PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy)
- Registration Number
- NCT04382898
- Lead Sponsor
- BioNTech SE
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 Arm 2 (LPC) - expansion cohort Cemiplimab BNT112 in combination with cemiplimab Part 2 Arm 1B [2] (mCRPC) - expansion cohort Cemiplimab Following progression after BNT112 monotherapy, patients in Arm 1b have the option to be treated with cemiplimab monotherapy Enrollment into this arm is completed. Part 2 Arm 3 (LPC) - expansion cohort BNT112 BNT112 monotherapy Part 1 (mCRPC) - dose titration BNT112 BNT112 monotherapy Enrollment into this arm is completed. Part 2 Arm 1A (mCRPC) - expansion cohort BNT112 BNT112 in combination with cemiplimab Enrollment into this arm is completed. Part 2 Arm 1B [1] (mCRPC) - expansion cohort BNT112 BNT112 monotherapy Enrollment into this arm is completed. Part 2 Arm 2 (LPC) - expansion cohort BNT112 BNT112 in combination with cemiplimab Part 2 Arm 1A (mCRPC) - expansion cohort Cemiplimab BNT112 in combination with cemiplimab Enrollment into this arm is completed.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) - Part 2 Arms 1A and 1B 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).
Occurrence of dose limiting toxicities (DLTs) up to 24 months Occurrence of treatment-emergent adverse events (TEAEs) 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).
- Secondary Outcome Measures
Name Time Method Change in prostate-specific antigen (PSA) levels 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.
Change in PSA doubling time (PSADT) up to 24 months PSADT during treatment and end of treatment (EoT) compared to baseline.
ORR - Part 1 up to 24 months ORR, defined as the number of patients with a CR or PR per PCWG3.
Tumor response post-treatment compared to baseline up to 24 months Evaluate preliminary anti-tumor activity of BNT112 monotherapy or in combination with cemiplimab in patients with newly diagnosed LPC.
Trial Locations
- Locations (22)
Cancer Research UK Cambridge Centre
🇬🇧Cambridge, United Kingdom
University of Glasgow, Beatson WoS Cancer Centre
🇬🇧Glasgow, United Kingdom
University of Miami Hospital & Clinics /Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Urologische Klinik Planegg
🇩🇪Planegg, Germany
University of Pittsburgh Cancer Inst.
🇺🇸Pittsburgh, Pennsylvania, United States
Urology San Antonio P.A.
🇺🇸San Antonio, Texas, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Universitätsklinikum Münster
🇩🇪Münster, Germany
Studienpraxis Urologie
🇩🇪Nürtingen, Germany
Klinikum der Johann Wolfgang Goethe-Universität
🇩🇪Frankfurt, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
🇭🇺Nyíregyháza, Hungary
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Magyar Honvédség Egészségügyi Központ (MH EK Honvédkórház)
🇭🇺Budapest, Hungary
Semmelweis Egyetem, Belgyógyászati Klinika
🇭🇺Budapest, Hungary
Onkológiai Klinika
🇭🇺Debrecen, Hungary
Szent Borbála Kórház
🇭🇺Tatabánya, Hungary
Velindre Cancer Centre (VCC)
🇬🇧Cardiff, United Kingdom
The Royal Marsden Hospital
🇬🇧London, United Kingdom
University College London Hospitals
🇬🇧London, United Kingdom
University Hospital Southampton - Southampton General Hospital
🇬🇧Southampton, United Kingdom
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