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 only recruited LPC patients and no longer mCRPC patients.
- Detailed Description
* BNT112 consisted of messenger ribonucleic acid (mRNA \[or RNA\]) targeting 5 antigens expressed in de novo and metastatic prostate cancer that were separately complexed with liposomes to form serum-stable RNA lipoplexes (RNA-LPX).
* The RNA molecules were immune-pharmacologically optimized for high stability, translational efficiency and presentation on major histocompatibility complex (MHC) class I and II molecules. The vaccine was intended for intravenous (IV) bolus injection.
* The RNA-LPX cancer vaccine induced 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 was associated with programmed death receptor-1 (PD-1) upregulation on these T cells. Thus, the cancer vaccine was expected to have a synergistic mechanism of action with anti-PD-1.
* The step-up dose titration approach allowed for optimal dose management on an individual basis and accounted for inter- and intra-individual variability of the immune system.
* 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 presented 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 Cemiplimab BNT112 in combination with cemiplimab 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
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) Cycle 1 (21 days) DLT criteria were defined as following: any treatment-emergent adverse events (TEAE) of Grade 5 intensity; hematological toxicities (Grade 3 and 4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 and 4 hemorrhage associated with thrombocytopenia of Grade greater than or equal to \[\>=\] 3, Grade 4 anemia); and non-hematological toxicities (Grade 4 cytokine release syndrome \[CRS\], Grade 3 CRS which has not improved to Grade 1 or resolved within 48 hours; any Grade \>=3 non-hematological TEAE at least possibly related which occurs during the first BNT112 cancer vaccine treatment cycle).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Related to Trial Procedure From Baseline up to 30 days after the last dose of BNT112 (for Part 1 and Part 2 Arms 1b and 3) or up to 90 days after the last dose of cemiplimab (for Part 2, Arm 1a and Arm 2) (up to 4 years and 1 month) TEAE: any adverse event (AE) with an onset date on or after the first administration of investigational medicinal product (IMP) or worsened after first administration of IMP. AEs with an onset date more than 30 days after last dose of BNT112 or 90 days after last dose of cemiplimab (for Part 2, Arm 1a and Arm 2) were only considered as TEAEs if assessed as related to IMP by the investigator. Serious adverse event (SAE): any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect or was another medically important condition. AEs were graded for severity using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0), where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; Grade 5: Death related to AE.
Part 2 Arm 1a: Objective Response Rate (ORR) From start of treatment up to 46 weeks ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) as per Prostate Cancer Working Group 3 (PCWG3) criteria as determined by the investigator. Participants not meeting the criteria for CR or PR, including those without any post-baseline tumor assessments, were considered as non-responders. CR was defined as the disappearance of all target lesions, with a reduction in short axis to \<10 mm in any pathological lymph nodes and no new lesions. PR was defined as 30% decrease in the sum of the longest diameter of target lesions.
Part 2 Arm 1b: Objective Response Rate (ORR) From start of treatment up to 104 weeks ORR was defined as the percentage of participants with a CR or PR as per PCWG3 criteria as determined by the investigator. Participants not meeting the criteria for CR or PR, including those without any post-baseline tumor assessments, were considered as non-responders. CR was defined as the disappearance of all target lesions, with a reduction in short axis to \<10 mm in any pathological lymph nodes and no new lesions. PR was defined as 30% decrease in the sum of the longest diameter of target lesions.
- Secondary Outcome Measures
Name Time Method Number of Participants Reporting Change From Baseline in Prostate-specific Antigen (PSA) Levels Day8 (Cycles1&2 only), Day1 Cycle 2 & Day 15 (Cycles1,2 & 8 only) (each cycle of 21-days), & EOT (30 days after last dose of BNT112 [Part 1 & Part 2 Arms 1b & 3] or 90 days after last dose of cemiplimab [Part 2, Arm 1a & Arm 2] [up to 4 years & 1 months]) Participants blood samples were tested for levels of PSA to track the progression of prostate cancer. PSA decline categories of No decline, 0 to 25%, \>25% to 50%, and \>50% compared to baseline during treatment according to PCWG3 (as reported by the investigator) are reported in this outcome measure. EOT in the timeframe below refers to End of treatment.
Number of Participants Reporting Change From Baseline in PSA Doubling Time (PSADT) Cycle 4 Day 1, Cycle 8 Day 1, Cycle 12 Day 1 (each cycle duration=21 days) Participants blood samples were tested for levels of PSA to track the progression of prostate cancer. PSADT was calculated using a linear regression model of the natural logarithm of PSA values and time. PSA doubling time compared to baseline during the treatment period for the following categories: 0 - 3 months; \>3 - 6 months; \>6 - 9 months; \>9 - 12 months; \>12 - 18 months; \>18 - 24 months; \>24 months and declining are reported in this outcome measure.
Number of Participants With PSA Decline of >=50% Day8 (Cycles1&2 only), Day1 Cycle 2 & Day 15 (Cycles1,2 & 8 only) (each cycle of 21-days), & EOT (30 days after last dose of BNT112 [Part 1 & Part 2 Arms 1b & 3] or 90 days after last dose of cemiplimab [Part 2, Arm 1a & Arm 2] [up to 4 years & 1 months]) Participants blood samples were tested for levels of PSA to track the progression of prostate cancer. Participants with PSA decline of \>=50% compared to baseline according to PCWG3 (as reported by the investigator) are reported in this outcome measure. EOT in the timeframe below refers to End of treatment.
Part 1: Objective Response Rate (ORR) From start of treatment up to 27 weeks ORR was defined as the percentage of participants with a CR or PR as per PCWG3 criteria as determined by the investigator. Participants not meeting the criteria for CR or PR, including those without any post-baseline tumor assessments, were considered as non-responders. CR was defined as the disappearance of all target lesions, with a reduction in short axis to \<10 mm in any pathological lymph nodes and no new lesions. PR was defined as 30% decrease in the sum of the longest diameter of target lesions.
Part 2: Arms 2 and 3: Number of Participants With Tumor Response Post-Treatment From start of treatment up to 25 weeks (Arm 2) and up to 26 weeks (Arm 3) The best overall response was defined as a single best response status at any tumor response assessment after first administration of IMP and prior to or at the start date of the first subsequent anti-cancer therapy. Overall response of progressive disease within 14 days after the start date of first subsequent anti-cancer therapy was considered. The following order of tumor response categories were used, where "Complete Response" is the best category: Complete Response (CR) - Partial Response (PR) - Stable Disease (SD) - Progressive Disease (PD) - Not Evaluable (NE) - Missing. CR: disappearance of all target lesions, with reduction in short axis to \<10 mm in any pathological lymph nodes and no new lesions. PR:30% decrease in the sum of the longest diameter of target lesions. PD: progression of target lesions (sum of diameter increase to nadir of \>=20% and by \>=5 mm), progression of existing non-target lesions, or appearance of 1 or more new lesions.SD: no evidence of PD, CR or PR.
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
ðŸ‡ðŸ‡ºNyÃregyháza, Hungary
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Magyar Honvédség Egészségügyi Központ (MH EK Honvédkórház)
ðŸ‡ðŸ‡ºBudapest, Hungary
Semmelweis Egyetem, Belgyógyászati Klinika
ðŸ‡ðŸ‡ºBudapest, Hungary
Onkológiai Klinika
ðŸ‡ðŸ‡ºDebrecen, Hungary
Szent Borbála Kórház
ðŸ‡ðŸ‡ºTatabánya, 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