Study With Bispecific Antibody Engaging T-cells, in Patients With Progressive Cancer Diseases With Positive PSCA Marker

NCT03927573 | Terminated Phase 1 DMC

• 1 other identifier: GEM3PSCA-01
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 5

Brief Summary

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug GEM3PSCA in patients with prostate stem cell antigen (PSCA) expressing cancer types which failed to respond to standard therapy.

Conditions

Non-small Cell Lung Cancer; Prostate Cancer; Renal Cancer; Transitional Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects.

  End of Treatment (EOT) +14 days (DLT period)

• Incidence and intensity of adverse events

  graded according to CTCAE V4.03

  End of Treatment (EOT) +14 days (DLT period)

• Incidence of Dose limiting toxicity (DLT)

  Dose Limiting Toxicity is defined as any event at least possibly related to investigational medicinal product (IMP)

  End of Treatment (EOT) +14 days (DLT period)

Secondary Outcomes (5)

• Recommended phase 2 dose (RP2D)

  From start of treatment until up to 14 days after last treatment cycle (2 initial cycles + max. 6 additional cycles per patient). Each cycle consists of 7 days treatment plus DLT evaluation period (14 days)

• Antitumor activity of GEM3PSCA according to RECIST1.1 (Response Evaluation Criteria in Solid Tumors)

  End of Treatment (EOT) +14 days (DLT period)

• Prostate specific antigen (PSA) response in patients with prostate cancer

  End of Treatment (EOT) +14 days (DLT period)

• Overall survival (OS)

  End of Treatment (EOT) + 14 days (DLT period)

• Influence on circulating tumor cells in patients with prostate cancer

  Day 8 / End of Treatment (EOT)

Study Arms (1)

GEM3PSCA

EXPERIMENTAL

Application of GEM3PSCA, a PSCA targeted bispecific antibody engaging T-cells

Drug: GEM3PSCA

Interventions

GEM3PSCA DRUG

Infusion of GEM3PSCA, administered intravenously, continuously over 7 days, 2 cycles

GEM3PSCA

Eligibility Criteria

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

You may qualify if:

• Male or female patients, ≥ 18 years of age
• Progressive PSCA positive cancer (urogenital tract (renal, transitional cell, prostate), non-small cell lung) refractory to standard treatments and with no other available standard or curative treatment
• Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Life expectancy of at least 2 months
• Platelets \> 50,000/µl
• Hemoglobin \> 9 g/dl
• Adequate renal and hepatic laboratory assessments
• Adequate pulmonary function with oxygen saturation (SpO2) ≥ 90 % and no structural pulmonary disease which might jeopardize patient safety according to judgement of the investigator
• Left ventricular ejection fraction (LVEF) of ≥ 45 %
• Existing port-system or central venous catheter resp. acceptance of implantation of a device
• A female of childbearing potential may be enrolled providing she has a negative pregnancy test at screening visit and is routinely using a highly effective method of birth control resulting in a low failure rate (e.g. hormonal contraception, intrauterine device, total sexual abstinence or sterilization) until 3 months from the last study drug administration. Male patients must also practice a highly effective method of birth Control
• Able to give written informed consent

You may not qualify if:

• Other malignancy requiring active therapy
• Non-measurable tumor disease
• Patients with active brain metastases (patients with brain metastases or residue after resection with stable size for 6 months in MRI not older than 8 weeks, after consultation with the sponsor, are not excluded from the trial)
• Use of chemotherapy and radiotherapy within 2 weeks prior to start of trial medication
• Use of checkpoint inhibitors (having a marketing authorization) within a washout of 5 x t1/2 (half-life); patients with experimental checkpoint inhibitors at all
• Other investigational drug within the past 4 weeks before start of trial medication
• Patients undergoing renal dialysis
• Pulmonary disease with clinical relevant hypoxia
• Evidence of active, non-infectious pneumonitis or history of interstitial lung disease
• Cardiac disease: i.e. heart failure NYHA (New York Heart Association) III or IV, unstable coronary artery disease
• Active central nervous disease (e.g. Parkinson, multiple sclerosis, seizures) and stroke within last 6 months
• Active gastrointestinal ulceration or bleeding within the last 6 months unless related to underlying malignant disease
• Renal outflow obstruction, macroscopic or significant microscopic hematuria
• Active infectious diseases considered by investigator to be incompatible with protocol
• Major surgery within 28 days

Sponsors & Collaborators

• AvenCell Europe GmbH: lead
• GCP-Service International Ltd. & Co. KG: collaborator

Study Sites (5)

Klinikum rechts der Isar der TU München

Munich, Bavaria, 81675, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Universitätsklinikum Marburg

Marburg, Hesse, 35043, Germany

Location

Universitätsklinikum Dresden

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Prostatic Neoplasms; Kidney Neoplasms; Carcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Ralf Bargou, Prof. Dr.

  Universitätsklinikum Würzburg, Interdisziplinäres Studienzentrum mit ECTU

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 25, 2019
• Study Start: April 15, 2019
• Primary Completion: June 28, 2023
• Study Completion: June 28, 2023
• Last Updated: July 10, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)