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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03927573
• Other study ID #: GEM3PSCA-01
• Status: Terminated
• Phase: Phase 1
• Start date: April 15, 2019
• Est. completion date: June 28, 2023

Study information

• Verified date: July 2023
• Source: AvenCell Europe GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: June 28, 2023
• Est. primary completion date: June 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female patients, = 18 years of age

2. 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

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) = 90 % 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 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)

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

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Non-small Cell Lung Cancer
• Prostate Cancer
• Renal Cancer
• Transitional Cell Carcinoma

Intervention

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

Locations

Country	Name	City	State
Germany	Universitätsklinikum Dresden	Dresden	Sachsen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Marburg	Marburg	Hessen
Germany	Klinikum rechts der Isar der TU München	Munich	Bayern
Germany	Universitätsklinikum Würzburg	Würzburg	Bayern

Sponsors (2)

Lead Sponsor	Collaborator
AvenCell Europe GmbH	GCP-Service International Ltd. & Co. KG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Incidence and intensity of adverse events	graded according to CTCAE V4.03	End of Treatment (EOT) +14 days (DLT period)
Primary	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	Recommended phase 2 dose (RP2D)	The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.	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)
Secondary	Antitumor activity of GEM3PSCA according to RECIST1.1 (Response Evaluation Criteria in Solid Tumors)	response rates	End of Treatment (EOT) +14 days (DLT period)
Secondary	Prostate specific antigen (PSA) response in patients with prostate cancer		End of Treatment (EOT) +14 days (DLT period)
Secondary	Overall survival (OS)		End of Treatment (EOT) + 14 days (DLT period)
Secondary	Influence on circulating tumor cells in patients with prostate cancer		Day 8 / End of Treatment (EOT)