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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 )

Tracking Information
First Submitted Date  ICMJE May 25, 2018
First Posted Date  ICMJE June 7, 2018
Last Update Posted Date April 11, 2019
Actual Study Start Date  ICMJE July 18, 2018
Estimated Primary Completion Date January 24, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 25, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03549000 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 25, 2018)
  • Overall response rate (ORR) [ Time Frame: 3 years ]
    Defined as the proportion of patients with best overall response of CR or PR
  • 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
  • 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
  • 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.
  • Plasma concentration vs. time profiles for NIR178 and derived PK parameters [ Time Frame: 3 years ]
    Concentration time profile of NIR178 and its metabolites
  • 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).
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I/Ib Study of NZV930 Alone and in Combination With PDR001 and /or NIR178 in Patients With Advanced Malignancies.
Official Title  ICMJE 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.
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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)
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: NZV930 Monotherapy
    Single Agent NZV930
    Intervention: Other: NZV930
  • Experimental: NZV930 with PDR001 Doublet Therapy
    Combination of NZV930 with PDR001
    Interventions:
    • Other: NZV930
    • Other: PDR001
  • Experimental: NZV930 with NIR178 Doublet Therapy
    Combination of NZV930 with NIR178
    Interventions:
    • Other: NZV930
    • Drug: NIR178
  • Experimental: NZV930 with NIR178 & PDR001 Triplet Therapy
    Combination of NZV930 with NIR178 and PDR001
    Interventions:
    • Other: NZV930
    • Other: PDR001
    • Drug: NIR178
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 25, 2018)
344
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 14, 2022
Estimated Primary Completion Date January 24, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Canada,   Japan,   Singapore,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03549000
Other Study ID Numbers  ICMJE CNZV930X2101
2018-000153-51 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP