Clinical trial NCT03696771: Study to Determine Safety and Dose of NJH395 in Non-breast HER2+ Advanced Cancer
Official title: A Phase I, Multicenter, Open-label Dose Finding Study of NJH395, Administered Intravenously in Patients With Non-breast HER2+ Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: NON-breast HER2+ Malignancies
Keywords: Phase I, NJH395, HER2+, ISAC, TLR7
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-10-05
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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/exclusion criteria may apply.

Primary outcomes:
measure: Incidence and severity of dose limiting toxicities (DLTs)
timeFrame: 21 days
measure: Number of participants with Adverse Events
timeFrame: 2.5 years
Secondary outcomes:
measure: Concentration versus time profiles for NJH395 and its catabolite
timeFrame: 126 days
measure: PK parameter (Cmax) for NJH395
timeFrame: 126 days
measure: Pharmacokinetic (PK) parameter (AUC) for NJH395
timeFrame: 126 days
measure: Incidence of anti-NJH395 antibodies and neutralizing antibodies to trastuzumab
timeFrame: 126 days
measure: Overall Response Rate
timeFrame: 2.5 years
measure: Clinical Benefit Rate (CBR)
timeFrame: 2.5 years
measure: Progression Free Survival (PFS)
timeFrame: 2.5 years
measure: Duration of Response (DOR)
timeFrame: 2.5 years
measure: Characterization of tumor-infiltrating lymphocytes by IHC
timeFrame: 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)
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
Study officials:
References: