Clinical Trials /

PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy)

NCT04382898

Description:

Open-label, multicenter, dose titration and four-arm expansion trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of W_pro1 cancer vaccine (W_pro1) 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).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: RN5609C00
  • SECONDARY ID: 2018-004321-86
  • NCT ID: NCT04382898

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
W_pro1Part 1 (mCRPC) - dose titration
CemiplimabPart 2 Arm 1A (mCRPC) - expansion cohort

Purpose

Open-label, multicenter, dose titration and four-arm expansion trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of W_pro1 cancer vaccine (W_pro1) 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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1 (mCRPC) - dose titrationExperimentalW_pro1 monotherapy
  • W_pro1
Part 2 Arm 1A (mCRPC) - expansion cohortExperimentalW_pro1 in combination with cemiplimab
  • W_pro1
  • Cemiplimab
Part 2 Arm 1B (mCRPC) - expansion cohortExperimentalW_pro1 monotherapy
  • W_pro1
Part 2 Arm 2 (LPC) - expansion cohortExperimentalW_pro1 in combination with cemiplimab
  • W_pro1
  • Cemiplimab
Part 2 Arm 3 (LPC) - expansion cohortExperimentalW_pro1 monotherapy
  • W_pro1

Eligibility Criteria

        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 (ECOG PS)
             score of 0 or 1.

        Specific key inclusion criteria for mCRPC patients (Part 1 and Part 2 Arms 1A and 1B):

          -  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 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 (Part 2 Arms 2 and 3):

          -  Treatment-naïve patients with high-risk LPC (i.e., 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 ≥cT2c, N0, M0 according to tumor, node, metastasis (TNM)
                  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:

        Medical conditions

          -  Patients with uncontrolled intercurrent illness.

          -  Patients with a known history or current malignancy other than the inclusion
             diagnosis. Note: Exceptions are patients with malignancies with a negligible risk of
             metastasis or death, that have 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 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 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.

               3. 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.

               4. 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.

               5. 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.

               6. 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.

               7. Concurrent use of herbal products that may decrease PSA levels (e.g., saw
                  palmetto).

        Specific key exclusion criteria for mCRPC Patients (Part 1 and Part 2 Arms 1A and 1B):

        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.

               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 (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 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 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.

               3. 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 is longer) before the first dose of IMP.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of dose limiting toxicities (DLTs)
Time Frame:up to 24 months
Safety Issue:
Description: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

Measure:Occurrence of de novo induction or increase of W_pro1 antigen-specific T cells in peripheral blood compared to baseline
Time Frame:up to 24 months
Safety Issue:
Description:
Measure:Change in prostate-specific antigen (PSA) levels
Time Frame:up to 24 months
Safety Issue:
Description:PSA decline of 0 to 25%, >25% to 50%, and >50% compared to baseline, as well as PSA decline ≥ 50% according to PCWG3.
Measure:Change in PSA doubling time (PSADT)
Time Frame:up to 24 months
Safety Issue:
Description:PSADT during treatment and end of treatment (EoT) compared to baseline.
Measure:Change in prostatic acid phosphatase (PAP) levels
Time Frame:up to 24 months
Safety Issue:
Description:PAP levels during treatment and at EoT compared to baseline.
Measure:ORR - Part 1
Time Frame:up to 24 months
Safety Issue:
Description:ORR, defined as the number of patients with a CR or PR per PCWG3.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BioNTech SE

Trial Keywords

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

Last Updated

January 14, 2021