A Phase I/Ib Study of NZV930 Alone and in Combination With PDR001 and /or NIR178 in Patients With Advanced Malignancies.

NCT ID: NCT03549000

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-18

Study Completion Date

2022-10-17

Brief Summary

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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

Detailed Description

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Conditions

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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

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NZV930 PDR001 NIR178 Immune checkpoint inhibitor immunotherapy CD73 PD-1 PD-L1 A2aR Adenosine

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NZV930 Monotherapy

Single Agent NZV930

Group Type EXPERIMENTAL

NZV930

Intervention Type OTHER

NZV930, Specified dose on specified days, intravenous (IV)

NZV930 with PDR001 Doublet Therapy

Combination of NZV930 with PDR001

Group Type EXPERIMENTAL

NZV930

Intervention Type OTHER

NZV930, Specified dose on specified days, intravenous (IV)

PDR001

Intervention Type OTHER

PDR001, Specified dose on specified days, intravenous (IV)

NZV930 with NIR178 Doublet Therapy

Combination of NZV930 with NIR178

Group Type EXPERIMENTAL

NZV930

Intervention Type OTHER

NZV930, Specified dose on specified days, intravenous (IV)

NIR178

Intervention Type DRUG

NIR178 Specified dose on specified days, Orally

NZV930 with NIR178 & PDR001 Triplet Therapy

Combination of NZV930 with NIR178 and PDR001

Group Type EXPERIMENTAL

NZV930

Intervention Type OTHER

NZV930, Specified dose on specified days, intravenous (IV)

PDR001

Intervention Type OTHER

PDR001, Specified dose on specified days, intravenous (IV)

NIR178

Intervention Type DRUG

NIR178 Specified dose on specified days, Orally

Interventions

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NZV930

NZV930, Specified dose on specified days, intravenous (IV)

Intervention Type OTHER

PDR001

PDR001, Specified dose on specified days, intravenous (IV)

Intervention Type OTHER

NIR178

NIR178 Specified dose on specified days, Orally

Intervention Type DRUG

Other Intervention Names

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Biological Biological

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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H Lee Moffitt Cancer Center and Research Institute Inc

Tampa, Florida, United States

Site Status

University of Texas MD Anderson Cancer Center MD Anderson PSC

Houston, Texas, United States

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Sutton, Surrey, United Kingdom

Site Status

Countries

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United States Australia Canada Japan Singapore Spain United Kingdom

Related Links

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Other Identifiers

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2018-000153-51

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CNZV930X2101

Identifier Type: -

Identifier Source: org_study_id