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PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy) (PRO-MERIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04382898
Recruitment Status : Recruiting
First Posted : May 11, 2020
Last Update Posted : March 14, 2023
Sponsor:
Information provided by (Responsible Party):
BioNTech SE

Study Description
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Brief Summary:

Open-label, multicenter, dose titration and four-arm expansion trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of BNT112 cancer vaccine (BNT112) monotherapy or in combination with cemiplimab in patients with metastatic castration resistant prostate cancer (mCRPC: Part 1 and Part 2 Arms 1A and 1B) and in patients with high-risk, localized prostate cancer (LPC).

As of February 2023, the trial will be only recruiting LPC patients and no longer mCRPC patients.


Condition or disease Intervention/treatment Phase
Prostate Cancer Biological: BNT112 Drug: Cemiplimab Phase 1 Phase 2

Detailed Description:
  • BNT112 consists of messenger ribonucleic acid (mRNA [or RNA]) targeting 5 antigens expressed in de novo and metastatic prostate cancer that are separately complexed with liposomes to form serum-stable RNA lipoplexes (RNA-LPX).
  • The RNA molecules are immune-pharmacologically optimized for high stability, translational efficiency and presentation on major histocompatibility complex (MHC) class I and II molecules. The vaccine is intended for intravenous (IV) bolus injection.
  • The RNA-LPX cancer vaccine induces activation of both the adaptive immune system (vaccine antigen-specific CD8+/CD4+ T cell) as well as the innate immune system (TLR7 agonism of single-stranded RNA). The physiology of efficient induction, expansion and differentiation of antigen-specific T cells is associated with programmed death receptor-1 (PD-1) upregulation on these T cells. Thus, the cancer vaccine is expected to have a synergistic mechanism of action with anti-PD-1.
  • In summary, the mechanism of action of BNT112 both in monotherapy and in combination with anti-PD-1 immune checkpoint inhibitor cemiplimab, together with carefully selected and refined clinical setting presents a unique opportunity for patients with different stages of prostate cancer.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: First-in-human, Dose Titration and Expansion Trial to Evaluate Safety, Immunogenicity and Preliminary Efficacy of W_pro1 (BNT112) Monotherapy and in Combination With Cemiplimab in Patients With Prostate Cancer
Actual Study Start Date : December 19, 2019
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 (mCRPC) - dose titration

BNT112 monotherapy

Enrollment into this arm is completed.

 Biological: BNT112
Intravenous bolus injection
Experimental: Part 2 Arm 1A (mCRPC) - expansion cohort

BNT112 in combination with cemiplimab

Enrollment into this arm is completed.

 Biological: BNT112
Intravenous bolus injection

Drug: Cemiplimab
Intravenous infusion
Experimental: Part 2 Arm 1B [1] (mCRPC) - expansion cohort

BNT112 monotherapy

Enrollment into this arm is completed.

 Biological: BNT112
Intravenous bolus injection
Experimental: Part 2 Arm 2 (LPC) - expansion cohort
BNT112 in combination with cemiplimab
 Biological: BNT112
Intravenous bolus injection

Drug: Cemiplimab
Intravenous infusion
Experimental: Part 2 Arm 3 (LPC) - expansion cohort
BNT112 monotherapy
 Biological: BNT112
Intravenous bolus injection
Experimental: Part 2 Arm 1B [2] (mCRPC) - expansion cohort

Following progression after BNT112 monotherapy, patients in Arm 1b have the option to be treated with cemiplimab monotherapy

Enrollment into this arm is completed.

 Drug: Cemiplimab
Intravenous infusion


Outcome Measures
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Primary Outcome Measures :
  1. Occurrence of dose limiting toxicities (DLTs) [ Time Frame: up to 24 months ]
  2. Occurrence of treatment-emergent adverse events (TEAEs) [ Time Frame: up to 24 months ]
    Occurrence of TEAEs reported by relationship, grade, and seriousness according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0).

  3. Objective response rate (ORR) - Part 2 Arms 1A and 1B [ Time Frame: up to 24 months ]
    ORR, defined as the number of patients with a complete response (CR) or partial response (PR) per Prostate Cancer Working Group 3 (PCWG3).


Secondary Outcome Measures :
  1. Change in prostate-specific antigen (PSA) levels [ Time Frame: up to 24 months ]
    PSA decline of 0 to 25%, >25% to 50%, and >50% compared to baseline, as well as PSA decline ≥ 50% according to PCWG3.

  2. Change in PSA doubling time (PSADT) [ Time Frame: up to 24 months ]
    PSADT during treatment and end of treatment (EoT) compared to baseline.

  3. ORR - Part 1 [ Time Frame: up to 24 months ]
    ORR, defined as the number of patients with a CR or PR per PCWG3.

  4. Tumor response post-treatment compared to baseline [ Time Frame: up to 24 months ]
    Evaluate preliminary anti-tumor activity of BNT112 monotherapy or in combination with cemiplimab in patients with newly diagnosed LPC.


Eligibility Criteria
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Information from the National Library of Medicine

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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:

  • Patients must be male and aged ≥18 years.
  • Patients must have histologically confirmed prostate adenocarcinoma.
  • Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.

Specific key inclusion criteria for mCRPC patients (Part 1 and Part 2 Arms 1A and 1B) - Recruitment of mCRPC patients now completed:

  • Patients must have histologically confirmed mCRPC and have progressed after at least 2 but no more than 3 lines of life-prolonging systemic therapy (e.g., abiraterone or enzalutamide, docetaxel, cabazitaxel) or cannot tolerate or have refused any of these therapies. These lines of therapy include life-prolonging therapies administered in the metastatic hormone-sensitive setting.
  • Prior surgical or chemical castration with a serum testosterone <1.7 nmol/L (50 ng/dL). If the method of castration is luteinizing hormone-releasing hormone analogue (LHRHa), there must be a plan to maintain effective LHRHa therapy for the duration of the trial.
  • Patients must have documented mCRPC progression within 6 months prior to screening (assuming no subsequent change in treatments), as determined by the investigator.
  • Patients must agree to provide an archival pre-treatment formalin-fixed, paraffin-embedded tumor sample if available.

Specific key inclusion criteria for newly diagnosed LPC patients (Part 2 Arms 2 and 3):

  • Treatment-naïve patients with LPC (i.e., N0, M0). According to risk levels of the European Association of Urology Guidelines on Prostate Cancer (2018), and in line with the U.S. National Comprehensive Cancer Network (NCCN 2020), patients must have at least 1 of the following:

    1. PSA >20 ng/mL or
    2. Gleason Score >7 or
    3. Localized stage ≥cT2c, N0, M0 according to tumor, node, metastasis classification.
  • Patients who intend to have and are suitable for a radical prostatectomy.
  • Patients must agree to provide tumor sample(s) from pre-treatment diagnostic biopsy and planned post-treatment surgery.

Main exclusion criteria for all patients:

Medical conditions

  • Patients with uncontrolled intercurrent illness.
  • Patients with a known history or current malignancy other than the inclusion diagnosis. Note: Exceptions are patients with malignancies with a negligible risk of metastasis or death, that have been adequately treated, such as non-invasive basal cell or non-invasive squamous cell skin carcinoma, non-invasive, superficial bladder cancer, and any cancer with a complete response (CR) that lasted more than 2 years may be included.
  • Patients who have had major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, or have not fully recovered from surgery, or have a surgery planned during the time of trial participation, except for the radical prostatectomy planned for patients in Part 2 Arms 2 and 3.

  • Patients who have a known history of any of the following:

    1. Human immunodeficiency virus (HIV) 1 or 2
    2. Hepatitis B (carrier or active infection)
    3. Hepatitis C (unless considered cured 5 years post curative anti-viral therapy)

  • Patients who have received or currently receive the following therapy/treatment:

    1. Chronic systemic immunosuppressive corticosteroid treatment (prednisone >5 mg daily orally [PO] or IV, or equivalent) during the trial. Note: Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted.
    2. Prior treatment with other immune modulating agents that was (a) within fewer than 4 weeks (28 days) or 5 half-lives (whichever is longer) prior to the first dose of cemiplimab, or (b) associated with immune-mediated AEs that were Grade ≥1 within 90 days prior to the first dose of cemiplimab, or (c) associated with toxicity that resulted in discontinuation of the immune-modulating agent.
    3. Prior treatment with other immune modulating agents for any non-cancer disease within 4 weeks or 5 half-lives of the agent (whichever is longer) before the first dose of IMP.
    4. Prior treatment with live-attenuated vaccines within 4 weeks before the first dose of IMP and during treatment with IMP.
    5. Prior treatment with an investigational drug (including investigational vaccines) within 4 weeks or 5 half-lives of the agent (whichever is longer) before the planned first dose of IMP.
    6. Therapeutic PO or IV antibiotics within 14 days prior to enrollment. Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) may be enrolled.
    7. Concurrent use of herbal products that may decrease PSA levels (e.g., saw palmetto).

Specific key exclusion criteria for mCRPC Patients (Part 1 and Part 2 Arms 1A and 1B) - Recruitment of mCRPC patients now completed:

Excluded medical conditions

  • Patients with toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade ≤1 according to National Cancer Institute (NCI) CTCAE v5.0 with the exception of alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy must have recovered to Grade ≤2.

  • Patients with clinically active brain metastases.

    1. Patients with a history of symptomatic metastatic brain or meningeal tumors may be included, if the end of definitive therapy is >3 months before the first dose of BNT112 and the patients have no clinical or radiological evidence of tumor growth.
    2. Patients with brain metastases must not be undergoing acute or chronic corticosteroid therapy or steroid taper.
    3. Patients with central nervous system symptoms should undergo a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain to exclude new or progressive brain metastases. Spinal cord metastasis is acceptable. However, patients with spinal cord compression should be excluded.

Excluded prior or concomitant anti-cancer therapies

  • Patients who have received or currently receive the following anti-cancer therapy/agent:

    1. Prior radiation therapy with curative intent within 14 days before the first dose of IMP. Note: Palliative radiotherapy is allowed.
    2. Prior treatment with an anti-cancer agent (within 4 weeks or for systemic therapies after at least 5 half-lives of the drug [whichever is longer] before the first dose of IMP). Note: Prior treatment with bone resorptive therapy, such as bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab, is allowed assuming that the patients have been on stable doses for ≥4 weeks prior to first dose of trial treatment.
    3. Prior treatment with anti-cancer immunomodulating agents, such as blockers of programmed death receptor-1 PD-1, programmed cell death 1 ligand 1 (PD-L1), tumor necrosis factor receptor superfamily member 9 (TNRSF9, 4-1BB, CD137), OX-40, therapeutic vaccines, cytokine treatments, or any investigational agent within 4 weeks or 5 half-lives (whichever is longer) before the first dose of IMP.
Contacts and Locations
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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): NCT04382898


Contacts
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Contact: BioNTech clinical trials patient information +49 6131 9084 ext 0 patients@biontech.de

Locations
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Sponsors and Collaborators
BioNTech SE
Investigators
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Study Director: BioNTech Responsible Person BioNTech SE
More Information
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Responsible Party: BioNTech SE
ClinicalTrials.gov Identifier: NCT04382898    
Other Study ID Numbers: RN5609C00
2018-004321-86 ( EudraCT Number )
First Posted: May 11, 2020    Key Record Dates
Last Update Posted: March 14, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 BioNTech SE:
Prostate cancer
PRO-MERIT
Cancer vaccine
W_pro1
BioNTech SE
 RNA
mCRPC
LPC
Cemiplimab
BNT112
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
 Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents