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Prostate CancerPhase 1/2PRO-MERITNCT04382898

PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy)

A Phase 1/2 study testing BNT112 and Cemiplimab in people with Prostate Cancer, run by BioNTech SE at 22 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
BNT112 and Cemiplimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
22 sitesin 4 countries
Study dates
19 Dec 2019to 23 Jan 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients were male and aged >=18 years.
  • Patients had histologically confirmed prostate adenocarcinoma.
  • Patients had 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 had histologically confirmed mCRPC and had 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 refused any of these therapies. These lines of therapy included 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 was luteinizing hormone-releasing hormone analogue (LHRHa), there was a plan to maintain effective LHRHa therapy for the duration of the trial.
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  • Patients had documented mCRPC progression within 6 months prior to screening (assuming no subsequent change in treatments), as determined by the investigator.
  • Patients agreed 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 had at least 1 of the following:
  • PSA >20 ng/mL or
  • Gleason Score >7 or
  • Localized stage >=cT2c, N0, M0 according to tumor, node, metastasis classification.
  • Patients who intend to have and were suitable for a radical prostatectomy.
  • Patients agreed 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 were patients with malignancies with a negligible risk of metastasis or death, that had 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 might be included.
  • Patients who had major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, or have not fully recovered from surgery, or had 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 had a known history of any of the following:
  • Human immunodeficiency virus (HIV) 1 or 2
  • Hepatitis B (carrier or active infection)
  • Hepatitis C (unless considered cured 5 years post curative anti-viral therapy)
  • Patients who have received or currently receive the following therapy/treatment:
  • 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.
  • 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.
  • 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.
  • Prior treatment with live-attenuated vaccines within 4 weeks before the first dose of IMP and during treatment with IMP.
  • 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.
  • 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) might be enrolled.
  • Concurrent use of herbal products that might 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.
  • Patients with a history of symptomatic metastatic brain or meningeal tumors might be included, if the end of definitive therapy was >3 months before the first dose of BNT112 and the patients had no clinical or radiological evidence of tumor growth.
  • Patients with brain metastases must not be undergoing acute or chronic corticosteroid therapy or steroid taper.
  • 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 received or currently receive the following anti-cancer therapy/agent:
  • Prior radiation therapy with curative intent within 14 days before the first dose of IMP. Note: Palliative radiotherapy is allowed.
  • 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.
  • 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 was longer) before the first dose of IMP.

Who cannot join

None listed.

Trial locations and contacts

22 sites in 4 countries.

22 sites in 4 countries

Germany6 sites

  • Universitätsklinikum Bonn

    Bonn, 53105

  • Klinikum der Johann Wolfgang Goethe-Universität

    Frankfurt, 60590

  • Universitätsklinikum Münster

    Münster, 48149

  • Studienpraxis Urologie

    Nürtingen, 72622

  • Urologische Klinik Planegg

    Planegg, 82152

  • Universitätsklinikum Tübingen

    Tübingen, 72076

Other trials in Germany

United Kingdom6 sites

  • Cancer Research UK Cambridge Centre

    Cambridge, CB2 0RE

  • Velindre Cancer Centre (VCC)

    Cardiff, CF14 2TL

  • University of Glasgow, Beatson WoS Cancer Centre

    Glasgow, G12 0YN

  • University College London Hospitals

    London, NW1 2PG

  • The Royal Marsden Hospital

    London, SW3 6JJ

  • University Hospital Southampton - Southampton General Hospital

    Southampton, SO16 6YD

Other trials in United Kingdom

United States5 sites

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • University of Miami Hospital & Clinics /Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • University of Pittsburgh Cancer Inst.

    Pittsburgh, Pennsylvania, 15215

  • Urology San Antonio P.A.

    San Antonio, Texas, 78229

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85724

Other trials in United States

Hungary5 sites

  • Magyar Honvédség Egészségügyi Központ (MH EK Honvédkórház)

    Budapest, 1062

  • Semmelweis Egyetem, Belgyógyászati Klinika

    Budapest, 1083

  • Onkológiai Klinika

    Debrecen, 4032

  • Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház

    Nyíregyháza, 4400

  • Szent Borbála Kórház

    Tatabánya, 2800

Other trials in Hungary

About this study

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

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.

Read the 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.
Conditions
Prostate Cancer
Being tested
BNT112, Cemiplimab
Keywords
Prostate cancer, PRO-MERIT, Cancer vaccine, W_pro1, BioNTech SE, RNA, mCRPC, LPC, Cemiplimab, BNT112
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BNT112Biological

    Intravenous bolus injection

  • CemiplimabDrug

    Intravenous infusion

Study groups in NCT04382898
Study groupRoleWhat they receive
Part 1 (mCRPC) - dose titrationExperimentalBNT112 monotherapy Enrollment into this arm is completed.
Receives: Biological: BNT112
Part 2 Arm 1A (mCRPC) - expansion cohortExperimentalBNT112 in combination with cemiplimab Enrollment into this arm is completed.
Receives: Biological: BNT112; Drug: Cemiplimab
Part 2 Arm 1B [1] (mCRPC) - expansion cohortExperimentalBNT112 monotherapy Enrollment into this arm is completed.
Receives: Biological: BNT112
Part 2 Arm 2 (LPC) - expansion cohortExperimentalBNT112 in combination with cemiplimab
Receives: Biological: BNT112; Drug: Cemiplimab
Part 2 Arm 3 (LPC) - expansion cohortExperimentalBNT112 monotherapy
Receives: Biological: BNT112
Part 2 Arm 1B [2] (mCRPC) - expansion cohortExperimentalFollowing progression after BNT112 monotherapy, patients in Arm 1b have the option to be treated with cemiplimab monotherapy Enrollment into this arm is completed.
Receives: Drug: Cemiplimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

    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).

    Measured: Cycle 1 (21 days)

  2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Related to Trial Procedure

    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.

    Measured: 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)

  3. Part 2 Arm 1a: Objective Response Rate (ORR)

    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.

    Measured: From start of treatment up to 46 weeks

  4. Part 2 Arm 1b: Objective Response Rate (ORR)

    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.

    Measured: From start of treatment up to 104 weeks

Secondary outcomes (5)

  1. Number of Participants Reporting Change From Baseline in Prostate-specific Antigen (PSA) Levels

    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.

    Measured: 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])

  2. Number of Participants Reporting Change From Baseline in PSA Doubling Time (PSADT)

    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.

    Measured: Cycle 4 Day 1, Cycle 8 Day 1, Cycle 12 Day 1 (each cycle duration=21 days)

  3. Number of Participants With PSA Decline of >=50%

    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.

    Measured: 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])

  4. Part 1: Objective Response Rate (ORR)

    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.

    Measured: From start of treatment up to 27 weeks

  5. Part 2: Arms 2 and 3: Number of Participants With Tumor Response Post-Treatment

    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.

    Measured: From start of treatment up to 25 weeks (Arm 2) and up to 26 weeks (Arm 3)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2020
  2. Study start19 Dec 2019
  3. Primary completion23 Jan 2024
  4. Study completion23 Jan 2024

Why it stopped: Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04382898
Sponsor's protocol ID
RN5609C00
Other IDs
2018-004321-86, 2018
Acronym
PRO-MERIT
Status last verified
Mar 2025
First submitted
21 Apr 2020
Last updated
20 Mar 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BNT112 and Cemiplimab in people with Prostate Cancer, run by BioNTech SE at 22 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Germany, United Kingdom, United States, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (21 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04382898.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.

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