Phase 1 Study of Single Agent GBR 1302 in Subjects With HER2 Positive Cancers

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety profile and maximum tolerable dose (MTD) of GBR 1302 monotherapy in subjects with HER2 positive cancers

Official Title
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A Phase 1, First-in-man, Multicenter, Open-label, Dose-escalation Study of Single-agent GBR 1302 in Subjects With HER2 Positive Cancers

Conditions
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HER2 Expressing Solid Tumours

Intervention / Treatment
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* Drug: CD3/HER2 bispecific monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Progressive HER2 positive solid tumours (immunohistochemistry [IHC] positive or equivocal) with no available standard or curative treatment. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2. Exclusion Criteria: Active infectious disease considered by the Investigator to be incompatible with the protocol. Patients not recovered from any therapy-related toxicities from previous therapies to at least CTCAE ≤ Grade 1 except in case of liver metastases or Gilbert's Syndrome or alopecia. Brain metastases that are symptomatic or untreated or that require current therapy. Previous treatment with immunotherapy within 8 weeks of starting study medication, chemotherapy, radiotherapy, molecular-targeted therapy, or biological therapies (including HER2 directed therapies) within 4 weeks of starting study medication, or hormone therapy within 2 weeks of starting study medication. Use of any investigational drug within the past 4 weeks before start of study medication or concomitantly with this study except for investigational immune-stimulatory therapy (e.g. checkpoint-regulator targeted treatment). The minimum washout period should be 8 weeks before starting the study medication.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBR 1302<br>Dose escalation | Drug: CD3/HER2 bispecific monoclonal antibody<br>* Increasing doses, IV on day 1 and 15 of each 28 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Tolerated Dose (MTD) of GBR 1302 | Number of DLTs (dose limiting toxicities) after the first two administrations of study drug (i.e. Cycle 1) in each cohort | 28 Days | 
| The relationship of the dose of GBR 1302 with the incidence, nature, and intensity of AEs according to CTCAEv4.03 |  | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) for solid tumors. |  | 2 cycles, 56 days | 
| Disease control rate (DCR) for solid tumors |  | 2 cycles, 56 days | 
| Duration of disease control (measured from drug start date to the date of disease progression or death for subjects who had CR or PR or SD during treatment). |  | At least 56 days | 
| Maximum Concentration (Cmax) of GBR 1302 |  | 28 Days | 
| Time to Maximum Concentration (Tmax) of GBR 1302 |  | 28 Days | 
| Area Under Curve [AUC0-t and AUC0-tau] of GBR 1302 |  | 28 Days | 
| Immunogenicity of GBR 1302 in terms of ADA formation assessed compared to baseline |  | 28 Days |