Metastatic and Advanced Solid TumorsPhase 1NCT02452268
A Phase I/Ib Study of NIZ985 in Combination With PDR001 in Adults With Metastatic Cancers
A Phase 1 study testing NIZ985 and PDR001 in people with Metastatic and Advanced Solid Tumors, run by Novartis Pharmaceuticals at 7 sites in United States.
Trial summary
Phase I/Ib multicenter clinical trial. Single agent dose escalation of NIZ985 followed by expansion. Second escalation of NIZ985 in combination with PDR001 followed by expansion Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic and Advanced Solid Tumors
- What is being tested?
- NIZ985 and PDR001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 7 sitesUnited States
- Study dates
- 8 May 2017to 7 Mar 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
- Histologically confirmed solid tumor malignancy that is metastatic or unresectable and have progressed on at least 1 prior therapy and for whom standard curative or palliative measures do not exist or are associated with minimal subject survival benefit.
- Evaluable or measurable disease, defined as by Response Evaluation Criteria in Solid Tumors (RECIST).
- Recovered to ≤ grade 1 NCI CTCAE version 4.0 from toxicity of prior chemotherapy or biologic therapy administered more than 4 weeks earlier.
- Subjects on bisphosphonates for any cancer or on hormone therapy for prostate cancer may continue this therapy. However, subjects with prostate cancer must have confirmed metastatic disease that has progressed despite hormonal therapy producing castrate levels of testosterone.
- Age ≥18 years.
- ECOG performance status ≤1 (Karnofsky ≥70%).
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- Normal organ and marrow function:
- leukocytes ≥3,000/mcL
- absolute neutrophil count (ANC) ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin within normal institutional limits
- AST/ALT ≤2.5 × ULN
- creatinine <1.5 × institutional ULN OR
- creatinine clearance ≥60 mL/min/1.73 m2 for subjects with serum creatinine levels >1.5 × higher than ULN.
- DLCO/VA and FEV1 ≥ 50% of predicted on PFTs.
- Subjects with inactive central nervous system (CNS) metastasis are eligible..
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, during the treatment portion of the study and for 4 months after completion of hetIL-15 administration.
- Able to provide written informed consent.
- Life expectancy > 3 months.
Who cannot join
- Prior IL-15 treatment or cytotoxic therapy, immunotherapy, radiotherapy, major surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks prior or for checkpoint inhibitors such as anti-CTLA-4 or anti PD1/PD-L1 or nitrosoureas or mitomycin C for 6 weeks prior to C1D1.
- Primary brain cancers or active CNS metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to hetIL-15.
- Concurrent anticancer therapy (including other investigational agents) with the exception of hormone therapy for prostate cancer.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cognitive impairment, active substance abuse, or psychiatric illness/social situations that, in the view of the Investigator, would preclude safe treatment or the ability to give informed consent and limit compliance with study requirements.
- HIV positive patients.
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- Positive hepatitis B or C serology.
- History of severe asthma or absolute requirement for chronic inhaled corticosteroid medications.
- History of autoimmune disease, with the exception of an autoimmune event associated with prior ipilimumab (anti-CTLA-4) therapy that has been completely resolved for more than 4 weeks prior to C1D1.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
National Cancer Institute National Cancer Institute
Bethesda, Maryland, 20892
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43212
University of Wisconsin
Madison, Wisconsin, 53792
Providence Portland Medical Center SC
Portland, Oregon, 97123
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Seattle Cancer Care Alliance
Seattle, Washington, 98105
Washington University School of Medicine SC
St Louis, Missouri, 63110
About this study
Official title: A Phase 1 Study of Subcutaneous Recombinant Human NIZ985 ((hetIL-15) (IL15/sIL-15Ra)) Alone and in Combination With PDR001 in Adults With Metastatic Cancers
Phase I/Ib multicenter clinical trial. Single agent dose escalation of NIZ985 followed by expansion. Second escalation of NIZ985 in combination with PDR001 followed by expansion
- Conditions
- Metastatic and Advanced Solid Tumors
- Being tested
- NIZ985, PDR001
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIZ985Drug
Also called IL-15/sIL-15Ra, heterodimeric IL-15
Subcutaneous administration of hetIL-15 three times a week for two consecutive weeks
PDR001Drug
- PDR001 is a human monoclonal antibody (MAb) administered day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| NIZ985 | Experimental | * Single treatment arm, dose escalation administered subcutaneously (SC) on MWF for 2 consecutive weeks.
* Cycle length 28 days.
* Occurrence of a dose-limiting toxicity (DLT) leads to the expansion to 6 subjects.
* MTD is the dose prior to the dose level where ≥ 2/6 subjects have a DLT.
* Following identification of the MTD / RDE, dose expansion will follow. Receives: Drug: NIZ985 |
| NIZ985 + PDR001 | Experimental | * The phase Ib dose escalation portion of the study will consist of a fixed dose (400 mg, IV infusion, Q4W) of PDR001 and escalating doses of NIZ985 (hetIL-15) to evaluate safety, tolerability and determine the MTD and/or RDE of the combination to be used in expansion cohorts.
* On days when PDR001 and NIZ985 are administered on the same day, PDR001 will be administered first. NIZ985 will be administered after the PDR001 infusion has been completed.
* Information on the preparation and administration of PDR001 is found in the PDR001 pharmacy manual. Receives: Drug: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the dose-limiting toxicity of the single agent NIZ985 and the combination of PDR001
Measured: 28 days
Secondary outcomes (4)
Determine the maximum tolerated dose (MTD) of hetIL-15 as determined by DLTs during Cycle 1.
Measured: 28 days
Determine the pharmacokinetic (PK) profile of hetIL-15, including T½
Measured: 28 days
Determine the pharmacokinetic (PK) profile of hetIL-15, including Cmax.
Measured: 28 Days
Determine the preliminary anti-tumor activity of hetIL-15
Best overall response (BOR) per RECIST and irRC
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2015 (estimated)
- Study start8 May 2017
- Primary completion7 Mar 2022
- Study completion7 Mar 2022
Why it stopped: business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic and Advanced Solid TumorsStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 83 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
- NCT02452268
- Sponsor's protocol ID
- CNIZ985X2102J
- Other IDs
- NIZ985X2102J
- Status last verified
- Mar 2023
- First submitted
- 2 Mar 2015
- Last updated
- 3 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Leidner R, Conlon K, McNeel DG, Wang-Gillam A, Gupta S, Wesolowski R, Chaudhari M, Hassounah N, Lee JB, Ho Lee L, O'Keeffe JA, Lewis N, Pavlakis GN, Thompson JA. First-in-human phase I/Ib study of NIZ985, a recombinant heterodimer of IL-15 and IL-15Ralpha, as a single agent and in combination with spartalizumab in patients with advanced and metastatic solid tumors. J Immunother Cancer. 2023 Oct;11(10):e007725. doi: 10.1136/jitc-2023-007725.
PubMed 37907221Conlon K, Watson DC, Waldmann TA, Valentin A, Bergamaschi C, Felber BK, Peer CJ, Figg WD, Potter EL, Roederer M, McNeel DG, Thompson JA, Gupta S, Leidner R, Wang-Gillam A, Parikh NS, Long D, Kurtulus S, Ho Lee L, Chowdhury NR, Bender F, Pavlakis GN. Phase I study of single agent NIZ985, a recombinant heterodimeric IL-15 agonist, in adult patients with metastatic or unresectable solid tumors. J Immunother Cancer. 2021 Nov;9(11):e003388. doi: 10.1136/jitc-2021-003388.
PubMed 34799399Watson DC, Moysi E, Valentin A, Bergamaschi C, Devasundaram S, Fortis SP, Bear J, Chertova E, Bess J Jr, Sowder R, Venzon DJ, Deleage C, Estes JD, Lifson JD, Petrovas C, Felber BK, Pavlakis GN. Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes. PLoS Pathog. 2018 Feb 23;14(2):e1006902. doi: 10.1371/journal.ppat.1006902. eCollection 2018 Feb.
PubMed 29474450
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Subcutaneous Recombinant Human NIZ985 ((hetIL-15) (IL15/sIL-15Ra)) Alone and in Combination With PDR001 in Adults With Metastatic Cancers
- ClinicalTrials.gov ID
- NCT02452268
- Acronym / sponsor ID
- CNIZ985X2102J
- Conditions
- Metastatic and Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: business decision
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 May 2017 (actual)
- Primary completion
- 7 Mar 2022 (actual)
- Study completion
- 7 Mar 2022 (actual)
- First posted
- 22 May 2015 (estimated)
- 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.
Phase I/Ib multicenter clinical trial. Single agent dose escalation of NIZ985 followed by expansion. Second escalation of NIZ985 in combination with PDR001 followed by expansion
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NIZ985 | Experimental | Drug: NIZ985* Single treatment arm, dose escalation administered subcutaneously (SC) on MWF for 2 consecutive weeks. * Cycle length 28 days. * Occurrence of a dose-limiting toxicity (DLT) leads to the expansion to 6 subjects. * MTD is the dose prior to the dose level where ≥ 2/6 subjects have a DLT. * Following identification of the MTD / RDE, dose expansion will follow. |
| NIZ985 + PDR001 | Experimental | Drug: PDR001* The phase Ib dose escalation portion of the study will consist of a fixed dose (400 mg, IV infusion, Q4W) of PDR001 and escalating doses of NIZ985 (hetIL-15) to evaluate safety, tolerability and determine the MTD and/or RDE of the combination to be used in expansion cohorts. * On days when PDR001 and NIZ985 are administered on the same day, PDR001 will be administered first. NIZ985 will be administered after the PDR001 infusion has been completed. * Information on the preparation and administration of PDR001 is found in the PDR001 pharmacy manual. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically confirmed solid tumor malignancy that is metastatic or unresectable and have progressed on at least 1 prior therapy and for whom standard curative or palliative measures do not exist or are associated with minimal subject survival benefit.
- Evaluable or measurable disease, defined as by Response Evaluation Criteria in Solid Tumors (RECIST).
- Recovered to ≤ grade 1 NCI CTCAE version 4.0 from toxicity of prior chemotherapy or biologic therapy administered more than 4 weeks earlier.
- Subjects on bisphosphonates for any cancer or on hormone therapy for prostate cancer may continue this therapy. However, subjects with prostate cancer must have confirmed metastatic disease that has progressed despite hormonal therapy producing castrate levels of testosterone.
- Age ≥18 years.
Key exclusion criteria (9 listed)
- Prior IL-15 treatment or cytotoxic therapy, immunotherapy, radiotherapy, major surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks prior or for checkpoint inhibitors such as anti-CTLA-4 or anti PD1/PD-L1 or nitrosoureas or mitomycin C for 6 weeks prior to C1D1.
- Primary brain cancers or active CNS metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to hetIL-15.
- Concurrent anticancer therapy (including other investigational agents) with the exception of hormone therapy for prostate cancer.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cognitive impairment, active substance abuse, or psychiatric illness/social situations that, in the view of the Investigator, would preclude safe treatment or the ability to give informed consent and limit compliance with study requirements.
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 |
|---|---|---|
| NIZ985Also: IL-15/sIL-15Ra, heterodimeric IL-15Subcutaneous administration of hetIL-15 three times a week for two consecutive weeks | Drug | NIZ985 |
| PDR001• PDR001 is a human monoclonal antibody (MAb) administered day 1 of each cycle | Drug | NIZ985 + PDR001 |
Primary outcome
Assess the dose-limiting toxicity of the single agent NIZ985 and the combination of PDR001
Time frame: 28 days
4 secondary outcomes
Determine the maximum tolerated dose (MTD) of hetIL-15 as determined by DLTs during Cycle 1.
Time frame: 28 days
Determine the pharmacokinetic (PK) profile of hetIL-15, including T½
Time frame: 28 days
Determine the pharmacokinetic (PK) profile of hetIL-15, including Cmax.
Time frame: 28 Days
Determine the preliminary anti-tumor activity of hetIL-15
Time frame: 8 weeks
Results and safety
The study was stopped early (reason given: business decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2023.
- Derived from this study: PubMed 37907221Leidner R, Conlon K, McNeel DG, Wang-Gillam A, Gupta S, Wesolowski R, Chaudhari M, Hassounah N, Lee JB, Ho Lee L, O'Keeffe JA, Lewis N, Pavlakis GN, Thompson JA. First-in-human phase I/Ib study of NIZ985, a recombinant heterodimer of IL-15 and IL-15Ralpha, as a single agent and in combination with spartalizumab in patients with advanced and metastatic solid tumors. J Immunother Cancer. 2023 Oct;11(10):e007725. doi: 10.1136/jitc-2023-007725.
- Derived from this study: PubMed 34799399Conlon K, Watson DC, Waldmann TA, Valentin A, Bergamaschi C, Felber BK, Peer CJ, Figg WD, Potter EL, Roederer M, McNeel DG, Thompson JA, Gupta S, Leidner R, Wang-Gillam A, Parikh NS, Long D, Kurtulus S, Ho Lee L, Chowdhury NR, Bender F, Pavlakis GN. Phase I study of single agent NIZ985, a recombinant heterodimeric IL-15 agonist, in adult patients with metastatic or unresectable solid tumors. J Immunother Cancer. 2021 Nov;9(11):e003388. doi: 10.1136/jitc-2021-003388.
- Derived from this study: PubMed 29474450Watson DC, Moysi E, Valentin A, Bergamaschi C, Devasundaram S, Fortis SP, Bear J, Chertova E, Bess J Jr, Sowder R, Venzon DJ, Deleage C, Estes JD, Lifson JD, Petrovas C, Felber BK, Pavlakis GN. Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes. PLoS Pathog. 2018 Feb 23;14(2):e1006902. doi: 10.1371/journal.ppat.1006902. eCollection 2018 Feb.
- Study ResultsLink 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
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NIZ985 and PDR001 in people with Metastatic and Advanced Solid Tumors, run by Novartis Pharmaceuticals at 7 sites in United States.
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 19 inclusion and 9 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 3 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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: business decision). 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?
Assess the dose-limiting toxicity of the single agent NIZ985 and the combination of PDR001 (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02452268, which also lists 3 linked publications.
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 3 Mar 2023; AzTrials last refreshed its copy on 6 Nov 2026.