NON-breast HER2+ Malignancies
Conditions
Keywords
Phase I, NJH395, HER2+, ISAC, TLR7
Brief summary
A first-in-human study using NJH395 in non-breast HER2-positive advanced malignancies
Detailed description
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.
Interventions
DRUGNJH395
Immune stimulator antibody conjugate (ISAC), consisting of a monoclonal antibody which targets HER2 conjugated to an immune-stimulatory agent
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of dose limiting toxicities (DLTs) | 21 days | The time frame will expand to 42 days for the second part of the study |
| Number of participants with Adverse Events | 2.5 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) parameter (AUC) for NJH395 | 126 days | — |
| Incidence of anti-NJH395 antibodies and neutralizing antibodies to trastuzumab | 126 days | — |
| Overall Response Rate | 2.5 years | Response assessed by RECIST v1.1 and iRECIST |
| Concentration versus time profiles for NJH395 and its catabolite | 126 days | — |
| Progression Free Survival (PFS) | 2.5 years | Time from start of treatment to date of the first documented progression or death in months |
| Duration of Response (DOR) | 2.5 years | Response assessed by RECIST v1.1 and iRECIST |
| Characterization of tumor-infiltrating lymphocytes by IHC | 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) | Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8). |
| Clinical Benefit Rate (CBR) | 2.5 years | Response assessed by RECIST v1.1 and iRECIST |
| PK parameter (Cmax) for NJH395 | 126 days | — |
Countries
Italy, Japan, South Korea, United States
Outcome results
None listed