Antibody CC-1 in Men With Biochemical Recurrence of Prostate Cancer

NCT05646550 | Recruiting Phase 1 DMC

• 3 other identifiers: ProSperA_CC-12022-002420-132024-511430-12-00
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer Recurrent

Outcome Measures

Primary Outcomes (2)

• Dose escalation part: To define the maximum tolerated dose (MTD) of CC-1 as 3 hours infusion

  Data Safety and Monitoring Board (DSMB) and Sponsor meeting about determination of the MTD for each cohort and the dose expansion phase

  during the procedure

• Dose expansion part: To define the recommended phase-II dose of CC-1

  Data Safety and Monitoring Board and Sponsor meeting about determination of the recommended phase II dose of CC-1 for potential phase II trials.

  up to 1 month after procedure

Secondary Outcomes (5)

• To evaluate safety and tolerability of CC-1

  during the procedure

• To assess efficacy in terms of Prostata-Specific-Antigen (PSA) response and no PSA progression after CC-1 treatment

  during the procedure and through study completion, an average of 6 months

• To assess clinical outcome in terms of progression-free survival, treatment-free survival, overall survival

  through study completion, an average of 6 months

• To assess CC-1 serum concentrations

  during the procedure prior to and after start of infusion on each treatment day in the first cycle (each cycle is 28 days).

• To assess quality of life

  through study completion, an average of 1 year

Other Outcomes (2)

• To identify predictive biomarkers of response and resistance

  during the procedure

• To evaluate pharmacokinetics and pharmacodynamics of CC-1 using Cytokine levels

  baseline and immediately after procedure

Study Arms (2)

Dose Escalation Part

EXPERIMENTAL

In the dose escalation part, up to 7 dose cohorts will be included depending on occurrence of dose-limiting toxicity (DLT). Each dose cohort has a predefined day 3 dose level (DL): cohort 1, 78µg; cohort 2, 110µg; cohort 3, 150µg; cohort 4, 210µg; cohort 5, 300µg; cohort 6, 400µg; cohort 7, 600µg. Each dose cohort will consist of at least three patients evaluable for DLT. Maximum tolerated dose (MTD) is defined on at least six patients

Drug: CC-1 Infusion

Dose Expansion Part

EXPERIMENTAL

CC-1 is administered as a 3-hour short-term intravenous infusion started at the MTD dose level identified in the dose escalation part of the study or based on the discretion of the sponsors delegate and DSMB recommendation supported by preliminary safety and efficacy data to constitute a modified MTD, e.g. to be one or more dose levels lower than the MTD determined. Patients can be treated simultaneously during the dose expansion phase. Patients must be hospitalized during step dosing, i.e. from day 1-4 (last dosing on day 3) of the first cycle. Thereafter inpatient treatment (overnight stay) depends on the discretion of the investigator, an outpatient treatment is preferred.

Drug: CC-1 Infusion

Interventions

CC-1 Infusion DRUG

Short term (3h) infusion of CC-1

Dose Escalation Part; Dose Expansion Part

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tuebingen

Tübingen, 72076, Germany

RECRUITING

Study Officials

• Walz, Prof. Dr.

  CCU Translational Immunology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Walz

CONTACT

+49(0)707129; kketi@med.uni-tuebingen.de

Jonas Heitmann, Dr.

CONTACT

+49(0)707129; jonas.heitmann@med.uni-tuebingen.de

Study Design

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

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: December 12, 2022
• Study Start: November 11, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)