A Phase I/Ib Study of NIZ985 Alone and in Combination With Spartalizumab

NCT04261439 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CNIZ985B121012019-004069-42
• Study Type: interventional
• Target: 60
• Locations: 7 countries
• Sites: 9

Brief Summary

The purpose of this phase I/Ib study was to determine the safety profile of NIZ985 (new formulation), and if it could be safely combined with spartalizumab or tislelizumab and to determine the appropriate dose and schedule for further study. Moreover, the study characterized the pharmacokinetic profiles of NIZ985 as a single agent and in combination with spartalizumab or tislelizumab and identified preliminary anti-tumor activity.

Conditions

In Escalation: All Patients With Solid Tumors and Lymphoma; In Expansion: Melanoma, Non-small Cell Lung Cancer

Keywords

NIZ985; Spartalizumab; Tislelizumab; immunotherapy; checkpoint Inhibitor; checkpoint inhibitor resistance; melanoma; NSCLC

Outcome Measures

Primary Outcomes (4)

• Incidence of Dose Limiting Toxcities (DLTs) in escalation and expansion

  Incidence of DLTs in Cycle 1 (28 days) in escalation and expansion

  1 cycle (28 days)

• Number of patients with and severity of adverse events (AEs) and serious adverse events (SAEs)

  AEs and SAEs including changes in laboratory parameters, vital signs and electrocardiograms (ECGs) qualifying and reported as AEs for all patients from escalation and expansion

  24 months

• Dose interruptions and reductions

  Number of dose interruptions and dose reductions of NIZ985, spartalizumab and tislelizumab.

  24 months

• Dose intensity

  Dose intensity as a ratio of cumulative dose received during duration of exposure over duration of exposure for NIZ985, spartalizumab and tislelizumab.

  24 months

Secondary Outcomes (7)

• Overall response Rate (ORR)

  24 months

• Best Overall Response (BOR)

  24 months

• Disease control Rate (DCR)

  24 months

• Progression Free Survival (PFS) (expansion groups only)

  24 months

• Duration of Response (DOR) (expansion groups only)

  24 months

Study Arms (2)

Arm 1

EXPERIMENTAL

Single agent arm. NIZ985 is administered as a single agent (subjects may be treated with the NIZ985-Spartalizumab combination after their first disease re-evaluation)

Drug: NIZ985; Drug: Spartalizumab

Arm 2

EXPERIMENTAL

Combination arm. NIZ985 and Spartalizumab combination is administered starting at Cycle 1 Day 1 in dose escalation. NIZ985 and tislelizumab combination is administered starting at Cycle 1 Day 1 in dose expansion.

Drug: NIZ985; Drug: Spartalizumab; Drug: Tislelizumab

Interventions

NIZ985 DRUG

NIZ985 injection

Arm 1; Arm 2

Spartalizumab DRUG

Spartalizumab infusion

Also known as: PDR001

Arm 1; Arm 2

Tislelizumab DRUG

Tislelizumab infusion

Also known as: VDT482

Arm 2

Eligibility Criteria

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

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• Male or female patients ≥ 18 years of age
• Histologically confirmed and documented advanced solid tumors and lymphoma (includes locally advanced malignancies that are not curable by surgery or radiotherapy, and those with metastatic disease) with documented progression following standard therapy, and for whom, no standard therapy is available, tolerated or appropriate. Disease must be measurable as determined by RECIST 1.1 (refer to Appendix 1) or Cheson et al (2014) (refer to Appendix 6).
• Escalation: Patients previously treated with CPI (anti PD-1/PD-L1 and/or anti CTLA-4) who have previously responded and progressed at any time prior to enrollment. Previous response is an initial radiographic CR/PR (a confirmatory scan is not required). If the most recent regimen included CPI, patients with SD lasting ≥ 6 months are also eligible.
• Expansion in melanoma: Patients with cutaneous melanoma previously treated with CPI (anti PD 1/ PD-L1 and/or anti CTLA-4) who have previously responded and progressed at any time prior to enrollment. Previous response is radiographic CR/PR (a confirmatory scan is not required). If the most recent regimen included CPI, patients with SD lasting ≥ 6 months are also eligible.
• Expansion in NSCLC: Patients with locally advanced or unresectable NSCLC who have been treated with up to 2 prior lines of therapies, at least one of which was a CPI-containing regimen (anti PD 1/ PD-L1 and/or anti CTLA-4). Patients must have previously responded to CPI and progressed at any time prior to enrollment. Previous response is radiographic CR/PR (a confirmatory scan is not required). If the most recent regimen included CPI, patients with SD lasting ≥ 6 months are also eligible. Patients with actionable mutations will be excluded.
• Patients must be willing and able to comply with the protocol for the duration of the study
• Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening and during therapy on the study.
• ECOG performance status ≤1 and in the opinion of the investigator, likely to complete at least 28 days of treatment.

You may not qualify if:

• Patients that have received any prior IL-15 treatment.
• History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients. In addition, patients with a history of immune mediated toxicities from CPI that led to permanent discontinuation of CPI treatment will be excluded.
• Patients with primary CNS tumors are excluded. Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry. Patients with treated symptomatic brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study entry) and at a dose of ≤ 10 mg per day prednisone or equivalent for at least 2 weeks before administration of any study treatment.
• Systemic chronic steroid therapy (\> 10mg/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.
• Malignant disease, other than that being treated in this study, that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or other tumors that will not affect life expectancy.
• Patients having out of range lab values during screening and before the first dose of study treatment. Out of range lab values are defined as:
• Absolute neutrophil count (ANC) \<1.0 x 109/L
• Platelets \<75 x 109/L
• Hemoglobin (Hgb) \< 9 g/dL
• Serum creatinine \> 1.5 x ULN or creatinine clearance \< 60mL/min using Cockcroft-Gault formula (See Appendix 3)
• Total bilirubin \> 1.5 x ULN, (except for patients with Gilbert's syndrome \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN)
• Aspartate transaminase (AST) \> 3 x ULN
• Alanine transaminase (ALT) \> 3x ULN
• Serum electrolytes ≥ grade 2 despite adequate supplementation.
• Impaired cardiovascular function or clinically significant cardiovascular disease, including any of the following:

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

City of Hope National Medical

Duarte, California, 91010, United States

Location

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Taipei, 10048, Taiwan

Location

Related Links

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

MeSH Terms

Conditions

Lymphoma; Carcinoma, Non-Small-Cell Lung; Melanoma

Interventions

spartalizumab; tislelizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

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: February 6, 2020
• First Posted: February 7, 2020
• Study Start: February 27, 2020
• Primary Completion: December 27, 2023
• Study Completion: December 27, 2023
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (2); TW (1); BE (1); DE (1); JP (1); IT (1)