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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 : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH )

Brief Summary:
Open-label, multicenter, dose titration and expansion three-arm trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of W_pro1 cancer vaccine (W_pro1) in patients with metastatic castration resistant prostate cancer (mCRPC) W_pro1 in combination with goserelin acetate with or without cemiplimab, in patients with high-risk, localized prostate cancer (LPC)

Condition or disease Intervention/treatment Phase
Prostate Cancer Biological: W_pro1 Drug: Cemiplimab Drug: Goserelin acetate Phase 1 Phase 2

Detailed Description:
  • W_pro1 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 W_pro1 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 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 in Patients With Metastatic Castration Resistant Prostate Cancer and W_pro1 in Combination With Cemiplimab and/or Goserelin Acetate in Patients With High-risk, Localized 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

Arm Intervention/treatment
Experimental: Part 1 (mCRPC) - dose titration
W_pro1 monotherapy
Biological: W_pro1
Intravenous bolus injection

Experimental: Part 2 Arm 1 (mCRPC) - expansion cohort
W_pro1 monotherapy
Biological: W_pro1
Intravenous bolus injection

Experimental: Part 2 Arm 2 (LPC) - expansion cohort
W_pro1 in combination with cemiplimab and goserelin acetate
Biological: W_pro1
Intravenous bolus injection

Drug: Cemiplimab
Intravenous infusion

Drug: Goserelin acetate
Subcutaneous injection

Experimental: Part 2 Arm 3 (LPC) - expansion cohort
W_pro1 in combination with goserelin acetate
Biological: W_pro1
Intravenous bolus injection

Drug: Goserelin acetate
Subcutaneous injection




Primary Outcome Measures :
  1. Occurrence of dose limiting toxicities (DLTs) [ Time Frame: 21 Days ]
    Occurrence of DLTs during DLT observation period (first cycle of part 1)

  2. Occurrence of adverse events (AEs) [ Time Frame: up to 24 months ]
    Occurrence of AEs reported by relationship, grade, and seriousness according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0)


Secondary Outcome Measures :
  1. Change in numbers of W_pro1 antigen-specific T cells [ Time Frame: up to 24 months ]
    Occurrence of de novo induction or increase of W_pro1 antigen-specific T cells in peripheral blood compared to baseline

  2. 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 the Prostate Cancer Working Group 3 [PCWG3]

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

  4. Change in prostatic acid phosphatase (PAP) levels [ Time Frame: up to 24 months ]
    PAP levels during treatment and at end of treatment (EOT) compared to baseline



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

Main 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 score of 0 or 1.

Specific key inclusion criteria for mCRPC patients:

  • 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:

  • Treatment-naïve patients with high-risk LPC (ie, N0, M0) defined according to European Association of Urology Guidelines on Prostate Cancer (2018). Patients must have at least 1 of the following:

    1. PSA >20 ng/mL or
    2. Gleason Score >7 or
    3. Localized stage ≥cT2b, 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:

  • Patients with uncontrolled intercurrent illness.
  • Patients with a known history or current malignancy other than the inclusion diagnosis. Note: Patients with non-invasive basal cell or 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 (testing not required):

    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/medication:

    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 for any non-cancer disease within 4 weeks or 5 half-lives of the agent (whichever is shorter) before the first dose of investigational medicinal product (IMP).
    3. Prior treatment with live-attenuated vaccines within 4 weeks before the first dose of IMP during treatment, and for 3 months after the last dose of W_pro1.
    4. Prior treatment with an investigational drug (including investigational vaccines) within 4 weeks or 5 half-lives of the agent (whichever is shorter) before the planned first dose of IMP.
    5. 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.
    6. Concurrent use of herbal products that may decrease PSA levels (e.g., saw palmetto).

Specific key exclusion criteria for mCRPC patients:

Excluded medical conditions

  • Patients with toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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 W_pro1 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 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 shorter] 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 PD-1, programmed cell death 1 ligand 1 (PD-L1), tumor necrosis factor receptor superfamily member 9 (TNRSF9, 4-1BB, CD137), tumor necrosis factor receptor superfamily member 4 (OX-40), therapeutic vaccines, cytokine treatments, or any investigational agent within 4 weeks before the first dose of IMP.

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 1919 patients@biontech.de
Contact: BioNTech clinical trial information desk +49 6131 9084 ext 0 info@biontech.de

Locations
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Germany
Universitätsklinikum Münster Not yet recruiting
Münster, Germany, 48149
Studienpraxis Urologie Not yet recruiting
Nürtingen, Germany, 72622
Universitätsklinikum Tübingen Not yet recruiting
Tübingen, Germany, 72076
Hungary
Magyar Honvédség Egészségügyi Központ (MH EK Honvédkórház) Recruiting
Budapest, Hungary, 1062
Semmelweis Egyetem, Belgyógyászati Klinika Recruiting
Budapest, Hungary, 1083
Onkológiai Klinika Not yet recruiting
Debrecen, Hungary, 4032
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház Not yet recruiting
Nyíregyháza, Hungary, 4400
University of Pecs Not yet recruiting
Pecs, Hungary, 7624
Szent Borbála Kórház Not yet recruiting
Tatabánya, Hungary, 2800
United Kingdom
Cancer Research UK Cambridge Centre Not yet recruiting
Cambridge, United Kingdom, CB2 0RE
Velindre Cancer Centre (VCC) Not yet recruiting
Cardiff, United Kingdom, CF14 2TL
University of Glasgow, Beatson WoS Cancer Centre Not yet recruiting
Glasgow, United Kingdom, G12 0YN
University College London Hospitals Recruiting
London, United Kingdom, NW1 2PG
The Royal Marsden Hospital Not yet recruiting
London, United Kingdom, SW3 6JJ
Derriford Hospital Not yet recruiting
Plymouth, United Kingdom, PL68DH
University Hospital Southampton - Southampton General Hospital Not yet recruiting
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
BioNTech RNA Pharmaceuticals GmbH
Investigators
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Study Director: BioNTech Responsible Person BioNTech SE
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Responsible Party: BioNTech RNA Pharmaceuticals GmbH
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: May 19, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH ):
Prostate cancer
PRO-MERIT
Cancer vaccine
W_pro1
BioNTech RNA Pharmaceuticals GmbH
RNA
mCRPC
LPC
Goserelin acetate
Cemiplimab
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Goserelin
Cemiplimab
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Immunological