The Bispecific PSMAxCD3 Antibody CC-1 in Patients with Castration Resistant Prostate Carcinoma

NCT04104607 | Recruiting Phase 1 DMC

• 2 other identifiers: DKTK_PMO_16052019-000238-20
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 2

Brief Summary

This trial is a first in human (FIH) study in patients with castration resistant metastatic prostate cancer (CRPC) after failure of third-line therapy aiming to evaluate safety and efficacy of CC-1, a bispecific antibody (bsAb) with PSMAxCD3 specificity developed within DKTK. CC-1 binds to human prostate-specific membrane antigen (PSMA) on prostate cancer cells as well as to tumor vessels of CRPC, 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 expected fewer side effects. Together with preemptive IL-6 receptor (IL-6R) blockade using tocilizumab, this allows for application of effective bsAb doses with expected high anticancer activity. The study comprises two phases. The first phase is a doseescalation phase with concomitant prophylactic application of tocilizumab to evaluate the maximally tolerated dose (MTD) of CC-1. This is followed by a dose-expansion phase (also with prophylactic IL-6R blockade using tocilizumab), as this approach has been shown to be efficient and beneficial for patients. A translational research program comprising, among others, analysis of CC-1 half-life and the induced immune response as well as molecular profiling in liquid biopsies will serve to better define the mode of action of CC-1 and to identify biomarkers for further clinical development.

Conditions

Castration-Resistant Prostatic Cancer

Keywords

PSMA; Resistant Prostate Cancer; PSMAxCD3; CC-1

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of adverse events (AEs) (CTCAE V5.0) over 21 days (i.e. until end of first treatment cycle (day 28))

  Grade 1 No interruption- No dose adjustment Grade 2 Interrupt until Grade 0/1- No dose adjustment Any Grade ≥ 3 Interrupt until Grade 0/1 Permanently stop, except that no DLT is caused; if the latter and if AE is resolved to Grade 0/1, resume with dose reduction by two dose levels

  Each cycle is 28 days; Safety Assessment on day 1-9,15,22,28

Secondary Outcomes (7)

• Immunogenicity:

  at day 90 of the last cycle of a given patient

• Cytokine induction

  baseline and at day 1-9, day 15 and day 21 in the first cycle.

• Measurment of the CC-1 blood serum concentration

  At Day1-7, 15 and 21 in the first cycle

• Anti-tumor activity

  day 8, 15 and d21 of each cycle, and at day 90 after last cycle of given patient

• Anti-tumor activity

  at day 90 and thereafter for 6 months every 3 months after last cycle of given patient

Study Arms (1)

CC-1 therapy

EXPERIMENTAL

Infusion of CC-1 over 24 hours for 7 days with possible intra-patient dose-escalation. In case of clinical benefit, additional cycles with a total of up to six are possible.

Drug: CC-1, PSMAxCD3

Interventions

CC-1, PSMAxCD3 DRUG

Infusion of CC-1 over 24 hours for 7 days with possible intra-patient dose-escalation

CC-1 therapy

Eligibility Criteria

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

You may qualify if:

• Existence of a 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
• CRPC after third line therapy
• Life expectance of \> 3 months
• At least one measurable lesion that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessment
• Eastern Cooperative Oncology Group Performance (ECOG) Status ≤ 2
• Patient aged ≥ 18, no upper age limit
• Male patients with partners of child-bearing potential, who are sexually active, must agree to the use of two highly effective forms of contraception. This should be started from the signing of the informed consent and continue throughout period of taking study treatment for 3 months after last dose of study drug.
• Adequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment:
• Hemoglobin ≥ 10 g/dl
• Neutrophil count ≥ 1,500/mm3
• Platelet count ≥ 100,000/μl
• Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• ALT and AST ≤ 2.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN

You may not qualify if:

• Patients fulfilling any of the following criteria cannot be enrolled in the trial:
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer
• Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy
• Persistent toxicity (≥Grade 2 according to Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) caused by previous cancer therapy, excluding alopecia and neurotoxicity (≤ 2 grade)
• Clinical signs of active infection (\>Grade 2 according to CTCAE version 5.0)
• History of HIV infection
• Immunocompromised patients
• Active or chronic viral hepatitis (HBV or HCV)
• History of autoimmune disease
• History of relevant CNS pathology or current relevant CNS 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) Epilepsy requiring pharmacologic treatment
• Therapeutic anticoagulation therapy
• Major surgery within 4 weeks of starting study treatment. Patients must have recovered from any effects of major surgery.
• Patients receiving any systemic chemotherapy or radiotherapy within 2 weeks prior to study treatment or a longer period depending on the defined characteristics of the agents used
• Heart failure NYHA III/IV
• Severe obstructive or restrictive ventilation disorder

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• German Cancer Research Center: collaborator

Study Sites (2)

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

University hospital Heidelberg

Heidelberg, BadenWuerttemberg, 69120, Germany

NOT YET RECRUITING

Related Publications (2)

• Lutz MS, Klimovich B, Maurer S, Heitmann JS, Marklin M, Zekri L, Jung G, Salih HR, Hinterleitner C. Platelets subvert antitumor efficacy of T cell-recruiting bispecific antibodies. J Immunother Cancer. 2022 Feb;10(2):e003655. doi: 10.1136/jitc-2021-003655.

  PMID: 35110356 DERIVED

• Heitmann JS, Walz JS, Pflugler M, Kauer J, Schlenk RF, Jung G, Salih HR. Protocol of a prospective, multicentre phase I study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration-resistant prostate carcinoma. BMJ Open. 2020 Oct 16;10(10):e039639. doi: 10.1136/bmjopen-2020-039639.

  PMID: 33067297 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Condition Hierarchy (Ancestors)

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

Study Officials

• Helmut R Salih, Prof.

  KKE Translational Immunology, University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helmut R Salih, Prof.

CONTACT

+49 (0)7071 29-83275; helmut.salih@med.uni-tuebingen.de

Juliane Walz, PD Dr. med.

CONTACT

+49 (0)7071 29-83275; juliane.walz@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, multicenter dose escalation and dose expansion phase I trial, designed to gain evidence of maximally tolerated and recommended phase-II dose of CC-1 in adult patients with CRPC.

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: September 26, 2019
• Study Start: November 15, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: IPD will be available starting 9 months and ending 36 months after publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. Data may only be used for meta-analysis. Proposals may be submitted up to 36 months following article publication to the corresponding investigator via e-mail.

Locations

DE (2)