| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Male adults with prostate cancer, both mCRPC (Arms 1A & 1B) and LPC (ARms 2&3) patients, will be treated with BNT112 alone or in combination with cemiplimab. LPC patients will also receive neo-adjuvant goserelin acetate therapy addition to BNT112 with or without Cemiplimab. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Prostate cancer (PC) spread beyond the prostate gland and is resistant to hormone therapy and newly diagnosed high-risk localised prostate cancer (LPC) which has not spread beyond the gland. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10036909 |
| E.1.2 | Term | Prostate cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10007113 |
| E.1.2 | Term | Cancer of prostate |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
PRIMARY OBJECTIVE
For Part 1 and Part 2: Assess safety and tolerability profile of BNT112 monotherapy or in combination with cemiplimab
For Part 2 Arms 1A and 1B: Evaluate preliminary antitumor activity of BNT112 monotherapy and in combination with cemiplimab in patients with metastatic castration-resistant prostate cancer (mCRPC) based on ORR
|
|
| E.2.2 | Secondary objectives of the trial |
Evaluate anti-tumor activity based on levels of prostate specific antigen (PSA)
(Part 1) Evaluate preliminary anti-tumor activity of BNT112 monotherapy in patients with mCRPC based on ORR.
Evaluate preliminary anti-tumor activity of BNT112 monotherapy or in combination with cemiplimab in patients with newly diagnosed localised prostate cancer (LPC) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Main INCLUSION criteria for ALL patients
• Patient must be male and aged ≥ 18 years
• Patient must have histologically confirmed prostate adenocarcinoma.
• Patients or their legally authorized representative (if applicable) must sign an informed consent form (ICF) indicating that they understand the purpose of the procedures required for the trial and are willing to participate.
• Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
• Patient must have adequate organ and bone marrow function.
• Patients who are sexually active with a woman of childbearing potential must agree to use a condom with spermicidal foam/gel/film/cream/suppository in addition to at least one form of highly effective contraception used by the patient or their partner (for details, see Section 10.4) during the trial starting after signing the ICF and for 90 days after receiving the last dose of BNT112 OR for 6 months after receiving the last dose of cemiplimab.
• Patients should not donate sperm during the trial starting after signing the ICF and for 90 days after receiving the last dose of BNT112 OR for 6 months after receiving the last dose of cemiplimab.
Main SPECIFIC 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 or have refused 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).
• Patients must have documented mCRPC progression within 6 months prior to screening (assuming no subsequent change in treatments), as determined by the investigator, by means of 1 or more of the following:
- PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be > 2 ng/mL.
- Two rises out of 3 PSA sequential tests separated by at least 1 week also satisfies the criteria for baseline progression providing a new nadir is not established (i.e., upward trend)
- Radiographic disease progression in soft tissue based on modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) with or without PSA progression.
- Radiographic disease progression in soft tissue based on modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) with or without PSA progression.
- Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression.
• Patients must have adequate liver function
• Patients must agree to provide an archival pre-treatment formalin-fixed, paraffin-embedded tumor sample if available.
Main SPECIFIC 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)24 and in line with the U.S. National Comprehensive Cancer Network (NCCN 2020), patients must have at least one of the following:
- PSA > 20 ng/mL or
- Gleason Score > 7 or
- 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 have adequate liver function
• Patients must agree to provide tumor sample(s) from pre-treatment diagnostic biopsy and planned post-treatment surgery.
• Patients must be eligible for up to 6 months of ADT treatment before prostatectomy. |
|
| E.4 | Principal exclusion criteria |
Main exclusion criteria for ALL patients
• Patient has uncontrolled intercurrent illness, including but not limited to:
- Ongoing or active infection which requires systemic treatment with antibiotics or corticoid therapy within 14 days before the first dose of IMP.
- Symptomatic congestive heart failure (NYHA Grade III or IV), myocardial infarction within 3 months before screening, unstable angina pectoris, or cardiac arrhythmia.
- Known recent history (in the past 5 years) or presence of significant pulmonary conditions.
- Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, despite optimal medical management.
- Known primary immunodeficiencies, either cellular or combined T- and B-cell immunodeficiencies.
- Ongoing or recent evidence (within the past year) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may suggest risk for immune-related AEs.
- Non-healing wound, skin ulcer (of any grade), or bone fracture.
- Patients with prior allogeneic stem cell or solid organ transplantation.
- Patients with the risk factors for bowel perforation.
- Patients with uncontrolled Type 1 diabetes mellitus.
- Patients with uncontrolled adrenal insufficiency.
- Any other disease, metabolic dysfunction, physical examination finding and/or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or may render the patient at high-risk for treatment of complications.
• Patients with a known history or current malignancy other than the inclusion diagnosis.
• Patients who have had a splenectomy.
• Patients who have had a major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, or have not have 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 with a known history of any of the following:
a. HIV 1 or 2
b. Hepatitis B
c. Hepatitis C
• Patients with a known allergy, hypersensitivity, or intolerance to BNT112 or its excipients (all patients in Parts 1 and 2), cemiplimab or its excipients (patients in Part 2 Arm 1A, Arm 1B switch-over patients, and Arm 2 only), or to ADT (e.g., goserelin)or its excipients (patients in Part 2 Arms 2 and 3 only).
• Patients with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments.
• In situations where trial patients are not legally competent to provide consent (e.g. mentally incapacitated), these patients are not allowed to enter the trial.
Prior/Concomitant Therapy
•Patients who have received or currently receive the following therapy/treatment:
a. Chronic systemic immunosuppressive corticosteroid treatment (prednisone >5 mg daily PO or IV, or equivalent) during the trial.
b. Prior treatment with other immune modulating agents under conditions set in the Protocol.
c. Prior treatment with live attenuated vaccines within 4 weeks before the first dose of IMP and during treatment with IMP.
d. Prior treatment with an investigational drug within 4 weeks or 5 half-lives of the agent (whichever is longer) before the planned first dose of IMP.
e. Therapeutic PO or IV antibiotics within 14 days prior to enrollment.
f. Concurrent use of herbal products that may decrease PSA levels
• Patients who have previously been enrolled in this trial.
• Patients affiliated with the investigational site
Specific exclusion criteria for mCRPC patients (Part 1 and Part 2 Arm 1A and 1B)
• Patients with toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade ≤1 according to 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 who have received or currently receive the following anti-cancer therapy/agent:
a. Prior radiation therapy with curative intent within 14 days before the first dose of IMP.
b. 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.
c. Prior treatment with anti-cancer immunomodulating agents, such as blockers of PD-1, PD-L1, 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
Specific exclusion criteria for LPC patients (Part 2 Arms 2 and 3)
• Patients who are expected to be unable to undergo an mpMRI or MRI. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
For Part 1 and Part 2:
• Occurrence of dose-limiting toxicities (DLTs)
• Occurrence of TEAEs reported by relationship, grade, and seriousness according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
For Part 2 Arms 1A and 1B:
• ORR, defined as the number of patients with a complete response (CR) or partial response (PR) per Prostate Cancer Working Group 3 (PCWG3) as determined by the investigator as best objective response divided by the number of patients in the analysis set. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
• DLTs of BNT112 will be continuously monitored during the first treatment cycle (21 days [28 days]) in the Dose Titration Part of Part 1 Arm 1 (mCRPC), and
• AEs will be continuously monitored from the moment that patient signs the general informed consent form for trial participation up to the end of the safety follow-up period (30 days for Arm 1A&1B + Arm 3, 90 days for Arm 2). |
|
| E.5.2 | Secondary end point(s) |
• PSA decline of 0 to 25%, >25% to 50%, and >50% compared to baseline.
• PSA doubling time (PSADT) post-treatment on C4D1 and D1 of every fourth subsequent cycle (e.g., C8D1, C12D1, etc.) in Part 1 and Part 2 Arm 1A and 1B, or on C4D1, C8D1, and EoT in Part 2 Arms 2 and 3 compared to baseline.
• PSA decline of ≥50% (according to the PCWG3).
• ORR, defined as the number of patients with a CR or PR per PCWG329 as determined by the investigator as best objective response divided by the number of patients in the analysis set.
• Tumor response post-treatment compared to baseline. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| See description of endpoints |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United Kingdom |
| United States |
| Germany |
| Hungary |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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