A Phase I/Ib Study of NIZ985 in Combination With PDR001 in Adults With Metastatic Cancers

NCT02452268 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CNIZ985X2102JNIZ985X2102J
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 7

Brief 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

Conditions

Metastatic and Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Assess the dose-limiting toxicity of the single agent NIZ985 and the combination of PDR001

  28 days

Secondary Outcomes (4)

• Determine the maximum tolerated dose (MTD) of hetIL-15 as determined by DLTs during Cycle 1.

  28 days

• Determine the pharmacokinetic (PK) profile of hetIL-15, including T½

  28 days

• Determine the pharmacokinetic (PK) profile of hetIL-15, including Cmax.

  28 Days

• Determine the preliminary anti-tumor activity of hetIL-15

  8 weeks

Study Arms (2)

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.

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.

Drug: PDR001

Interventions

NIZ985 DRUG

Subcutaneous administration of hetIL-15 three times a week for two consecutive weeks

Also known as: IL-15/sIL-15Ra, heterodimeric IL-15

NIZ985

PDR001 DRUG

• PDR001 is a human monoclonal antibody (MAb) administered day 1 of each cycle

NIZ985 + PDR001

Eligibility Criteria

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

You may qualify if:

• 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%).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

National Cancer Institute National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Washington University School of Medicine SC

St Louis, Missouri, 63110, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43212, United States

Location

Providence Portland Medical Center SC

Portland, Oregon, 97123, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98105, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• 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.

  PMID: 37907221 DERIVED

• Conlon 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.

  PMID: 34799399 DERIVED

• Watson 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.

  PMID: 29474450 DERIVED

Related Links

• Study Results

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: May 22, 2015
• Study Start: May 8, 2017
• Primary Completion: March 7, 2022
• Study Completion: March 7, 2022
• Last Updated: March 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)