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

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ClinicalTrials.gov Identifier: NCT03549000
Recruitment Status : Recruiting
First Posted : June 7, 2018
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is 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

Condition or disease Intervention/treatment Phase
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) Other: NZV930 Other: PDR001 Drug: NIR178 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 344 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : July 18, 2018
Estimated Primary Completion Date : January 24, 2022
Estimated Study Completion Date : February 14, 2022


Arm Intervention/treatment
Experimental: NZV930 Monotherapy
Single Agent NZV930
Other: NZV930
NZV930, Specified dose on specified days, intravenous (IV)
Other Name: Biological

Experimental: NZV930 with PDR001 Doublet Therapy
Combination of NZV930 with PDR001
Other: NZV930
NZV930, Specified dose on specified days, intravenous (IV)
Other Name: Biological

Other: PDR001
PDR001, Specified dose on specified days, intravenous (IV)
Other Name: Biological

Experimental: NZV930 with NIR178 Doublet Therapy
Combination of NZV930 with NIR178
Other: NZV930
NZV930, Specified dose on specified days, intravenous (IV)
Other Name: Biological

Drug: NIR178
NIR178 Specified dose on specified days, Orally

Experimental: NZV930 with NIR178 & PDR001 Triplet Therapy
Combination of NZV930 with NIR178 and PDR001
Other: NZV930
NZV930, Specified dose on specified days, intravenous (IV)
Other Name: Biological

Other: PDR001
PDR001, Specified dose on specified days, intravenous (IV)
Other Name: Biological

Drug: NIR178
NIR178 Specified dose on specified days, Orally




Primary Outcome Measures :
  1. Number of participants with adverse events as a measure of safety and tolerability of the NZV930 in combination with PDR001 and/or NIR178 [ Time Frame: 3 years ]
    Incidence and severity of AEs and SAEs, incl. changes in laboratory parameters, vital signs, and ECGs Dose limiting toxicity in cycle 1 (28 days) for single agent NZV930 and NZV930 in combination with PDR001 and/or NIR178 during dose escalation phase only Tolerability: dose interruptions Tolerability: dose reductions Tolerability: dose intensity


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 3 years ]
    Defined as the proportion of patients with best overall response of CR or PR

  2. Clinical Benefit Rate (CBR) [ Time Frame: 3 years ]
    Defined as the proportion of patients with best overall response of CR, PR or SD >= 16 weeks

  3. Progression Free Survival (PFS) [ Time Frame: 3 years ]
    Defined as the time from the date of start of treatment to the date of the event defined as first documented progression or death due to any cause

  4. Serum concentration vs. time profiles of NZV930 (free drug) and PDR001. [ Time Frame: 3 years ]
    Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.

  5. Plasma concentration vs. time profiles for NIR178 and derived PK parameters [ Time Frame: 3 years ]
    Concentration time profile of NIR178 and its metabolites

  6. To assess the immunogenicity of NZV930 and PDR001 [ Time Frame: 3 years ]
    Presence and titer of anti-drug antibodies, anti-NZV930 and anti-PDR001 in (patients receiving combination with PDR001).

  7. Characterize changes in the immune infiltrate in tumors [ Time Frame: 3 years ]
    Change from baseline in tumor infiltrating lymphocytes (TILs), tumor associated macrophages (TAMs), CD8+ T-cells, and PDL-1 expression



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03549000


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Florida
Novartis Investigative Site Recruiting
Tampa, Florida, United States, 33612
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 1Z6
Japan
Novartis Investigative Site Recruiting
Chuo ku, Tokyo, Japan, 104 0045
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Madrid, Spain, 28009
United Kingdom
Novartis Investigative Site Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03549000     History of Changes
Other Study ID Numbers: CNZV930X2101
2018-000153-51 ( EudraCT Number )
First Posted: June 7, 2018    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
NZV930
PDR001
NIR178
Immune checkpoint inhibitor
immunotherapy
CD73
PD-1
PD-L1
A2aR
Adenosine

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Adenocarcinoma
Carcinoma, Renal Cell
Triple Negative Breast Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases