PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy)

NCT04382898 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: RN5609C002018-004321-86
• Study Type: interventional
• Target: 75
• Locations: 4 countries
• Sites: 22

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.

Conditions

Prostate Cancer

Keywords

Prostate cancer; PRO-MERIT; Cancer vaccine; W_pro1; BioNTech SE; RNA; mCRPC; LPC; Cemiplimab; BNT112

Outcome Measures

Primary Outcomes (4)

• 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).

  Cycle 1 (21 days)

• 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.

  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)

• 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.

  From start of treatment up to 46 weeks

• 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.

  From start of treatment up to 104 weeks

Secondary Outcomes (5)

• 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])

• 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)

• 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])

• Part 1: Objective Response Rate (ORR)

  From start of treatment up to 27 weeks

• 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)

Study Arms (6)

Part 1 (mCRPC) - dose titration

EXPERIMENTAL

BNT112 monotherapy Enrollment into this arm is completed.

Biological: BNT112

Part 2 Arm 1A (mCRPC) - expansion cohort

EXPERIMENTAL

BNT112 in combination with cemiplimab Enrollment into this arm is completed.

Biological: BNT112; Drug: Cemiplimab

Part 2 Arm 1B [1] (mCRPC) - expansion cohort

EXPERIMENTAL

BNT112 monotherapy Enrollment into this arm is completed.

Biological: BNT112

Part 2 Arm 2 (LPC) - expansion cohort

EXPERIMENTAL

BNT112 in combination with cemiplimab

Biological: BNT112; Drug: Cemiplimab

Part 2 Arm 3 (LPC) - expansion cohort

EXPERIMENTAL

BNT112 monotherapy

Biological: BNT112

Part 2 Arm 1B [2] (mCRPC) - expansion cohort

EXPERIMENTAL

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

Interventions

BNT112 BIOLOGICAL

Intravenous bolus injection

Part 1 (mCRPC) - dose titration; Part 2 Arm 1A (mCRPC) - expansion cohort; Part 2 Arm 1B [1] (mCRPC) - expansion cohort; Part 2 Arm 2 (LPC) - expansion cohort; Part 2 Arm 3 (LPC) - expansion cohort

Cemiplimab DRUG

Intravenous infusion

Part 2 Arm 1A (mCRPC) - expansion cohort; Part 2 Arm 1B [2] (mCRPC) - expansion cohort; Part 2 Arm 2 (LPC) - expansion cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• Medical conditions
• Patients with uncontrolled intercurrent illness.
• 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).

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (22)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

University of Miami Hospital & Clinics /Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

University of Pittsburgh Cancer Inst.

Pittsburgh, Pennsylvania, 15215, United States

Location

Urology San Antonio P.A.

San Antonio, Texas, 78229, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universität

Frankfurt, 60590, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Studienpraxis Urologie

Nürtingen, 72622, Germany

Location

Urologische Klinik Planegg

Planegg, 82152, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Magyar Honvédség Egészségügyi Központ (MH EK Honvédkórház)

Budapest, 1062, Hungary

Location

Semmelweis Egyetem, Belgyógyászati Klinika

Budapest, 1083, Hungary

Location

Onkológiai Klinika

Debrecen, 4032, Hungary

Location

Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház

Nyíregyháza, 4400, Hungary

Location

Szent Borbála Kórház

Tatabánya, 2800, Hungary

Location

Cancer Research UK Cambridge Centre

Cambridge, CB2 0RE, United Kingdom

Location

Velindre Cancer Centre (VCC)

Cardiff, CF14 2TL, United Kingdom

Location

University of Glasgow, Beatson WoS Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

University College London Hospitals

London, NW1 2PG, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

University Hospital Southampton - Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

+49 6131 9084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: May 11, 2020
• Study Start: December 19, 2019
• Primary Completion: January 23, 2024
• Study Completion: January 23, 2024
• Last Updated: March 20, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6); DE (6); HU (5); US (5)