Trimodality Therapy for Prostate Cancer

(TALON Trial)

Overseen By Daniel George, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: PD-1 inhibitors, PD-L1 inhibitors

Disqualifiers: Metastasis, Prior pelvic radiation, Autoimmune, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 7 weeks for Arm A, 3 weeks for Arm B

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating intermediate or high-risk prostate cancer. Researchers aim to determine if combining pembrolizumab (KEYTRUDA, an immunotherapy that aids the immune system in fighting cancer) with low-dose radiation before prostate surgery is safe and effective. The study compares this combination to using only radiation before surgery. This trial suits individuals diagnosed with intermediate or high-risk prostate cancer who plan to undergo surgery. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain cancer treatments or investigational drugs. It's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab, one of the treatments in the trial, is generally well-tolerated. Past studies found pembrolizumab to be safe for patients with advanced prostate cancer. Common side effects included tiredness and skin rash, which were usually manageable, while serious side effects were less common.

Low-dose prostate radiation is also considered safe, with manageable side effects. This type of radiation uses a lower dose to minimize harm to nearby tissues while effectively targeting cancer cells.

In summary, both treatments in this trial have demonstrated relative safety in other studies. Participants might experience side effects, but these are often mild and controllable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine innovative approaches. Unlike traditional treatments that often focus solely on surgery or radiation, this approach integrates pembrolizumab, an immunotherapy drug, which helps the immune system attack cancer cells more effectively. Additionally, the use of stereotactic body radiation therapy (SBRT) provides a highly targeted radiation dose, potentially minimizing damage to surrounding healthy tissue. This combination could enhance the effectiveness of prostate cancer treatment and reduce side effects, offering hope for better patient outcomes.

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

Research has shown that pembrolizumab may be helpful in treating prostate cancer, particularly in advanced stages. One study found that patients with metastatic prostate cancer experienced improvements in cancer markers and imaging results after receiving pembrolizumab. Another study discovered that patients whose prostate cancer did not respond to other treatments experienced a rapid decrease in disease markers after taking pembrolizumab. Additionally, when combined with other treatments, pembrolizumab showed positive results in combating prostate cancer. These findings suggest that pembrolizumab might enhance the immune system's ability to fight cancer.

In this trial, participants in Arm A will receive pembrolizumab along with low-dose prostate radiation and prostatectomy. Low-dose prostate radiation is believed to alter the appearance of tumor cells, potentially making them easier for the immune system to attack. This method might help immune cells better recognize and target cancer cells. Participants in Arm B will receive low-dose prostate radiation and prostatectomy without pembrolizumab. While limited data exists on using low-dose radiation alone for prostate cancer, combining it with pembrolizumab aims to leverage the strengths of both treatments to combat the disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Daniel George, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Men aged 18+ with intermediate/high-risk prostate cancer who can sign consent, have adequate organ function, and meet specific risk criteria (e.g., Gleason score, PSA levels) as per NCCN guidelines. Excluded are those with metastasis, prior pelvic treatments like radiation or cryotherapy, recent investigational drug use, active autoimmune diseases requiring systemic treatment within the past 2 years, chronic steroid/immunosuppressive drug use (with some exceptions), uncontrolled illnesses that could affect study compliance or safety.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

I am willing and able to follow the study's treatment plan and attend all visits.

My organs and bone marrow are functioning well.

Exclusion Criteria

I have had or currently have lung inflammation treated with steroids.

My cancer has spread to my bones, brain, organs, or soft tissues.

I have had radiation, cryotherapy, or HIFU treatments in the pelvic area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and low dose prostate radiation or low dose prostate radiation alone prior to prostatectomy

7 weeks for Arm A, 3 weeks for Arm B

Prostatectomy

Participants undergo prostatectomy as part of the treatment regimen

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PSA recurrence and prostate cancer recurrence

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Radical Prostatectomy
• Short-term androgen deprivation therapy
• Stereotactic body radiation therapy

Trial Overview The TALON trial is testing a 'trimodal therapy' for prostate cancer involving pembrolizumab (an immunotherapy drug), SBRT to the prostate gland, and short-term ADT followed by radical surgery to remove the prostate. The goal is to see if this combination delays the rise of PSA compared to historical data over a follow-up period of two years.

How Is the Trial Designed?

Group I: Arm B: Low dose prostate radiation and prostatectomy Experimental Treatment 2 Interventions

Participants in Arm B will receive: * Low dose prostate radiation of one dose of 2 Gy to the prostate and seminal vesicles * Prostatectomy as part of the routine care for their cancer

Group II: Arm A: pembrolizumab, low dose prostate radiation and prostatectomy Experimental Treatment 3 Interventions

Participants in Arm A will receive: * Pembrolizumab 400 mg intravenously every 6 weeks for 9 cycles. * Low dose prostate radiation of one dose of 2 Gy to the prostate and seminal vesicles * Prostatectomy as part of the routine care for their cancer

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Bridget Koontz

Lead Sponsor

Trials

1

Recruited

30+

Daniel George, MD

Lead Sponsor

Trials

8

Recruited

250+

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 II trial involving men with metastatic castration-resistant prostate cancer (mCRPC) who were progressing on enzalutamide, the anti-PD-1 antibody pembrolizumab showed unexpected antitumor activity, with three out of ten patients achieving significant reductions in prostate-specific antigen (PSA) levels.

The presence of immune cell infiltrates and PD-L1 expression in tumor biopsies from responders suggests that certain biological markers may predict the effectiveness of PD-1 inhibitors in prostate cancer, warranting further investigation into this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Graff, JN., Alumkal, JJ., Drake, CG., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

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 (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 (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

A 58-year-old patient with metastatic castration-resistant prostate cancer and microsatellite instability-high showed significant clinical improvement after treatment with pembrolizumab, including decreased prostate-specific antigen levels and reduced lymph node size.

This case suggests that pembrolizumab could be an effective treatment option for patients with microsatellite instability-high in castration-resistant prostate cancer, despite its rarity, marking a potential new avenue for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for a patient with metastatic castration-resistant prostate cancer with microsatellite instability-high. Fujiwara, M., Komai, Y., Yuasa, T., et al.[2022]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1558767325000849

Clinical Outcomes of Patients With Metastatic Prostate ... Treatment with pembrolizumab led to a significant rate of biochemical and radiographic response in a heavily pre-treated cohort of MSI-H metastatic prostate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7186583/

Pembrolizumab for Treatment-Refractory Metastatic Castration ... Initial results from the first 10 patients with enzalutamide-resistant mCRPC who were treated with pembrolizumab in a phase II study showed a rapid decrease in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02861573

NCT02861573 | Study of Pembrolizumab (MK-3475) ... The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.165

Updated results of a phase Ib single-center study ... This study evaluated the safety and efficacy signals of pembrolizumab and chemotherapy in patients with small cell/neuroendocrine cancer of the prostate and ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00199-1/fulltext

the randomized, double-blind, phase III KEYNOTE-641 study The PSA response rate (95% CI) was 49.0% (44.9% to 53.1%) with pembrolizumab plus enzalutamide versus 45.1% (41.1% to 49.2%) with placebo plus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11892552/

Response to pembrolizumab in advanced prostate cancer ... We found that 38.9% of patients showed a 50% or greater decline in PSA, all of whom had high microsatellite instability (MSI-H). One patient ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02787005

NCT02787005 | Study of Pembrolizumab (MK-3475) in ... This is a study of pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer (mCRPC).