focuses on how well patients can tolerate these drugs. Safety will be closely monitored throughout the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BXCL701 combined with Pembrolizumab for prostate cancer because it introduces a unique approach to treatment. Unlike traditional treatments that often involve hormone therapy or chemotherapy, BXCL701 is an oral immunomodulator designed to enhance the body's immune response against cancer cells. Pembrolizumab, a well-known immune checkpoint inhibitor, works by unleashing the immune system to attack tumors. Together, they offer a promising new mechanism that may lead to more effective results by targeting the disease on multiple fronts. This combination has the potential to improve outcomes for patients with advanced prostate cancer by leveraging the body's natural defenses in a novel way.

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

Research has shown that BXCL701, one of the treatments in this trial, holds promise for treating prostate cancer when used alone. In past studies, patients with hard-to-treat types lived for about 9.5 months on average, even though the main goal of the study was not fully achieved. However, some patients responded very well to the treatment.

This trial also examines BXCL701 in combination with pembrolizumab. Early results suggest this combination might have stronger effects against tumors. It could help the immune system fight cancer cells more effectively. Studies have examined its effects on solid cancers, indicating it might also work for prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Amir Hafeez, MD

Principal Investigator

Bioxcel Therapeutics

Vincent O'Neill, MD

Principal Investigator

Bioxcel Therapeutics

Are You a Good Fit for This Trial?

This trial is for men with advanced prostate cancer that's resistant to hormone therapy and has spread. Participants must have either small cell neuroendocrine cancer or adenocarcinoma, be willing to undergo a biopsy, and have received prior chemotherapy. They should not have other active cancers or certain heart conditions, and can't have had recent treatments that could interfere with the study.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

My side effects from cancer treatment are mild, except for possible nerve pain or hair loss.

My testosterone levels are below 50 ng/dL, except if I have a specific type of prostate cancer.

Exclusion Criteria

I have had dizziness or fainting when standing up in the last 3 months.

I have an autoimmune disease or severe lung inflammation treated in the last 2 years.

My cancer has spread to my brain or its coverings and is getting worse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b

Safety and tolerability of BXCL701 in combination with PEMBRO are assessed, with dose escalation based on dose-limiting toxicities

21-day cycles

Multiple visits for dose escalation and monitoring

Phase 2a

Patients receive BXCL701 in combination with PEMBRO, grouped by phenotype into Cohort A or B

21-day cycles

Regular visits for treatment and monitoring

Phase 2b

Randomized treatment based on histologic subtype showing preliminary efficacy in Phase 2a, with BXCL701 and PEMBRO combination or BXCL701 monotherapy

21-day cycles

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• BXCL701
• Pembrolizumab

Trial Overview

The trial is testing BXCL701 alone and combined with Pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). It aims to find the best dose, check how well it works, and monitor safety. The study includes multiple phases where different patient groups are treated based on their type of cancer.

How Is the Trial Designed?

Group I: Phase 2b monotherapy Experimental Treatment 1 Intervention

Upon completion of the Phase 2a and achievement of the protocol required composite responses for a given histologic subtype, the Phase 2b enrollment will begin for that subtype. Eligible patients will be randomized to receive: * Monotherapy BXCL701 on Days 1 to 14 of a 21-day cycle. Upon radiographic disease progression with monotherapy, crossover to combination treatment is allowed.

Group II: Phase 2b combination Experimental Treatment 1 Intervention

Upon completion of the Phase 2a and achievement of the protocol required composite responses for a given histologic subtype, the Phase 2b enrollment will begin for that subtype. Eligible patients will be randomized to receive: • Combination therapy of BXCL701 on Days 1 to 14 of a 21-day cycle plus PEMBRO 200 mg administered IV on Day 1 of every 21 days.

Group III: Phase 2a Experimental Treatment 1 Intervention

After assessment of the safety and confirmation of the BXCL701/+PEMBRO dose schedule to be used in the subsequent stage, the Phase 2a will begin. Eligible patients will receive BXCL701 QD on Days 1 to 14 of a 21-day cycle plus PEMBRO 200 mg administered IV on Day 1 every 21 days.

Group IV: Phase 1b Experimental Treatment 1 Intervention

Patients will be observed for dose-limiting toxicity (DLT) during Cycle 1. 3 patients will be treated initially with 0.4 mg BXCL701 plus PEMBRO: If there are no DLTs, the dose of BXCL701 will be escalated to 0.6 mg in the next cohort. If ≥1/3 of patients has a DLT in Cycle 1, either 3 patients (if 1 experience a DLT) or 6 to 9 patients (if 2 or 3 experiences a DLT) will be added at the 0.4 mg dose. At the 0.4mg dose: If \<1/3 of the patients experience a DLT, consideration will be given to dose to 0.6 mg BXCL701 plus PEMBRO. If 1/3 of the patients experience a DLT, the Phase 2a can commence. If \>1/3 of the patients experience a DLT, a discussion will be held as to how to proceed. Following 0.6 mg dose. If there are no DLTs, the Phase 2a can commence. If ≥1/3 patients have a DLT in Cycle 1, after a discussion, 6 to 9 patients will be added at the 0.6 mg dose. For this cohort of 6 to 9 patients: If \</=1/3 of the patients experience a DLT, the Phase 2a can commence

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?

BioXcel Therapeutics Inc

Lead Sponsor

Trials

20

Recruited

2,400+

Published Research Related to This Trial

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 study of 206 men with previously untreated metastatic castration-resistant prostate cancer (mCRPC) harboring PD-L1 staining, the combination of pembrolizumab (PEM) and enzalutamide (ENZ) significantly improved overall survival (25.1 months) and progression-free survival (6.1 months) compared to PEM alone (18.3 months and 4.9 months, respectively).

While the combination treatment had a higher rate of adverse events (72% for PE vs. 45.3% for PA), these side effects, including fatigue and musculoskeletal issues, were generally manageable, indicating a favorable safety profile for the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or without enzalutamide in selected populations of men with previously untreated metastatic castration-resistant prostate cancer harbouring programmed cell death ligand-1 staining: a retrospective study. Lin, H., Liu, Q., Zeng, X., 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]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

The KEYNOTE-641 study is a Phase III clinical trial designed to evaluate the safety and efficacy of combining the PD-1 inhibitor pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC).

This trial aims to determine if the combination therapy can improve outcomes compared to enzalutamide alone, addressing the need for more effective treatments in a patient population with a median survival of about 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. Graff, JN., Liang, LW., Kim, J., et al.[2021]

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]

In a study of 54 men with advanced prostate cancer treated with pembrolizumab, about 55% experienced stabilization or a decline in PSA levels, indicating modest efficacy of the treatment.

Men who started pembrolizumab with lower PSA levels and fewer bone metastases had a higher likelihood of responding to the treatment, suggesting that earlier intervention may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Experience With Pembrolizumab in Recurrent or Advanced Prostate Cancer. Higa, J., Wilenius, K., Savino, S., et al.[2021]

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