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

JRCT ID: jRCT2080224562

Registered date:14/02/2019

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: Non-small Cell Lung Cancer (NSCLC), Triple Negative Breast Cancer (TNBC), Pancreatic Ductal Adenocarcinoma (PDAC), Renal Cell Carcinoma (RCC), Ovarian Cancer, Colorectal Cancer Microsatellite Stable (MSS), Metastatic Castration Resistant Prostate Cancer (mCRPC)
• Date of first enrollment: 05/12/2018
• Target sample size: 344
• Countries of recruitment: Asia except Japan,North America,Europe,Japan
• Study type: Interventional

Intervention(s)

NZV930 Single Arm: NZV930 Monotherapy
NZV930 Combination arm: NZV930 with PDR001 Doublet Therapy, NZV930 with NIR178 Doublet Therapy and NZV930 with NIR178 & PDR001 Triplet Therapy

NZV930: Specified dose on specified days, intravenous
PDR001: Specified dose on specified days, intravenous
NIR178: Specified dose on specified days, Orally

Outcome(s)

Primary Outcome

-To characterize the safety and tolerability of NZV930 as a single agent and in combination with PDR001 and/or NIR178 in patients with advanced malignancies.
-To determine the recommended dose (RD) for expansion for single agent NZV930 and in combinations with PDR001 and/or NIR178.

Secondary Outcome

-To assess the preliminary anti-tumor activity of NZV930 as a single agent and in combination with PDR001 and/or NIR178.
-To characterize the pharmacokinetics (PK) of NZV930 as a single agent and NZV930, PDR001 and/or NIR178 in combination.
-To assess the immunogenicity of NZV930 and PDR001.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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

Related Information

• Primary Sponsor: Novartis Pharma K.K.
• Secondary Sponsor: -
• Source(s) of Monetary Support: -
• Secondary ID(s): NCT03549000,JapicCTI-194631