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

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

A first-in-human study using NJH395 in non-breast HER2-positive advanced malignancies

Study Overview

• Status: Completed
• Conditions: NON-breast HER2+ Malignancies
• Intervention / Treatment: Drug: NJH395

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: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NJH395; Includes non-breast HER2-positive advanced malignancies	Drug: NJH395; Immune stimulator antibody conjugate (ISAC), consisting of a monoclonal antibody which targets HER2 conjugated to an immune-stimulatory agent

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Plain language summaries are available on this link

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2018
• Primary Completion (Actual): October 19, 2020
• Study Completion (Actual): October 19, 2020

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): February 4, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Phase I, NJH395, HER2+, ISAC, TLR7
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CNJH395X2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No