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Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.

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ClinicalTrials.gov Identifier: NCT02947165
Recruitment Status : Recruiting
First Posted : October 27, 2016
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Cancer Lung Cancer Hepatocellular Cancer Colorectal Cancer Pancreatic Cancer Renal Cancer Drug: NIS793 Drug: PDR001 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/Ib, Open-label, Multi-center Dose Escalation Study of NIS793 in Combination With PDR001 in Adult Patients With Advanced Malignancies
Actual Study Start Date : April 25, 2017
Estimated Primary Completion Date : April 13, 2021
Estimated Study Completion Date : April 13, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: NIS793 Drug: NIS793
Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.
Experimental: NIS793 + PDR001 Drug: NIS793
Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.

Drug: PDR001
Anti-PD-1 antibody tested on a Q3W regimen or alternative Q4W regimen.


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793 [ Time Frame: Up to 90 days after end of treatment ]
  2. Incidence of DLTs, AEs, SAEs and dose reductions/interruptions for NIS793 in combination with PDR001 [ Time Frame: Up to 150 days after end of treatment ]

Secondary Outcome Measures :
  1. Best overall response (BOR) [ Time Frame: 48 months ]
    Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).

  2. Disease control rate (DCR) [ Time Frame: 48 months ]
    Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).

  3. Overall response rate (ORR) [ Time Frame: 48 months ]
    Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).

  4. Progression free survival (PFS) [ Time Frame: 48 months ]
    Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment. During disease progression f/u, every 8 weeks for 40 weeks, then every 12 weeks.

  5. Duration of response (DOR) [ Time Frame: 48 months ]
    Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).

  6. Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001 [ Time Frame: 48 months ]
    Evaluate serum concentration of NIS793 and PDR001 up to 8 cycles after start of treatment and at end of treatment.

  7. Presence of anti-NIS793 and anti-PDR001 antibodies [ Time Frame: 48 months ]
    Assess the emergence of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.

  8. Concentration of anti-NIS793 and anti-PDR001 antibodies [ Time Frame: 48 months ]
    Assess the concentration of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.

  9. Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001. [ Time Frame: 48 months ]
    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  10. Cmax for NIS793 single agent and NIS793 in combination with PDR001. [ Time Frame: 48 months ]
    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  11. Tmax for NIS793 single agent and NIS793 in combination with PDR001. [ Time Frame: 48 months ]
    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  12. Half life of NIS793 as single agent and in combination with PDR001. [ Time Frame: 48 months ]
    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  13. Characterization of tumor infiltrating lymphocytes (TILs) by H&E [ Time Frame: 48 months ]
    Assess change from baseline of immune infiltrates in tumor biopsies after 2 cycles of treatment.

  14. Characterization of tumor infiltrating lymphocytes by immunohistochemistry using markers such as CD8 and PD-L1 [ Time Frame: 48 months ]
    Assess change from baseline in immunological markers in tumor biopsies after 2 cycles of treatment.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained prior to any screening procedures.
  2. Patient (male or female) ≥ 18 years of age.
  3. 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.

  4. 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.

  5. ECOG Performance Status ≤ 2.
  6. 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.

Exclusion Criteria:

  1. History of severe hypersensitivity reactions to study treatment ingredients or other monoclonal antibodies and components of study drug.
  2. 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.
  3. HIV infection.
  4. Active HBV or HCV infection.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02947165


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Tennessee
Novartis Investigative Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: Vicky Weikal       Vicky.Weikal@sarahcannon.com   
Principal Investigator: Todd M. Bauer         
United States, Utah
Novartis Investigative Site Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Jessica Norton    801-213-4217    Jessica.norton@hci.utah.edu   
Principal Investigator: Ignacio Garrido Laguna         
Austria
Novartis Investigative Site Recruiting
Salzburg, Austria, 5020
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M6G 1Z5
Germany
Novartis Investigative Site Recruiting
Ulm, Germany, 89081
Novartis Investigative Site Recruiting
Wuerzburg, Germany, 97080
Hong Kong
Novartis Investigative Site Recruiting
Hong Kong, Hong Kong
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20132
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site Recruiting
Kashiwa, Chiba, Japan, 277 8577
Switzerland
Novartis Investigative Site Recruiting
St. Gallen, Switzerland, 9007
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02947165    
Other Study ID Numbers: CNIS793X2101
2016-003044-36 ( EudraCT Number )
First Posted: October 27, 2016    Key Record Dates
Last Update Posted: January 21, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Neoplasms
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Urologic Neoplasms
 Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Diseases