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

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

September 4, 2018

First Posted Date ^ICMJE

October 5, 2018

Last Update Posted Date

October 5, 2018

Actual Study Start Date ^ICMJE

November 20, 2018

Estimated Primary Completion Date

May 10, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Incidence and severity of dose limiting toxicities (DLTs)[ Time Frame: 21 days ]

The time frame will expand to 42 days for the second part of the study

Number of participants with Adverse Events[ Time Frame: 2.5 years ]

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Concentration versus time profiles for NJH395 and its catabolite[ Time Frame: 126 days ]
PK parameter (Cmax) for NJH395[ Time Frame: 126 days ]
Pharmacokinetic (PK) parameter (AUC) for NJH395[ Time Frame: 126 days ]
Incidence of anti-NJH395 antibodies and neutralizing antibodies to trastuzumab[ Time Frame: 126 days ]
Overall Response Rate[ Time Frame: 2.5 years ]
Response assessed by RECIST v1.1 and iRECIST
Clinical Benefit Rate (CBR)[ Time Frame: 2.5 years ]
Response assessed by RECIST v1.1 and iRECIST
Progression Free Survival (PFS)[ Time Frame: 2.5 years ]
Time from start of treatment to date of the first documented progression or death in months
Duration of Response (DOR)[ Time Frame: 2.5 years ]
Response assessed by RECIST v1.1 and iRECIST
Characterization of tumor-infiltrating lymphocytes by IHC[ Time Frame: 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).

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Allocation:
Intervention Model: Single Group Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: NJH395
Immune stimulator antibody conjugate (ISAC), consisting of a monoclonal antibody which targets HER2 conjugated to an immune-stimulatory agent

Study Arms

Experimental: NJH395
Includes non-breast HER2-positive advanced malignancies

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

May 10, 2021

Estimated Primary Completion Date

May 10, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Novartis Pharmaceuticals

Collaborators ^ICMJE

Investigators ^ICMJE

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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