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出境医 / 临床实验 / Study With Bispecific Antibody Engaging T-cells, in Patients With Progressive Cancer Diseases With Positive PSCA Marker

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

Study Description
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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Breast Cancer Pancreatic Cancer Prostate Cancer Renal Cancer Transitional Cell Carcinoma Drug: GEM3PSCA Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Dose-escalating, Phase I Trial With GEM3PSCA, a PSCA Targeted Bispecific Antibody Engaging T-cells, in Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSCA Marker
Actual Study Start Date : April 15, 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : December 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: GEM3PSCA
Application of GEM3PSCA, a PSCA targeted bispecific antibody engaging T-cells
 Drug: GEM3PSCA
Infusion of GEM3PSCA, administered intravenously, continuously over 7 days, 2 cycles
Outcome Measures
Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects.

  2. Incidence and intensity of adverse events [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    graded according to CTCAE V4.03

  3. Incidence of Dose limiting toxicity (DLT) [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    Dose Limiting Toxicity is defined as any event at least possibly related to investigational medicinal product (IMP)


Secondary Outcome Measures :
  1. Recommended phase 2 dose (RP2D) [ Time Frame: 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) ]
    The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.

  2. Antitumor activity of GEM3PSCA according to RECIST1.1 (Response Evaluation Criteria in Solid Tumors) [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    response rates

  3. Prostate specific antigen (PSA) response in patients with prostate cancer [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
  4. Overall survival (OS) [ Time Frame: End of Treatment (EOT) + 14 days (DLT period) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients, ≥ 18 years of age
  2. PSCA positive cancer (i.e. urogenital tract (renal, transitional cell, prostate), non-small cell lung, breast and pancreatic cancer) refractory to standard treatments and with no other available standard or curative treatment
  3. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  5. Life expectancy of at least 2 months
  6. Platelets > 50,000/µl
  7. Hemoglobin > 9 g/dl
  8. Adequate renal and hepatic laboratory assessments
  9. Adequate pulmonary function with oxygen saturation (SpO2) > 89 % and no structural pulmonary disease which might jeopardize patient safety according to judgement of the investigator
  10. Left ventricular ejection fraction (LVEF) of ≥ 45 %
  11. Existing port-system or central venous catheter resp. acceptance of implantation of a device
  12. 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
  13. Able to give written informed consent

Exclusion Criteria:

  1. Other malignancy requiring active therapy
  2. Non-measurable tumor disease
  3. Patients with brain metastases
  4. Use of chemotherapy and radiotherapy within 2 weeks prior to start of trial medication
  5. 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
  6. Other investigational drug within the past 4 weeks before start of trial medication
  7. Patients undergoing renal dialysis
  8. Pulmonary disease with clinical relevant hypoxia
  9. Evidence of active, non-infectious pneumonitis or history of interstitial lung disease
  10. Cardiac disease: i.e. heart failure NYHA (New York Heart Association) III or IV, unstable coronary artery disease
  11. Active central nervous disease (e.g. Parkinson, multiple sclerosis, seizures) and stroke within last 6 months
  12. Active gastrointestinal ulceration or bleeding within the last 6 months unless related to underlying malignant disease
  13. Renal outflow obstruction, macroscopic or significant microscopic hematuria
  14. Active infectious diseases considered by investigator to be incompatible with protocol
  15. Major surgery within 28 days
  16. Autoimmune diseases requiring steroids at a dose above 10 mg prednisolone equivalent or other immunosuppressants
  17. Pregnant or breastfeeding women
  18. Psychiatric disorders, drug and/or alcohol abuse
  19. Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
  20. Known hypersensitivity to GEM3PSCA excipients
  21. Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
  22. Incapability of understanding purpose and possible consequences of the trial
  23. Patients who should not be included according to the opinion of the investigator
Contacts and Locations

Contacts
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Contact: Susann Helas, Dr. +49 351 4466 4500 ext 0 gem3psca-01@gemoab.com
Contact: Martina Raupach

Locations
Layout table for location information
Germany
Klinikum rechts der Isar der TU München Recruiting
Munich, Bayern, Germany, 81675
Contact: Sylvie Lorenzen, Prof. Dr.         
Principal Investigator: Sylvie Lorenzen, Prof. Dr.         
Universitätsklinikum Würzburg Recruiting
Würzburg, Bayern, Germany, 97080
Contact: Mariele Goebeler, Dr.         
Principal Investigator: Ralf Bargou, Prof. Dr.         
Universitätsklinikum Marburg Recruiting
Marburg, Hessen, Germany, 35043
Contact: Stephan Metzelder, Dr.         
Principal Investigator: Stephan Metzelder, PD Dr.         
Universitätsklinikum Dresden Recruiting
Dresden, Sachsen, Germany, 01307
Contact: Martin Wermke, Dr.         
Principal Investigator: Martin Wermke, Dr.         
Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Principal Investigator: Gudhild von Amsberg, Prof. Dr.         
Sponsors and Collaborators
GEMoaB Monoclonals GmbH
GCP-Service International Ltd. & Co. KG
Investigators
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Principal Investigator: Ralf Bargou, Prof. Dr. Universitätsklinikum Würzburg, CCC Mainfranken
Tracking Information
First Submitted Date  ICMJE April 16, 2019
First Posted Date  ICMJE April 25, 2019
Last Update Posted Date April 20, 2021
Actual Study Start Date  ICMJE April 15, 2019
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • Maximum tolerated dose (MTD) [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects.
  • Incidence and intensity of adverse events [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    graded according to CTCAE V4.03
  • Incidence of Dose limiting toxicity (DLT) [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    Dose Limiting Toxicity is defined as any event at least possibly related to investigational medicinal product (IMP)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • Recommended phase 2 dose (RP2D) [ Time Frame: 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) ]
    The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
  • Antitumor activity of GEM3PSCA according to RECIST1.1 (Response Evaluation Criteria in Solid Tumors) [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
    response rates
  • Prostate specific antigen (PSA) response in patients with prostate cancer [ Time Frame: End of Treatment (EOT) +14 days (DLT period) ]
  • Overall survival (OS) [ Time Frame: End of Treatment (EOT) + 14 days (DLT period) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study With Bispecific Antibody Engaging T-cells, in Patients With Progressive Cancer Diseases With Positive PSCA Marker
Official Title  ICMJE A Multicenter, Open-label, Dose-escalating, Phase I Trial With GEM3PSCA, a PSCA Targeted Bispecific Antibody Engaging T-cells, in Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSCA Marker
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-small Cell Lung Cancer
  • Breast Cancer
  • Pancreatic Cancer
  • Prostate Cancer
  • Renal Cancer
  • Transitional Cell Carcinoma
Intervention  ICMJE Drug: GEM3PSCA
Infusion of GEM3PSCA, administered intravenously, continuously over 7 days, 2 cycles
Study Arms  ICMJE Experimental: GEM3PSCA
Application of GEM3PSCA, a PSCA targeted bispecific antibody engaging T-cells
Intervention: Drug: GEM3PSCA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 24, 2019) 		24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female patients, ≥ 18 years of age
  2. PSCA positive cancer (i.e. urogenital tract (renal, transitional cell, prostate), non-small cell lung, breast and pancreatic cancer) refractory to standard treatments and with no other available standard or curative treatment
  3. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  5. Life expectancy of at least 2 months
  6. Platelets > 50,000/µl
  7. Hemoglobin > 9 g/dl
  8. Adequate renal and hepatic laboratory assessments
  9. Adequate pulmonary function with oxygen saturation (SpO2) > 89 % and no structural pulmonary disease which might jeopardize patient safety according to judgement of the investigator
  10. Left ventricular ejection fraction (LVEF) of ≥ 45 %
  11. Existing port-system or central venous catheter resp. acceptance of implantation of a device
  12. 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
  13. Able to give written informed consent

Exclusion Criteria:

  1. Other malignancy requiring active therapy
  2. Non-measurable tumor disease
  3. Patients with brain metastases
  4. Use of chemotherapy and radiotherapy within 2 weeks prior to start of trial medication
  5. 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
  6. Other investigational drug within the past 4 weeks before start of trial medication
  7. Patients undergoing renal dialysis
  8. Pulmonary disease with clinical relevant hypoxia
  9. Evidence of active, non-infectious pneumonitis or history of interstitial lung disease
  10. Cardiac disease: i.e. heart failure NYHA (New York Heart Association) III or IV, unstable coronary artery disease
  11. Active central nervous disease (e.g. Parkinson, multiple sclerosis, seizures) and stroke within last 6 months
  12. Active gastrointestinal ulceration or bleeding within the last 6 months unless related to underlying malignant disease
  13. Renal outflow obstruction, macroscopic or significant microscopic hematuria
  14. Active infectious diseases considered by investigator to be incompatible with protocol
  15. Major surgery within 28 days
  16. Autoimmune diseases requiring steroids at a dose above 10 mg prednisolone equivalent or other immunosuppressants
  17. Pregnant or breastfeeding women
  18. Psychiatric disorders, drug and/or alcohol abuse
  19. Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
  20. Known hypersensitivity to GEM3PSCA excipients
  21. Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
  22. Incapability of understanding purpose and possible consequences of the trial
  23. Patients who should not be included according to the opinion of the investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Susann Helas, Dr. +49 351 4466 4500 ext 0 gem3psca-01@gemoab.com
Contact: Martina Raupach
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03927573
Other Study ID Numbers  ICMJE GEM3PSCA-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party GEMoaB Monoclonals GmbH
Study Sponsor  ICMJE GEMoaB Monoclonals GmbH
Collaborators  ICMJE GCP-Service International Ltd. & Co. KG
Investigators  ICMJE
Principal Investigator: Ralf Bargou, Prof. Dr. Universitätsklinikum Würzburg, CCC Mainfranken
PRS Account GEMoaB Monoclonals GmbH
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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