NCT02947165

Brief Summary

To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline
Completed

Started Apr 2017

Typical duration for phase_1 breast-cancer

Geographic Reach
9 countries

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 18, 2016

Completed
9 days until next milestone

First Posted

Study publicly available on registry

October 27, 2016

Completed
6 months until next milestone

Study Start

First participant enrolled

April 25, 2017

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 18, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 18, 2021

Completed
Last Updated

January 31, 2022

Status Verified

January 1, 2022

Enrollment Period

4.2 years

First QC Date

October 18, 2016

Last Update Submit

January 28, 2022

Conditions

Breast CancerLung CancerHepatocellular CancerColorectal CancerPancreatic CancerRenal Cancer

Outcome Measures

Primary Outcomes (2)

  • Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793

    Up to 90 days after end of treatment

  • Incidence of DLTs, AEs, SAEs and dose reductions/interruptions for NIS793 in combination with PDR001

    Up to 150 days after end of treatment

Secondary Outcomes (14)

  • Best overall response (BOR)

    48 months

  • Disease control rate (DCR)

    48 months

  • Overall response rate (ORR)

    48 months

  • Progression free survival (PFS)

    48 months

  • Duration of response (DOR)

    48 months

  • +9 more secondary outcomes

Study Arms (2)

NIS793

EXPERIMENTAL
Drug: NIS793

NIS793 + PDR001

EXPERIMENTAL
Drug: NIS793Drug: PDR001

Interventions

NIS793DRUG

Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.

NIS793NIS793 + PDR001
PDR001DRUG

Anti-PD-1 antibody tested on a Q3W regimen or alternative Q4W regimen.

NIS793 + PDR001

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent must be obtained prior to any screening procedures.
  • Patient (male or female) ≥ 18 years of age.
  • Escalation: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
  • Expansion: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed despite standard therapy following their last prior therapy or are intolerant to standard therapy and fit into one of the following groups: Group 1: NSCLC resistant to anti-PD-1/PD-L1; Group 2: TNBC; Group 3: HCC; Group 4: MSS-CRC; Group 5: pancreatic; Group 6 ccRCC resistant to anti-PD-1/PD-L1.
  • Resistance to anti-PD-1/PD-L1 therapy is defined as: Documented progressive disease occurring while on/or within 6 months after anti-PD-1 and/or anti-PD-L1 agent (single or combination) received as the last therapy prior to enrollment.
  • ECOG Performance Status ≤ 2.
  • Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. Patient must be willing to undergo a new tumor biopsy at screening, and during therapy on this study. Exceptions may be made on a case by case basis after documented discussion with Novartis.

You may not qualify if:

  • History of severe hypersensitivity reactions to study treatment ingredients or other monoclonal antibodies and components of study drug.
  • Patients with active, known or suspected autoimmune disease. Note: Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • HIV infection.
  • Active HBV or HCV infection.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Sarah Cannon Research Institute SC

Nashville, Tennessee, 37203, United States

Location

Huntsman Cancer Institute SC

Salt Lake City, Utah, 84112, United States

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2C1, Canada

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Publications (2)

  • Bauer TM, Santoro A, Lin CC, Garrido-Laguna I, Joerger M, Greil R, Spreafico A, Yau T, Goebeler ME, Hutter-Kronke ML, Perotti A, Juif PE, Lu D, Barys L, Cremasco V, Pelletier M, Evans H, Fabre C, Doi T. Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-beta monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors. J Immunother Cancer. 2023 Nov 29;11(11):e007353. doi: 10.1136/jitc-2023-007353.

    PMID: 38030303DERIVED

  • Dodagatta-Marri E, Meyer DS, Reeves MQ, Paniagua R, To MD, Binnewies M, Broz ML, Mori H, Wu D, Adoumie M, Del Rosario R, Li O, Buchmann T, Liang B, Malato J, Arce Vargus F, Sheppard D, Hann BC, Mirza A, Quezada SA, Rosenblum MD, Krummel MF, Balmain A, Akhurst RJ. alpha-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by alpha-TGFbeta antibody to promote durable rejection and immunity in squamous cell carcinomas. J Immunother Cancer. 2019 Mar 4;7(1):62. doi: 10.1186/s40425-018-0493-9.

    PMID: 30832732DERIVED

MeSH Terms

Conditions

Breast NeoplasmsLung NeoplasmsLiver NeoplasmsColorectal NeoplasmsPancreatic NeoplasmsKidney Neoplasms

Interventions

NIS-793spartalizumab

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesDigestive System NeoplasmsDigestive System DiseasesLiver DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesEndocrine Gland NeoplasmsPancreatic DiseasesEndocrine System DiseasesUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

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
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 18, 2016

First Posted

October 27, 2016

Study Start

April 25, 2017

Primary Completion

June 18, 2021

Study Completion

June 18, 2021

Last Updated

January 31, 2022

Record last verified: 2022-01

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)JP(1)AU(1)HK(1)DE(2)CA(1)US(2)IT(2)TW(1)