Study to Determine Safety and Dose of NJH395 in Non-breast HER2+ Advanced Cancer

Study Overview
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Brief Summary
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A first-in-human study using NJH395 in non-breast HER2-positive advanced malignancies

Detailed Description
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This study has two parts. There will be a single dose of NJH395 in the first part and multiple doses of NJH395 in the second part. After the first part is completed, the second part may open.

Official Title
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A Phase I, Multicenter, Open-label Dose Finding Study of NJH395, Administered Intravenously in Patients With Non-breast HER2+ Advanced Malignancies

Conditions
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NON-breast HER2+ Malignancies

Intervention / Treatment
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* Drug: NJH395


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patient must have known histologically or cytologically confirmed and documented HER2-positive solid tumor excluding patients with breast cancer Advanced/metastatic cancer with measurable disease as determined by RECIST v.1.1 who have progressed or are intolerant to all approved therapies known to confer clinical benefit. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy prior to therapy, and during therapy on this study. Key Exclusion Criteria: History of severe hypersensitivity to any ingredient of study drug, trastuzumab or other monoclonal antibody. Patients previously treated with TLR 7/8 agonist. Impaired cardiac function or history of clinically significant cardiac disease Active, known or suspected autoimmune disease. Human Immunodeficiency virus (HIV) infection History of or current interstitial lung disease or pneumonitis Grade 2 or greater. Discontinued prior checkpoint inhibitor due to a checkpoint inhibitor related toxicity. Currently receiving medications known to cause Torsades de Pointe that cannot be discontinued 7 days prior to starting treatment Other protocol defined inclusion/exclusion criteria may apply.

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: NJH395<br>Includes non-breast HER2-positive advanced malignancies | Drug: NJH395<br>* Immune stimulator antibody conjugate (ISAC), consisting of a monoclonal antibody which targets HER2 conjugated to an immune-stimulatory agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of dose limiting toxicities (DLTs) | The time frame will expand to 42 days for the second part of the study | 21 days | 
| Number of participants with Adverse Events |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration versus time profiles for NJH395 and its catabolite |  | 126 days | 
| PK parameter (Cmax) for NJH395 |  | 126 days | 
| Pharmacokinetic (PK) parameter (AUC) for NJH395 |  | 126 days | 
| Incidence of anti-NJH395 antibodies and neutralizing antibodies to trastuzumab |  | 126 days | 
| Overall Response Rate | Response assessed by RECIST v1.1 and iRECIST | 2.5 years | 
| Clinical Benefit Rate (CBR) | Response assessed by RECIST v1.1 and iRECIST | 2.5 years | 
| Progression Free Survival (PFS) | Time from start of treatment to date of the first documented progression or death in months | 2.5 years | 
| Duration of Response (DOR) | Response assessed by RECIST v1.1 and iRECIST | 2.5 years | 
| Characterization of tumor-infiltrating lymphocytes by IHC | Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8). | Cycle 1 Day 5, Cycle 2 Day 1 (each cycle is 21 days), Cycle 8 Day 1 and at end of treatment (expected between months 6 and 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, NJH395, HER2+, ISAC, TLR7