Overview

This trial is a phase I open-label, single center study designed to evaluate the safety, tolerability and preliminary efficacy of the bispecific prostate specific membrane antigen (PSMA) and cluster of differentiation protein 3 (CD3) antibody CC-1 in men with biochemical recurrence (BCR) of prostate cancer (PC). The PSMA binder in CC-1 reacts with tumor cells and also binds to tumor vessels, thereby allowing for a dual mode of anti-cancer action. CC-1 was developed in a novel format, which not only prolongs serum half-life, but most importantly reduces off-target T-cell activation with accordingly reduced side effects. The study entails a part I (dose escalation part) to identify the maximally tolerated dose of CC-1, which then will be further evaluated in part II of the study (dose expansion part). After application of two low doses as safety steps in the first cycle, CC-1 will be applied twice weekly for three consecutive weeks within 4 week cycles as a short-term intravenous infusion (3 hours). The planned trial ultimately shall define the recommended phase II dose (RP2D) of CC-1 in the disease setting of BCR of PC.

Eligibility

Inclusion Criteria:

• Written informed consent
• Patient is able to understand and comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
• Men aged 18 and above
• Earlier histologic diagnosis of prostatic adenocarcinoma
• Low risk of rapid disease progression, defined as:
  • PSA-detection Time (DT) > 1 year AND pathological International Society of Urological Pathology (ISUP) grade < 4 for men with prior radical prostatectomy or Interval to biochemical recurrence > 18 months and biopsy ISUP grade < 4 for men with prior radiation therapy
• Biochemical recurrence (BCR) in compliance with the following 3 conditions:
  • after having finished last definitive treatment
  • PSA ≥0.2 ng/mL or PSA > nadir + 2 ng/mL (after definitive RT), with two increasing PSA values prior to study treatment
  • no distant metastasis upon PSMA- positron emission tomography (PET) imaging
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
• Male patients with partners of child-bearing potential, who are sexually active, must agree to the use of one highly effective form of contraception and one barrier method. This should be started from the signing of the informed consent and continue throughout period of taking study treatment and for 4 months after the last dose of study drug
• Adequate bone marrow, renal, and hepatic function defined by laboratory tests within 21 days prior to study treatment:
  • Hemoglobin ≥ 9 g/dl (Transfusion of packed red blood cells prior to enrolment allowed)
  • Neutrophil count ≥ 1,500/mm3
  • Platelet count ≥ 100,000/µl
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
  • gamma-glutamyl-transferase (γ-GT) ≤ 2.5 x ULN
  • prothrombin time (PT) - international normalised ratio (INR) / partial thromboplastin time (PTT) ≤ 1.5 x ULN
  • Creatine kinase ≤ 2.5 x ULN
  • Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 ml/min

Exclusion Criteria:

• PSA >5 ng/ml.
• For men with prior radical prostatectomy:
  • PSA-DT < 1 year or
  • pathological ISUP grade 4-5
• For men with prior radiation therapy:
  • Interval to biochemical recurrence < 18 months or
  • biopsy ISUP grade 4-5
• Other malignancy within the last 2 years except: adequately treated non-melanoma skin

  cancer and low-grade non-muscle invasive papillary bladder cancer.

• Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy
• Patients who are receiving androgen-deprivation therapy.
• Patients who have received prior Androgen Deprivation Therapy (ADT) are not eligible with the exception of those that received ADT ≤ 36 months in duration and ≥9 months before enrolment and administered only in the neoadjuvant/adjuvant setting.
• Castrate level of serum testosterone <50 ng/dL at screening.
• History of HIV infection
• Viral active or chronic hepatitis (HBV or HCV)
• Ongoing autoimmune disease
• Current relevant central nervous system pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)
• Therapeutic anticoagulation
• Non-controlled hypertension, defined as mean blood pressure values in 24-hours blood pressure measurement of >130 mmHg or >90 mmHg for systolic or diastolic, respectively
• Heart failure defined as New York Heart Association (NYHA) III/IV
• Severe obstructive or restrictive ventilation disorder
• Known intolerance to CC-1 or other immunoglobulin drug products as well as hypersensitivity to any of the excipients present in CC-1