A Phase II Study Evaluating T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine M9241 in Localized High and Intermediate Risk Prostate Cancer Treated With Androgen Deprivation Therapy

  • End date
    Dec 1, 2024
  • participants needed
  • sponsor
    National Cancer Institute (NCI)
Updated on 24 October 2022



Prostate cancer is often treated with radiation and ADT (ADT is androgen deprivation therapy). Up to 30% of these cancers recur within 5 years of treatment. Researchers want to see if a new drug (M9241) can help the immune system to fight prostate cancer.


To find what doses of M9241 are safe in people who are treated for prostate cancer. Also, to see what effects M9241 has on the immune system.


People aged 18 and older with high- and intermediate-risk prostate cancer. Their cancer must not have spread to other parts of the body.


The study will last 7 months.

Participants will be screened. They will share their medical history. They will also have:

<TAB>A physical exam

<TAB>Routine blood and urine tests

<TAB>Imaging scans of the chest, abdomen, and pelvis

<TAB>A bone scan

<TAB>A tumor biopsy

<TAB>A specialized MRI. Participants will lie face down on the MRI scanner table. An antenna that receives a signal may be placed in the rectum.

All participants will be treated with radiation therapy and ADT.

Some participants will also receive M9241 as an injection under the skin. This treatment will start 4 weeks after the radiation has ended. Participants will receive a total of 3 doses. The injections will be 4 weeks apart. Some screening tests will be repeated at each visit.

Participants who do not receive M9241 will also have screening tests during the treatment period.

Participants will return for follow-up about 1 month after the last treatment or set of tests.


  • Patients with intermediate and high risk localized prostate cancer often receive radiotherapy with androgen deprivation therapy as a potentially curative treatment. With any local treatment for prostate cancer (radiation or surgery), as many as 20-30% of these intermediate and high risk patients will eventually develop biochemical recurrence within 5 years of treatment.
  • There is a growing body of evidence suggesting that stereotactic body radiation therapy (SBRT), which delivers highly conformal high-dose radiation, can promote anti-tumor immune responses both locally and systemically as well as synergize with immune checkpoint inhibitors and other forms of immunotherapy. SBRT is now considered a reasonable alternative to conventional fractionated external beam radiation therapy (EBRT) by the National Comprehensive Cancer Network (NCCN) guidelines and has rapidly proliferated in clinical use.
  • M9241 (NHS-IL12) is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both singleand double-stranded DNA (dsDNA) allowing for targeted delivery of proinflammatory cytokine, IL-12, to necrotic portions of tumor at sites of DNA exposure to promote local immunomodulation.
  • SBRT-induced dsDNA breaks are tumoricidal and may promote immunogenicity. SBRT also upregulates PD-L1 expression and leads to activation of TGF-Beta. SBRT may enhance intratumoral binding of DNA damage localizing agent, M9241. Preclinical models have demonstrated impressive synergy with radiation plus M9241.
  • This study will evaluate the proof of concept that immunocytokines can synergize with standard radiation + ADT in prostate cancer with a focus on T-cell clonality.
  • Safety Lead-In: To determine the safety and tolerated doses of the immunocytokine M9241 and Stereotactic Body Radiation Therapy (SBRT) in participants with localized high and intermediate risk prostate cancer receiving standard of care Androgen Deprivation Therapy (ADT)
  • To evaluate T-cell clonality, as a measure of immunologic activity, after treatment with SBRT alone or in combination with immunotherapy agent M9241 in participants with prostate cancer receiving standard of care ADT
  • Participants with intermediate or high risk localized prostate cancer
  • Participants with no history of prior radiation to the prostate or prior prostatectomy
  • Participants without autoimmune disease or history of bleeding disorder
  • Participants with adequate organ and bone marrow function
  • This is an open label, randomized, Phase II trial evaluating T-cell clonality after treatment with SBRT alone or in combination with immunotherapy agent M9241in participants with localized intermediate or high risk prostate cancer receiving standard of care ADT.
  • The trial will begin with a safety lead-in cohort with de-escalating doses of M9241 (starting dose 16.8 mcg/kg, and de-escalated if needed to 12 mcg/kg, or 8 mcg/kg) only if needed, to evaluate safety and tolerability of the combination of treatments.
  • ADT will be administered to all participants on the study as standard care.
  • Those participants receiving immunotherapy agents will receive M9241 by subcutaneous injection (sc) at a dose determined during the safety lead-in, every 4 weeks for 3 doses.
  • To account for 3 inevaluable participants and 10 screen failures, the accrual ceiling has been set at 65 participants (18 participants during the safety lead-in phase, 34 during the randomized phase II portion).

Condition Cancer Of Prostate
Treatment Stereotactic Body Radiation Therapy (SBRT), M9241
Clinical Study IdentifierNCT05361798
SponsorNational Cancer Institute (NCI)
Last Modified on24 October 2022


Yes No Not Sure

Inclusion Criteria

Participants must have histologically or cytologically confirmed localized intermediate or high risk prostate cancer
Intermediate risk - Gleason 7 disease, PSA less than 10
High Risk - Gleason 8-10, PSA>10, Extracapsular Extension
Participants must require treatment with SBRT to the prostate and ADT
Pre-treatment tissue availability (collected <= 1 year to initiation of study therapy) for biomarker analysis is mandatory for enrollment. If tissue is determined to be of insufficient/unsuitable quality/quantity, a pre-treatment biopsy prior to initiation of study therapy will be required
Male age >= 18 years old
ECOG performance status < 2
Participants must have adequate organ and marrow function as defined below
absolute neutrophil count >= 1,500/mcL, without CSF support
platelets >= 100,000/mcL
AST(SGOT)/ALT(SGPT) <= 2.5 X institutional upper limit of normal
Hgb >= 10g/dL (pRBC transfusions are not allowed to achieve acceptable Hgb)
Total bilirubin <= 1.5 x upper limit of normal (ULN)
in participants with Gilbert s syndrome, a total bilirubin <= 3.0
Serum albumin >= 2.8 g/dL
Creatine <= 1.5 X institutional ULN
Creatinine clearance >= 50 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal by 24h urine
PT/INR and aPTT <= 1.5 X institutional ULN
Testosterone greater than 100 ng/dL
Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) after study entry and for 6 months after completion of radiation treatment or immunotherapy (if taken, whatever is last)
Participants must have prostate cancer accessible for biopsy
Ability of participant to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Evidence of distant metastatic disease (including clinically or pathologically positive lymph nodes or metastatic disease outside of the pelvis)
Previous prostatectomy, focal therapy, or radiation to the prostate. Note: Previous finasteride, dutasteride, bicalutamide are allowed at PI discretion
Initiation of ADT or SBRT or pelvic nodal radiation irradiation prior to trial enrollment (no time limit)
Live vaccine therapies for the prevention of infectious disease within 30 days prior to treatment administration. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted
Contraindication to mpMRI including allergy or sensitivity to contrast agents (which cannot be alleviated by premedication)
Contraindications for SBRT such as: rectal wall invasion, history of inflammatory bowel disease, prior radiation in the treatment field that would exceed tissue tolerance
Medical comorbidities that preclude the administration of androgen deprivation therapy or uncontrolled chronic or acute intercurrent illness /social situations or other illnesses considered by the Investigator as high risk for investigational drug treatment
Participants with active immune deficiencies, chronic inflammatory conditions, active autoimmune diseases, or participants on chronic immunosuppressive therapy for whom the primary endpoint of immune response could be impacted
Participants requiring requiring systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications except inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or dose not threaten vital organ function including CN, heart, lungs, kidneys, skin and GI track will be allowed
Participants with HIV
Active Hepatitis B or Hepatitis C infection
Significant acute or chronic infections including tuberculosis (history of exposure or history of positive tuberculosis test; plus, presence of clinical symptoms, physical or radiographic findings)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to M9241
Participants with prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast or low risk Gleason 6 prostate cancer
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note