M9241 + SBRT for Prostate Cancer

Overseen By Willie C Jackson

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: ADT

Must not be taking: Systemic corticosteroids, Immunosuppressive medications

Disqualifiers: Metastatic disease, Previous prostatectomy, Autoimmune diseases, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, M9241, to determine if it can help the immune system fight prostate cancer. The goal is to identify safe doses of M9241 and understand its effects on the immune system when combined with standard treatments like Stereotactic Body Radiation Therapy (SBRT) and hormone therapy. Participants should have prostate cancer confined to the prostate and require radiation and hormone therapy. The trial will explore different doses of M9241 alongside these treatments to determine the most effective combination. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or immunosuppressive medications, you may need to adjust your treatment, as these are generally not allowed unless they are low-dose or inhaled steroids.

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

Research has shown that M9241 is generally safe and well-tolerated in patients with prostate cancer. In one study, 5 out of 8 patients experienced a drop in PSA levels, a marker used to evaluate prostate cancer. About 21% of patients experienced serious side effects related to the treatment when M9241 was combined with another drug, a common occurrence in cancer treatments.

Stereotactic Body Radiation Therapy (SBRT) is also considered safe and effective for prostate cancer, with a strong safety record. Over five years, some patients reported urinary issues, similar to those experienced by patients receiving standard radiation therapy. Most patients handle SBRT well, and it shows promising results in treating localized prostate cancer.

Both treatments are part of ongoing research aimed at improving prostate cancer care. ^{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 to improve outcomes. Unlike standard treatments like hormone therapy and surgery, M9241, a novel immunotherapy, is used alongside Stereotactic Body Radiation Therapy (SBRT) to potentially enhance the body's immune response against cancer cells. Arm 1 explores de-escalating doses of M9241 with SBRT, potentially reducing side effects while maintaining effectiveness. Arm 2a tests the highest tolerated dose of M9241 with SBRT, aiming for maximum therapeutic impact. Arm 2b examines SBRT alone, providing a basis for comparing the added benefits of M9241. This multi-approach trial could lead to more personalized and effective treatment strategies for prostate cancer.

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

Research has shown that the new drug M9241 could effectively treat prostate cancer. In studies, it was safe and well-tolerated, with some patients experiencing lower PSA levels, a marker used to track prostate cancer. M9241 enhances the immune system's ability to fight cancer cells. In this trial, some participants will receive M9241 combined with Stereotactic Body Radiation Therapy (SBRT), while others will receive SBRT alone.

SBRT has demonstrated impressive results, with 83.6% of patients remaining cancer-free for at least five years after treatment. It provides effective symptom relief without severe side effects. Together, these treatments offer a promising approach to managing prostate cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Men over 18 with intermediate or high-risk prostate cancer that hasn't spread are eligible. They need to have certain levels of blood cells, liver and kidney function, and agree to use contraception. Excluded are those with HIV, active hepatitis, other recent cancers (except some skin/cervical/breast/prostate), previous prostate treatments, immune deficiencies/autoimmune diseases, allergies to M9241 or SBRT contraindications.

Inclusion Criteria

My prostate cancer can be biopsied.

I am a man aged 18 or older.

Testosterone greater than 100 ng/dL

Exclusion Criteria

I don't have conditions like inflammatory bowel disease that prevent SBRT.

I have started hormone therapy or radiation treatment before joining this trial.

I haven't had any cancer except for treatable ones in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation Therapy

Participants receive Stereotactic Body Radiation Therapy (SBRT) along with Androgen Deprivation Therapy (ADT)

4 weeks

Weekly visits (in-person)

Immunotherapy Treatment

Participants receive M9241 injections every 4 weeks for 3 doses, starting 4 weeks after radiation ends

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• M9241
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The trial tests if the drug M9241 can boost the immune system against prostate cancer when added to standard radiation therapy and ADT. Participants will receive either just radiation and ADT or these plus three doses of M9241 injections after radiation ends. The study lasts 7 months with follow-ups for safety and effectiveness.

How Is the Trial Designed?

Group I: 3/Arm 2b Experimental Treatment 1 Intervention

SBRT

Group II: 2/Arm 2a Experimental Treatment 2 Interventions

Highest tolerated dose of M941+SBRT

Group III: 1/Arm 1 Experimental Treatment 2 Interventions

De-escalating doses of M9241 if appropriate + SBRT

Stereotactic Body Radiation Therapy (SBRT) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in European Union as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in Canada as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in Japan as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 23 patients with high-risk prostate cancer, stereotactic body radiation therapy (SBRT) was found to be feasible and well tolerated, with low rates of severe gastrointestinal (GI) and genitourinary (GU) toxicities.

The treatment resulted in acute grade 1 GI toxicities in only 9.1% of patients and grade 3 GU toxicities in 4.5%, indicating that serious side effects were uncommon, but further long-term follow-up is needed to assess ongoing safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. Pinitpatcharalert, A., Happersett, L., Kollmeier, M., et al.[2022]

In a study of 26 patients with low- or intermediate-risk prostate adenocarcinoma, stereotactic body radiation therapy (SBRT) showed excellent biochemical control with no observed failures after a median follow-up of 59.5 months.

The treatment resulted in manageable late toxicity, with only 11.5% of patients experiencing significant genitourinary or gastrointestinal side effects, and patient-reported quality of life remained stable compared to pre-treatment levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial. Maas, JA., Dobelbower, MC., Yang, ES., et al.[2023]

Stereotactic body radiotherapy (SBRT) is a recognized treatment for low- and intermediate-favorable risk prostate cancer, but its effectiveness for unfavorable and high-risk cases is less established.

The review highlights the complexity of comparing SBRT techniques due to the various treatment variations reported, indicating a need for more solid evidence in high-risk prostate cancer applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the current role of stereotactic body radiotherapy in the treatment of unfavorable intermediate- and high-risk prostate cancer. Mezeckis, M., Danny, V., Vladyslav, B., et al.[2023]

The use of stereotactic body radiation therapy (SBRT) for low and intermediate risk prostate cancer increased dramatically from 0.9% in 2004 to 19.5% in 2015, indicating growing acceptance of this treatment method.

SBRT has been shown to have a favorable toxicity profile and efficacy, leading to a significant decline in conventional fractionation treatments, which dropped from 96.3% to 75.8% during the same period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current use of stereotactic body radiation therapy for low and intermediate risk prostate cancer: A National Cancer Database Analysis. Malouff, TD., Stross, WC., Seneviratne, DS., et al.[2021]

In a study of 28,028 men with unfavorable-intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) was associated with improved overall survival compared to conventionally fractionated radiotherapy (CFRT) without androgen deprivation therapy (ADT), suggesting its effectiveness as a treatment option.

SBRT offers a shorter and less expensive treatment course, which may reduce patient exposure to COVID-19, and is recommended as a viable alternative for prostate cancer treatment, although further clinical trials are needed to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propensity-Weighted Survival Analysis of SBRT vs. Conventional Radiotherapy in Unfavorable Intermediate-Risk Prostate Cancer. Andruska, N., Fischer-Valuck, BW., Agabalogun, T., et al.[2023]

Stereotactic body radiotherapy (SBRT) for patients with metastatic castration-resistant prostate cancer (mCRPC) and oligoprogression (≤ 5 metastases) during androgen receptor-targeted therapy (ARTT) showed promising outcomes, with median time to next-line systemic treatment of 16.97 months and overall survival of 38.3 months based on a study of 34 patients.

The treatment was found to be safe, as no patients experienced significant toxicity (grade ≥ 2), indicating that SBRT can be an effective option for managing disease progression in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy. Ingrosso, G., Detti, B., Fodor, A., et al.[2021]

In a phase II study involving 55 patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions demonstrated a high 3-year biochemical control rate of 89.8%, indicating its efficacy in managing the disease.

The treatment was generally safe, with only 9% of patients experiencing acute grade 2 genitourinary toxicities and 11% experiencing gastrointestinal toxicities, while no severe grade 3 or higher toxicities were reported. Quality of life scores showed a slight decrease during treatment but recovered within 3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer. Kawakami, S., Tsumura, H., Satoh, T., et al.[2022]

In a study of 174 hormone-naïve patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT), significant urinary symptoms were reported more frequently than bowel symptoms, with 51.6% of patients experiencing a clinically significant decline in urinary scores at 12 months.

The study indicates that while urinary and bowel symptoms initially increased after treatment, the proportion of patients reporting significant declines in these symptoms decreased from 12 to 36 months, suggesting potential late improvements in quality of life following SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Prostate Cancer: What is the Appropriate Patient-Reported Outcome for Clinical Trial Design? Woo, JA., Chen, LN., Wang, H., et al.[2020]

Stereotactic body radiotherapy (SBRT) for low- and intermediate-risk prostate cancer patients was found to be safe and well-tolerated, with mild acute toxicity reported in only a small number of cases (23 out of 72 for rectal and 50 out of 72 for urinary issues).

Patient-reported quality of life remained stable over the first year post-treatment, with minimal changes in urinary, rectal, sexual, and hormonal scores, indicating that SBRT does not significantly impact these aspects of life in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy with flattening filter-free beams for prostate cancer: assessment of patient-reported quality of life. Scorsetti, M., Alongi, F., Clerici, E., et al.[2021]

Stereotactic body radiotherapy (SBRT) is emerging as a treatment option for localized prostate cancer, but the evidence supporting its use is still incomplete due to variability in clinical studies.

There is inconsistency in treatment techniques, target volumes, and dose constraints across different studies, highlighting the need for standardized protocols in SBRT for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly hypofractionated schedules for localized prostate cancer: Recommendations of the GETUG radiation oncology group. Lapierre, A., Hennequin, C., Beneux, A., et al.[2022]

Stereotactic body radiotherapy (SBRT) for localized prostate cancer shows promising results, with studies indicating that ultra-hypofractionated schedules (like 42.7 Gy in 7 fractions) are non-inferior to standard treatments in terms of 5-year biochemical recurrence-free survival and have similar tolerability.

Current evidence suggests that two-fraction SBRT may be the shortest effective treatment schedule, but caution is advised against single-fraction SBRT due to concerns about inferior efficacy, highlighting the need for ongoing trials to determine optimal fractionation schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus? Ong, WL., Loblaw, A.[2023]

Stereotactic body radiation therapy (SBRT) resulted in significantly lower post-treatment PSA levels compared to intensity-modulated radiation therapy (IMRT) at 2 and 3 years, indicating better efficacy in controlling prostate cancer.

Both SBRT and IMRT showed similar overall survival rates after 5 years, but SBRT offers advantages such as lower cost and easier application, making it a suitable alternative for treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy versus conventional intensity-modulated radiation therapy for the treatment of prostate cancer]. Gao, QN.[2022]

Stereotactic body radiotherapy (SBRT) is shown to be safe and effective for treating node-positive prostate cancer, with a median follow-up of 30 months revealing no severe gastrointestinal toxicities and manageable genitourinary side effects.

In a study of 60 patients, SBRT resulted in a 3-year overall survival rate of 89% and a biochemical failure-free survival rate of 77%, indicating promising long-term outcomes even in patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. Telkhade, T., Murthy, V., Kanala, TS., et al.[2021]

A study involving 803 patients analyzed the quality of life (QOL) impacts of SBRT, IMRT, and brachytherapy for localized prostate cancer, showing that all treatments resulted in good QOL two years post-treatment.

SBRT demonstrated similar outcomes to IMRT in urinary and sexual domains, but showed a significant improvement in bowel symptoms compared to brachytherapy, suggesting it may be a safer option with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy. Evans, JR., Zhao, S., Daignault, S., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.127

The immunocytokine M9241 in the treatment of prostate ... Conclusions: M9241 was found to be safe and well tolerated in PCa pts. PSA declines occurred in 5 of 8 evaluable pts. As with the phase 1 study, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10230972/

First-in-human phase Ib trial of M9241 (NHS-IL12) plus ... Data from this first-in-human phase Ib trial show that the combination of M9241 plus avelumab was generally well tolerated with a manageable ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT374270

Combining IL-12 immunocytokine (M9241) with docetaxel ... M9241 was well-tolerated as a monotherapy in a Phase I study with solid tumors (Strauss J, CCR 2019). Additional preclinical data has demonstrated synergy of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04633252

Study Details | NCT04633252 | M9241 in Combination ... Background: A phase III trial demonstrated that combining docetaxel and androgen deprivation therapy (ADT) significantly improved survival (57.6 vs 44.0 months ...

5. academic.oup.com academic.oup.com/oncolo/article/28/4/364/6987628

A Phase I Single-Arm Study of Biweekly NHS-IL12 in Patients ... Results of a previously reported phase I trial showed that monthly NHS-IL12 had an acceptable safety profile. This trial was expanded to include a biweekly.

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.093

Safety evaluation of M9241 in combination with docetaxel ... Conclusions: We established a safe dose-level of M9241 at ≥ 12mcg/kg. Updated clinical data from the safety cohort (n = 18) will be presented.