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

Ovarian Cancer Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03549000
• Other study ID #: CNZV930X2101
• Secondary ID: 2018-000153-51
• Status: Terminated
• Phase: Phase 1
• Start date: July 18, 2018
• Est. completion date: October 17, 2022

Study information

• Verified date: October 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 127
• Est. completion date: October 17, 2022
• Est. primary completion date: October 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Colorectal Cancer Microsatellite Stable (MSS)
• Metastatic Castration Resistant Prostate Cancer (mCRPC)
• Non-small Cell Lung Cancer (NSCLC)
• Ovarian Cancer
• Pancreatic Ductal Adenocarcinoma (PDAC)
• Renal Cell Carcinoma (RCC)
• Triple Negative Breast Cancer (TNBC)
• Triple Negative Breast Neoplasms

Intervention

Other:
• NZV930
NZV930, Specified dose on specified days, intravenous (IV)
• PDR001
PDR001, Specified dose on specified days, intravenous (IV)

Drug:
• NIR178
NIR178 Specified dose on specified days, Orally

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
United Kingdom	Novartis Investigative Site	Sutton	Surrey
United States	University of Texas MD Anderson Cancer Center MD Anderson PSC	Houston	Texas
United States	H Lee Moffitt Cancer Center and Research Institute Inc	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Japan,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate (ORR)	Defined as the proportion of patients with best overall response of CR or PR	3 years
Secondary	Clinical Benefit Rate (CBR)	Defined as the proportion of patients with best overall response of CR, PR or SD >= 16 weeks	3 years
Secondary	Progression Free Survival (PFS)	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	3 years
Secondary	Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.	Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.	3 years
Secondary	Plasma concentration vs. time profiles for NIR178 and derived PK parameters	Concentration time profile of NIR178 and its metabolites	3 years
Secondary	To assess the immunogenicity of NZV930 and PDR001	Presence and titer of anti-drug antibodies, anti-NZV930 and anti-PDR001 in (patients receiving combination with PDR001).	3 years

External Links

•   Study Results