Clinical trial NCT03549000: A Phase I/Ib Study of NZV930 Alone and in Combination With PDR001 and /or NIR178 in Patients With Advanced Malignancies.
Official title: A Phase I/Ib, Open-label, Multi-center, Study of NZV930 as a Single Agent and in Combination With PDR001 and/or NIR178 in Patients With Advanced Malignancies.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer (NSCLC)
Triple Negative Breast Cancer (TNBC)
Pancreatic Ductal Adenocarcinoma (PDAC)
Colorectal Cancer Microsatellite Stable (MSS)
Ovarian Cancer
Renal Cell Carcinoma (RCC)
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Keywords: NZV930
PDR001
NIR178
Immune checkpoint inhibitor
immunotherapy
CD73
PD-1
PD-L1
A2aR
Adenosine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-06-07
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess the safety, tolerability, and preliminary anti-tumor activity of experimental medication NZV930 alone and when combined with PDR001 and/or NIR178, in patients with advanced cancers


Eligibility criteria: Inclusion Criteria:

Adult men \& women ≥ 18 years of age Histologically confirmed advanced malignancies with documented progression following standard therapy, or for whom, in the opinion of the investigator, no appropriate standard therapy exists.

Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. The patient must be willing to undergo a new tumor biopsy at screening and during treatment.

ECOG performance status 0-2 and in the opinion of the investigator, likely to complete at least 56 days of treatment.

Exclusion Criteria:

Symptomatic or uncontrolled Brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.

Patients with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment prior to study entry and at doses of \<10 mg per day prednisolone or equivalent for at least 2 weeks before administration of any study treatment.

Patients who required discontinuation of treatment due to treatment-related toxicities with prior immunotherapy.

Patients previously treated with anti-CD73 treatment and/or adenosine receptor A2a (A2aR) inhibitors.

Active, previously documented, or suspected autoimmune disease within the past 2 years.

Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur should not be excluded. Additionally, patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.

History of or current drug-induced interstitial lung disease or pneumonitis grade ≥ 2.

Impaired cardiovascular function or clinically significant cardiovascular disease, including any of the following: Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia Patients with corrected QT using the Fridericia's correction (QTcF) \> 470 msec for females or \>450 msec for males, on screening ECG or congenital long QT syndrome Acute myocardial infarction or unstable angina \< 3 months prior to study entry History of stroke or transient ischemic event requiring medical therapy Symptomatic claudication Infection: HIV infection, Active HBV or HCV infection (per institutional guidelines). Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in the expansion but not in the escalation, Known history of tuberculosis Infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed treatment before screening is initiated.

Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 6 weeks is indicated as washout period. For patients receiving anticancer immunotherapies, 4 weeks is indicated as the washout period.

Systemic chronic steroid therapy (≥ 10 mg/day prednisone or equivalent) or any immunosuppressive therapy, other than replacement dose steroids in the setting of adrenal insufficiency, within 7 days of the first dose of study treatment. Topical, inhaled, nasal, and ophthalmic steroids are allowed

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability of the NZV930 in combination with PDR001 and/or NIR178
timeFrame: 3 years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 3 years
measure: Clinical Benefit Rate (CBR)
timeFrame: 3 years
measure: Progression Free Survival (PFS)
timeFrame: 3 years
measure: Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.
timeFrame: 3 years
measure: Plasma concentration vs. time profiles for NIR178 and derived PK parameters
timeFrame: 3 years
measure: To assess the immunogenicity of NZV930 and PDR001
timeFrame: 3 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute Inc
state: Florida
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center MD Anderson PSC
state: Texas
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Sutton
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: