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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-small Cell Lung Cancer, Prostate Cancer, Renal Cancer, Transitional Cell Carcinoma

Intervention / Treatment
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* Drug: GEM3PSCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Autoimmune diseases requiring steroids at a dose above 10 mg prednisolone equivalent or other immunosuppressants Pregnant or breastfeeding women Psychiatric disorders, drug and/or alcohol abuse Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) Known hypersensitivity to GEM3PSCA excipients Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance) Incapability of understanding purpose and possible consequences of the trial Patients who should not be included according to the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEM3PSCA<br>Application of GEM3PSCA, a PSCA targeted bispecific antibody engaging T-cells | Drug: GEM3PSCA<br>* Infusion of GEM3PSCA, administered intravenously, continuously over 7 days, 2 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Antitumor activity of GEM3PSCA according to RECIST1.1 (Response Evaluation Criteria in Solid Tumors) | response rates | 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) |