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

NCT03549000 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CNZV930X21012018-000153-51
• Study Type: interventional
• Target: 127
• Locations: 7 countries
• Sites: 10

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

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

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events as a measure of safety and tolerability of the NZV930 in combination with PDR001 and/or NIR178

  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

  3 years

Secondary Outcomes (6)

• Overall response rate (ORR)

  3 years

• Clinical Benefit Rate (CBR)

  3 years

• Progression Free Survival (PFS)

  3 years

• Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.

  3 years

• Plasma concentration vs. time profiles for NIR178 and derived PK parameters

  3 years

Study Arms (4)

NZV930 Monotherapy

EXPERIMENTAL

Single Agent NZV930

Other: NZV930

NZV930 with PDR001 Doublet Therapy

EXPERIMENTAL

Combination of NZV930 with PDR001

Other: NZV930; Other: PDR001

NZV930 with NIR178 Doublet Therapy

EXPERIMENTAL

Combination of NZV930 with NIR178

Other: NZV930; Drug: NIR178

NZV930 with NIR178 & PDR001 Triplet Therapy

EXPERIMENTAL

Combination of NZV930 with NIR178 and PDR001

Other: NZV930; Other: PDR001; Drug: NIR178

Interventions

NZV930 OTHER

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

Also known as: Biological

NZV930 Monotherapy; NZV930 with NIR178 & PDR001 Triplet Therapy; NZV930 with NIR178 Doublet Therapy; NZV930 with PDR001 Doublet Therapy

PDR001 OTHER

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

Also known as: Biological

NZV930 with NIR178 & PDR001 Triplet Therapy; NZV930 with PDR001 Doublet Therapy

NIR178 DRUG

NIR178 Specified dose on specified days, Orally

NZV930 with NIR178 & PDR001 Triplet Therapy; NZV930 with NIR178 Doublet Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

H Lee Moffitt Cancer Center and Research Institute Inc

Tampa, Florida, 33612, United States

Location

University of Texas MD Anderson Cancer Center MD Anderson PSC

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1Z6, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Links

• Study Results
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell

Interventions

Biological Products; spartalizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 7, 2018
• Study Start: July 18, 2018
• Primary Completion: October 17, 2022
• Study Completion: October 17, 2022
• Last Updated: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (2); CA (2); AU (1); SG (1); JP (1); ES (2)