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Bintrafusp Alfa (M7824) and M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT04633252
Recruitment Status : Recruiting
First Posted : November 18, 2020
Last Update Posted : July 28, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Metastatic castration sensitive and castration resistant prostate cancer (mCSPC and mCRPC) are prostate cancers that have spread to other parts of the body. Use of the drug docetaxel with androgen deprivation therapy can improve survival for men with mCSPC. Researchers want to see if combining this treatment with other drugs can help delay the time it takes for mCSPC and mCRPC to get worse.

Objective:

To learn if giving docetaxel with M7824 and M9241 is safe and effective for men with prostate cancer.

Eligibility:

Men age 18 and older with mCSPC or mCRPC.

Design:

Participants will be screened with a medical history and physical exam. Their diagnosis will be confirmed. Their symptoms and how well they do their normal activities will be reviewed. They will have blood and urine tests. Their heart will be evaluated. They will have imaging scans of the chest, abdomen, and pelvis. They will have bone scans with intravenous (IV) injections of Tc99 to check for tumor spread in the bones.

Some screening tests will be repeated during the study.

Participants may have tumor biopsies.

Participants will get treatment in cycles. Each cycle will last 21 days. They will get docetaxel and M7824 through IV infusion. They will get M9241 as an injection under the skin.

Participants with mCSPC will have up to 6 cycles. Those with mCRPC will be treated until they cannot tolerate the side effects or their disease gets worse.

Participants will have a follow-up visit 30 days after treatment ends. Those with mCSPC will then have follow-up visits at the clinic every 3 months....


Condition or disease Intervention/treatment Phase
Cancer Of Prostate Prostate Neoplasms Drug: ADT Drug: Prednisone Drug: M7824 Drug: Docetaxel Drug: M9241 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Bintrafusp Alfa (M7824) and M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer
Actual Study Start Date : February 23, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: 1/Dose Escalation
Docetaxel plus M9241 dose escalation with optional prednisone and ADT as part of SOC
Drug: ADT
For mCSPC patients: Androgen Deprivation Therapy (ADT) may include GnRH agonist or monthly degarelix converted to GnRH agonist after 3 months. For mCRPC patients: ADT will be continued as per standard of care.

Drug: Prednisone
For mCSPC patients, prednisone is optional and if given, should be taken orally, at 5 mg once a day. For mCRPC patients, prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day as is the patient s preference.

Drug: Docetaxel
Docetaxel 75mg/m^2 will be administered intravenously every 21 days (i.e., a 3-week cycle) for up to 6 cycles in mCSPC and until progression or unacceptable toxicity in mCRPC.

Drug: M9241
M9241 at escalating doses and then at RP2D will be administered as a subcutaneous injection every three weeks.

Experimental: 2/Safety Run-in
Docetaxel plus M9241 RP2D plus M7824 with optional prednisone and ADT as part of SOC
Drug: ADT
For mCSPC patients: Androgen Deprivation Therapy (ADT) may include GnRH agonist or monthly degarelix converted to GnRH agonist after 3 months. For mCRPC patients: ADT will be continued as per standard of care.

Drug: Prednisone
For mCSPC patients, prednisone is optional and if given, should be taken orally, at 5 mg once a day. For mCRPC patients, prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day as is the patient s preference.

Drug: M7824
M7824 (2400 mg) will be administered as a 1 hour intravenous (IV) infusion once every three weeks.

Drug: Docetaxel
Docetaxel 75mg/m^2 will be administered intravenously every 21 days (i.e., a 3-week cycle) for up to 6 cycles in mCSPC and until progression or unacceptable toxicity in mCRPC.

Drug: M9241
M9241 at escalating doses and then at RP2D will be administered as a subcutaneous injection every three weeks.

Experimental: 3/mCSPC: Dose Expansion
Docetaxel plus M9241 RP2D plus M7824 with optional prednisone and ADT as part of SOC
Drug: ADT
For mCSPC patients: Androgen Deprivation Therapy (ADT) may include GnRH agonist or monthly degarelix converted to GnRH agonist after 3 months. For mCRPC patients: ADT will be continued as per standard of care.

Drug: Prednisone
For mCSPC patients, prednisone is optional and if given, should be taken orally, at 5 mg once a day. For mCRPC patients, prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day as is the patient s preference.

Drug: M7824
M7824 (2400 mg) will be administered as a 1 hour intravenous (IV) infusion once every three weeks.

Drug: Docetaxel
Docetaxel 75mg/m^2 will be administered intravenously every 21 days (i.e., a 3-week cycle) for up to 6 cycles in mCSPC and until progression or unacceptable toxicity in mCRPC.

Drug: M9241
M9241 at escalating doses and then at RP2D will be administered as a subcutaneous injection every three weeks.

Experimental: 4/mCRPC: Dose Expansion
Docetaxel plus M9241 RP2D plus M7824 with optional prednisone and ADT as part of SOC
Drug: ADT
For mCSPC patients: Androgen Deprivation Therapy (ADT) may include GnRH agonist or monthly degarelix converted to GnRH agonist after 3 months. For mCRPC patients: ADT will be continued as per standard of care.

Drug: Prednisone
For mCSPC patients, prednisone is optional and if given, should be taken orally, at 5 mg once a day. For mCRPC patients, prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day as is the patient s preference.

Drug: M7824
M7824 (2400 mg) will be administered as a 1 hour intravenous (IV) infusion once every three weeks.

Drug: Docetaxel
Docetaxel 75mg/m^2 will be administered intravenously every 21 days (i.e., a 3-week cycle) for up to 6 cycles in mCSPC and until progression or unacceptable toxicity in mCRPC.

Drug: M9241
M9241 at escalating doses and then at RP2D will be administered as a subcutaneous injection every three weeks.




Primary Outcome Measures :
  1. To evaluate safety and tolerability of docetaxel in combination with M7824 and M9241 in patients who have metastatic prostate cancer. [ Time Frame: DLT observation period (until the end of 6 weeks) ]
    of the number and type of toxicities noted for participants who are evaluable for toxicity

  2. Determine clinical efficacy in adults with prostate cancer treated with docetaxel in combination with Anti-PD-L1/TGF-beta trap (M7824) and the immunocytokine, M9241 [ Time Frame: 4-8 weeks ]
    For castration sensitive: Increase in the proportion of participants who have less than 0.2 ng/ml of PSA. For castration resistant: Increase in median progression free survival


Secondary Outcome Measures :
  1. Evaluate radiographic response rates [ Time Frame: 4-8 weeks ]
    Tumor progression on scans

  2. Evaluate percentage of patients with a 50% PSA decline from baseline [ Time Frame: 4-8 weeks ]
    PSA levels

  3. Evaluate radiographic and biochemical time to progression for mCSPC patients [ Time Frame: 7 months ]
    PSA levels and tumor progression on scans



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Participants must have documented histopathological confirmation of prostate cancer. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
  • Participants must have metastatic disease, defined as at least one lesion on TC99 bone scan or at least one lesion that is measurable per, per RECIST 1.1.
  • mCSPC participants:
  • Participants must be within 134 days of starting ADT.
  • If participants are on ADT and responding, this may impact the findings on scans. Pre- treatment scans could be used to confirm that participants have metastatic high-volume disease in such cases.

    • For Cohorts 1 and 2, Dose escalation and Safety Run-in, only: mCSPC may have high or low volume disease.
    • For Cohort 3, Dose Expansion: mCSPC participants must have high volume disease (as defined by visceral lesion or 4 or greater bone lesions, at least one of which is beyond the spine and pelvis).
  • mCRPC participants:
  • Must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.
  • Must have not had progression while on docetaxel if given for mCSPC or within 3 months of completing docetaxel for mCSPC.
  • Progression defined as either rising PSA greater than 2.0 ng/ml or radiographic evidence of progression seen on CT scan or TC-99 bone scan.
  • Toxicities related to prior therapy, including surgery and/ or radiation, must have resolved to <= grade 1.
  • Men age >=18 years. Because no dosing or adverse event data are currently available on the use of M7824 and/or M9241in combination with docetaxel in participants <18 years of age, children are excluded from this study.
  • ECOG performance status 0-2.
  • Participants must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count >=1,500/mcL, without CSF support
  • Platelets >=100,000/mcL
  • Hemoglobin >9 g/dL
  • PT <= 1.5 x ULN
  • aPIT 1.5 x ULN
  • Total bilirubin <= upper limit of normal (ULN), OR in participants with Gilbert s syndrome, a total bilirubin <= 3.0
  • Serum albumin >=2.8 g/dL
  • AST(SGOT)/ALT(SGPT) <=1.5 X institutional upper limit of normal
  • Serum Creatinine OR Creatinine Clearance <= 1.5 X institutional upper limits of normal OR >=50 mL/min/1.73 m^2 calculated by eGFR in the clinical lab for participants with serum creatinine levels > 1.5 ULN
  • The effects of M7824 and/or M9241 in combination with docetaxel on the developing human fetus are unknown. For this reason and because docetaxel agents as well as other immuno-therapeutic agents used in this trial are known to be teratogenic, sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom)after enrollment on study , during the study treatment and for 3 months after the last dose of docetaxel or M7824 or M921, even if oral contraceptives are also used. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately and her partner should inform the study doctor immediately.
  • Ability of subject to understand and the willingness to sign a written informed consent document. Subject should be willing to travel to the NIH for follow-up visits.
  • Participants with prior immune checkpoint therapy are eligible to enroll upon PI discretion.

EXCLUSION CRITERIA:

  • Immunocompromised status due to:
  • Human immunodeficiency virus (HIV) positivity
  • Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
  • Other immunodeficiency diseases that in the opinion of the investigator could compromise the participants or limit treatment efficacy
  • Chronic administration (defined as daily or every other day for continued use > 14 days) of corticosteroids (>10 mg daily prednisone equivalent) deemed systemic by investigator within 28 days before the first treatment on-study treatment. Use of inhaled steroids, nasal sprays, and topical creams (for small body areas) including adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with participant s ability to carry out the treatment program.
  • Participants with radiation proctitis and bleeding episodes within 6 months of enrollment are excluded.
  • Current use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
  • Receipt of any investigational agent within 28 days (or 60 days for an antibody-based therapy) before the first planned dose of study drugs.
  • Participants who are positive for Hepatitis B surface antigen and/or Anti-Hepatitis C antibody
  • Uncontrolled hypertension (SBP>170/ DBP>105)
  • Participants unwilling to accept blood products as medically indicated.
  • Has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
  • Participants who have had prior docetaxel for mCRPC
  • Participants who have had progression within 3 months of completing docetaxel for mCSPC
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M7824 and/or M9241 investigational agents used in the study
  • The subject has had evidence within 2 years of the start of study treatment of another active malignancy which required systemic treatment (except for nonmelanoma skin cancers or carcinoma in situ of the bladder).
  • The subject has active brain metastases or epidural disease.
  • Participants with greater than or equal to grade 2 peripheral neuropathy (defined by CTCAE 5.0) at baseline.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04633252


Contacts
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Contact: Helen T Owens, R.N. (240) 760-7965 helen.owens@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ravi A Madan, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04633252    
Other Study ID Numbers: 210001
21-C-0001
First Posted: November 18, 2020    Key Record Dates
Last Update Posted: July 28, 2021
Last Verified: July 26, 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Chemoimmunotherapy
Anti PD-L1 TGF Beta-Trap
NHS IL-12
Check point inhibitor
Combination Therapy
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Prednisone
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal