M9241 + Docetaxel for Prostate Cancer

Overseen By Amy R Hankin, P.A.-C

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Anti-androgens

Must not be taking: 5-alpha reductase inhibitors

Disqualifiers: HIV, Autoimmune diseases, Hypertension, others

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

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks for mCSPC, variable for mCRPC

86 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining the drug docetaxel with a new treatment called M9241 (also known as NHS-IL12) can safely and effectively help men with prostate cancer that has spread. The focus is on two types of prostate cancer: metastatic castration-sensitive (mCSPC) and metastatic castration-resistant (mCRPC). Researchers aim to determine if this combination can delay cancer progression. Men with these specific types of prostate cancer who need or are already on specific hormone therapies may be suitable for this trial. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in prostate cancer treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as those for urinary symptoms like finasteride and dutasteride, and any drugs that affect PSA levels. You also cannot use medications that interact with specific liver enzymes (CYP3A4 and CYP2D6) within 14 days before starting the trial.

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

Research has shown that combining M9241 with docetaxel has been tested for safety. In these studies, a safe dose of M9241 was determined to be at least 12 micrograms per kilogram, as this amount did not cause severe side effects in the group tested. Participants tolerated the treatment well, suggesting it is safe for humans at this dose.

Docetaxel, when used with hormone therapy (ADT), has already been shown to help prostate cancer patients live longer. Although new combinations always require careful testing, the current data is encouraging. So far, the combination of M9241 and docetaxel appears well-tolerated, making it a potential option for those considering participation in a clinical trial for prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of M9241 and docetaxel for prostate cancer because it offers a novel approach to treatment. Unlike most treatments that rely solely on chemotherapy, M9241 is an investigational immunotherapy that boosts the body's immune response to target cancer cells more effectively. This combination aims to enhance the effectiveness of docetaxel, a standard chemotherapy drug, potentially improving outcomes for patients. By integrating an immune-stimulating component, this treatment could offer a more comprehensive attack on cancer cells compared to traditional options.

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

This trial will evaluate the combination of docetaxel with M9241 for treating prostate cancer. Research has shown that this combination may help treat prostate cancer, as it has led to noticeable tumor shrinkage and longer survival in previous studies. M9241 enhances the immune system's ability to fight cancer cells. Some patients also experienced lower PSA (prostate-specific antigen) levels, indicating less active cancer. Overall, this combination appears promising for treating advanced prostate cancer. ^{3 4 6 7 8}

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?

This trial is for men aged 18+ with metastatic prostate cancer, either castration sensitive or resistant. They must have good organ function and performance status, resolved prior therapy toxicities to a mild level, and agree to use contraception. Men previously treated with certain anti-androgens are eligible unless they've had recent disease progression on docetaxel.

Inclusion Criteria

- PT <= 1.5 x ULN

- Hemoglobin >9 g/dL

I am a man aged 18 or older.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to M9241 investigational agents used in the study

I have received docetaxel for metastatic castration-resistant prostate cancer.

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive docetaxel and M9241 in cycles of 21 days. mCSPC participants receive up to 6 cycles, while mCRPC participants continue until progression or unacceptable toxicity.

18 weeks for mCSPC, variable for mCRPC

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. mCSPC participants have follow-up visits every 3 months.

3 months for mCSPC, variable for mCRPC

Every 3 months (in-person) for mCSPC

Dose Escalation

M9241 dose is escalated from a starting dose of 12 mcg/kg to 16.8 mcg/kg along with docetaxel to ensure safety before larger participant enrollment.

Variable

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• M9241

Trial Overview

The study tests the safety and effectiveness of M9241 combined with docetaxel in treating advanced prostate cancer. Participants will receive cycles of treatment; those with sensitive cancer get up to 6 cycles, while those resistant continue until side effects become intolerable or their disease worsens.

How Is the Trial Designed?

Group I: 4/mCRPC: Dose Expansion Experimental Treatment 5 Interventions

Docetaxel plus M9241 RP2D with optional prednisone and ADT as part of SOC

Group II: 3/mCSPC: Dose Expansion Experimental Treatment 5 Interventions

Docetaxel plus M9241 RP2D with optional prednisone and ADT as part of SOC

Group III: 2/Safety Run-in (no longer applies; removed before enrollment) Experimental Treatment 5 Interventions

Docetaxel plus M9241 RP2D plus M7824 with optional prednisone and ADT as part of SOC

Group IV: 1/Dose Escalation Experimental Treatment 4 Interventions

Docetaxel plus M9241 dose escalation with optional prednisone and ADT as part of SOC

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

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

Docetaxel shows a 42% response rate in treating androgen-independent prostate cancer based on four Phase II studies, indicating its significant efficacy as a single-agent therapy.

Combining docetaxel with estramustine may enhance response rates but also increases toxicity, and ongoing Phase III studies are expected to clarify the best use of docetaxel in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. Beer, TM., El-Geneidi, M., Eilers, KM.[2018]

Docetaxel has shown significant effectiveness as a single agent in treating hormone refractory prostate cancer, achieving a 42% prostate-specific antigen response rate in four phase-II studies.

Combining docetaxel with estramustine may enhance the response rate, but it also increases the risk of toxicity, and further evaluation in ongoing phase-III studies will clarify its overall role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Significance of docetaxel in the chemotherapy of hormone-refractory prostate cancer]. Wolff, JM.[2018]

In a study of 47 men with metastatic castration-resistant prostate cancer (mCRPC), combining androgen deprivation therapy (ADT) with docetaxel chemotherapy (DTX) significantly improved radiographic progression-free survival (rPFS) compared to DTX alone, with median rPFS of 9.0 months versus 6.0 months.

While overall survival (OS) was similar between the two groups (42.0 months for DTX+ADT and 38.0 months for DTX), the study indicates that concurrent ADT with DTX is a beneficial strategy for improving disease control in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. Jang, HS., Koo, KC., Cho, KS., et al.[2018]

In a Phase I study involving 18 patients with high-risk prostate cancer, the addition of weekly docetaxel chemotherapy at a safe dose of 20 mg/m² to high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) was found to be safe, with no severe toxicities reported.

At a median follow-up of 2.2 years, the treatment resulted in a high biochemical progression-free survival rate of 94%, indicating promising efficacy for this triple-therapy regimen in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. Chen, RC., Rosenman, JG., Hoffman, LG., et al.[2019]

In a pilot study of 15 patients with hormone-refractory prostate cancer resistant to paclitaxel-based chemotherapy, docetaxel (DTX) showed activity, with 33.3% of patients experiencing a 50% or greater reduction in prostate-specific antigen levels.

Despite its effectiveness, DTX treatment was associated with significant toxicities, including severe anemia in 66.7% of patients, highlighting the need for further research to optimize treatment regimens and manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study. Urakami, S., Yoshino, T., Kikuno, N., et al.[2018]

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

Combining naftopidil with docetaxel (DTX) significantly enhances the inhibition of prostate cancer cell growth and induces more apoptosis in LNCaP and PC-3 cancer cells compared to DTX alone, as shown in animal models.

The study indicates that naftopidil not only adds to the effectiveness of DTX but also exhibits a synergistic effect, suggesting that this combination could lead to better clinical outcomes for patients with castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells. Ishii, K., Matsuoka, I., Kajiwara, S., et al.[2018]

In an updated analysis of the TAX 327 study involving 1,006 men with metastatic hormone-resistant prostate cancer, docetaxel administered every 3 weeks (D3P) showed a significant survival benefit compared to mitoxantrone (MP), with a median survival of 19.2 months for D3P versus 16.3 months for MP.

The survival advantage of D3P persisted across various patient subgroups, including age and baseline pain status, indicating its efficacy as a treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. Berthold, DR., Pond, GR., Soban, F., et al.[2022]

The combination of docetaxel (DTX) and the mTOR inhibitor temsirolimus (TEM) significantly enhances the anticancer effect in castration-resistant prostate cancer (CRPC) cells by inducing apoptosis and suppressing autophagy, with a 34% greater reduction in cell proliferation compared to higher doses of DTX alone.

In vivo studies showed that this combination treatment resulted in a 72% reduction in tumor growth after 14 days, indicating a promising strategy for improving chemotherapy outcomes in CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose Docetaxel Enhanced the Anticancer Effect of Temsirolimus by Overcoming Autophagy in Prostate Cancer Cells. Inamura, SO., Ito, H., Taga, M., et al.[2019]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e17033

Combining IL-12 immunocytokine (M9241) 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.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04633252

Study Details | NCT04633252 | M9241 in Combination ...

To learn if giving docetaxel with M9241 is safe and effective for men with prostate cancer. ... data demonstrates the potential anti-tumor synergy of M9241 ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10361896/

Exploiting docetaxel-induced tumor cell necrosis with ...

Significant antitumor activity and prolonged survival were observed in cohorts receiving docetaxel and NHS-IL-12 combination therapy in both the ...

4.

ascopubs.org

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

The immunocytokine M9241 in the treatment of prostate ...

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, increases in NK ...

5.

researchgate.net

researchgate.net/publication/358737295_Safety_evaluation_of_M9241_in_combination_with_docetaxel_in_metastatic_prostate_cancer

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.

6.

ascopubs.org

ascopubs.org/doi/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.

7.

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 ...

8.

clin.larvol.com

clin.larvol.com/trial-detail/NCT04633252

M9241 in Combination With Docetaxel in Adults ...

The trial is investigating the safety, immune responses and clinical activity of PDS0301 and docetaxel in metastatic castration-sensitive and castration- ...