Non-small Cell Lung Cancer (NSCLC)Phase 1NCT03549000
A Phase I/Ib Study of NZV930 Alone and in Combination With PDR001 and /or NIR178 in Patients With Advanced Malignancies.
A Phase 1 study testing NZV930, PDR001 and NIR178 in people with Non-small Cell Lung Cancer (NSCLC) and Triple Negative Breast Cancer (TNBC), run by Novartis Pharmaceuticals at 10 sites in 7 countries.
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer (NSCLC), Triple Negative Breast Cancer (TNBC), Pancreatic Ductal Adenocarcinoma (PDAC)
- What is being tested?
- NZV930, PDR001 and NIR178
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 18 Jul 2018to 17 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
United States2 sites
University of Texas MD Anderson Cancer Center MD Anderson PSC
Houston, Texas, 77030
H Lee Moffitt Cancer Center and Research Institute Inc
Tampa, Florida, 33612
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H2W 1T8
Novartis Investigative Site
Toronto, Ontario, M5G 1Z6
Spain2 sites
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Valencia, Valencia, 46010
United Kingdom1 site
Novartis Investigative Site
Sutton, Surrey, SM2 5PT
About this study
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.
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)
- Being tested
- NZV930, PDR001, NIR178
- Keywords
- NZV930, PDR001, NIR178, Immune checkpoint inhibitor, immunotherapy, CD73, PD-1, PD-L1, A2aR, Adenosine
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Ovarian Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NZV930Other
Also called Biological
NZV930, Specified dose on specified days, intravenous (IV)
PDR001Other
Also called Biological
PDR001, Specified dose on specified days, intravenous (IV)
NIR178Drug
NIR178 Specified dose on specified days, Orally
| Study group | Role | What they receive |
|---|---|---|
| NZV930 Monotherapy | Experimental | Single Agent NZV930 Receives: Other: NZV930 |
| NZV930 with PDR001 Doublet Therapy | Experimental | Combination of NZV930 with PDR001 Receives: Other: NZV930; Other: PDR001 |
| NZV930 with NIR178 Doublet Therapy | Experimental | Combination of NZV930 with NIR178 Receives: Other: NZV930; Drug: NIR178 |
| NZV930 with NIR178 & PDR001 Triplet Therapy | Experimental | Combination of NZV930 with NIR178 and PDR001 Receives: Other: NZV930; Other: PDR001; Drug: NIR178 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 years
Secondary outcomes (6)
Overall response rate (ORR)
Defined as the proportion of patients with best overall response of CR or PR
Measured: 3 years
Clinical Benefit Rate (CBR)
Defined as the proportion of patients with best overall response of CR, PR or SD >= 16 weeks
Measured: 3 years
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
Measured: 3 years
Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.
Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.
Measured: 3 years
Plasma concentration vs. time profiles for NIR178 and derived PK parameters
Concentration time profile of NIR178 and its metabolites
Measured: 3 years
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).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2018
- Study start18 Jul 2018
- Primary completion17 Oct 2022
- Study completion17 Oct 2022
Why it stopped: After review of data which showed low likelihood of efficacy in these patients Novartis decided to terminate the trial early. Termination was not safety related
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549000
- Sponsor's protocol ID
- CNZV930X2101
- Other IDs
- 2018-000153-51, 2018
- Status last verified
- Dec 2024
- First submitted
- 25 May 2018
- Last updated
- 13 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03549000
- Acronym / sponsor ID
- CNZV930X2101
- 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)
- Keywords
- NZV930, PDR001, NIR178, Immune checkpoint inhibitor, immunotherapy, CD73, PD-1, PD-L1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After review of data which showed low likelihood of efficacy in these patients Novartis decided to terminate the trial early. Termination was not safety related
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 18 Jul 2018 (actual)
- Primary completion
- 17 Oct 2022 (actual)
- Study completion
- 17 Oct 2022 (actual)
- First posted
- 7 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NZV930 Monotherapy | Experimental | Other: NZV930Single Agent NZV930 |
| NZV930 with PDR001 Doublet Therapy | Experimental | Other: NZV930, Other: PDR001Combination of NZV930 with PDR001 |
| NZV930 with NIR178 Doublet Therapy | Experimental | Other: NZV930, Drug: NIR178Combination of NZV930 with NIR178 |
| NZV930 with NIR178 & PDR001 Triplet Therapy | Experimental | Other: NZV930, Other: PDR001, Drug: NIR178Combination of NZV930 with NIR178 and PDR001 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NZV930Also: BiologicalNZV930, Specified dose on specified days, intravenous (IV) | Other | NZV930 Monotherapy, NZV930 with NIR178 & PDR001 Triplet Therapy, NZV930 with NIR178 Doublet Therapy, NZV930 with PDR001 Doublet Therapy |
| PDR001Also: BiologicalPDR001, Specified dose on specified days, intravenous (IV) | Other | NZV930 with NIR178 & PDR001 Triplet Therapy, NZV930 with PDR001 Doublet Therapy |
| NIR178NIR178 Specified dose on specified days, Orally | Drug | NZV930 with NIR178 & PDR001 Triplet Therapy, NZV930 with NIR178 Doublet Therapy |
Primary outcome
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
6 secondary outcomes
Overall response rate (ORR)
Time frame: 3 years
Clinical Benefit Rate (CBR)
Time frame: 3 years
Progression Free Survival (PFS)
Time frame: 3 years
Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.
Time frame: 3 years
Plasma concentration vs. time profiles for NIR178 and derived PK parameters
Time frame: 3 years
To assess the immunogenicity of NZV930 and PDR001
Time frame: 3 years
Results and safety
The study was stopped early (reason given: After review of data which showed low likelihood of efficacy in these patients Novartis decided to terminate the trial early. Termination was not safety related). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- Study ResultsLink provided by the sponsor.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NZV930, PDR001 and NIR178 in people with Non-small Cell Lung Cancer (NSCLC) and Triple Negative Breast Cancer (TNBC), run by Novartis Pharmaceuticals at 10 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada, Spain, Australia, Japan and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: After review of data which showed low likelihood of efficacy in these patients Novartis decided to terminate the trial early. Termination was not safety related). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.