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

Primary Purpose

Breast Cancer, Lung Cancer, Hepatocellular Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
NIS793
PDR001
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sarah Cannon Research Institute SC
  • Huntsman Cancer Institute SC
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

NIS793

NIS793 + PDR001

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Best overall response (BOR)
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).
Disease control rate (DCR)
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).
Overall response rate (ORR)
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).
Progression free survival (PFS)
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.
Duration of response (DOR)
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).
Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001
Evaluate serum concentration of NIS793 and PDR001 up to 8 cycles after start of treatment and at end of treatment.
Presence of anti-NIS793 and anti-PDR001 antibodies
Assess the emergence of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.
Concentration of anti-NIS793 and anti-PDR001 antibodies
Assess the concentration of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.
Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Cmax for NIS793 single agent and NIS793 in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Tmax for NIS793 single agent and NIS793 in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Half life of NIS793 as single agent and in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Characterization of tumor infiltrating lymphocytes (TILs) by H&E
Assess change from baseline of immune infiltrates in tumor biopsies after 2 cycles of treatment.
Characterization of tumor infiltrating lymphocytes by immunohistochemistry using markers such as CD8 and PD-L1
Assess change from baseline in immunological markers in tumor biopsies after 2 cycles of treatment.

Full Information

First Posted
October 18, 2016
Last Updated
January 28, 2022
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02947165
Brief Title
Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
April 25, 2017 (Actual)
Primary Completion Date
June 18, 2021 (Actual)
Study Completion Date
June 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Lung Cancer, Hepatocellular Cancer, Colorectal Cancer, Pancreatic Cancer, Renal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NIS793
Arm Type
Experimental
Arm Title
NIS793 + PDR001
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
NIS793
Intervention Description
Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.
Intervention Type
Drug
Intervention Name(s)
PDR001
Intervention Description
Anti-PD-1 antibody tested on a Q3W regimen or alternative Q4W regimen.
Primary Outcome Measure Information:
Title
Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793
Time Frame
Up to 90 days after end of treatment
Title
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 Measure Information:
Title
Best overall response (BOR)
Description
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).
Time Frame
48 months
Title
Disease control rate (DCR)
Description
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).
Time Frame
48 months
Title
Overall response rate (ORR)
Description
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).
Time Frame
48 months
Title
Progression free survival (PFS)
Description
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.
Time Frame
48 months
Title
Duration of response (DOR)
Description
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).
Time Frame
48 months
Title
Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001
Description
Evaluate serum concentration of NIS793 and PDR001 up to 8 cycles after start of treatment and at end of treatment.
Time Frame
48 months
Title
Presence of anti-NIS793 and anti-PDR001 antibodies
Description
Assess the emergence of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.
Time Frame
48 months
Title
Concentration of anti-NIS793 and anti-PDR001 antibodies
Description
Assess the concentration of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.
Time Frame
48 months
Title
Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.
Description
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Time Frame
48 months
Title
Cmax for NIS793 single agent and NIS793 in combination with PDR001.
Description
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Time Frame
48 months
Title
Tmax for NIS793 single agent and NIS793 in combination with PDR001.
Description
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Time Frame
48 months
Title
Half life of NIS793 as single agent and in combination with PDR001.
Description
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Time Frame
48 months
Title
Characterization of tumor infiltrating lymphocytes (TILs) by H&E
Description
Assess change from baseline of immune infiltrates in tumor biopsies after 2 cycles of treatment.
Time Frame
48 months
Title
Characterization of tumor infiltrating lymphocytes by immunohistochemistry using markers such as CD8 and PD-L1
Description
Assess change from baseline in immunological markers in tumor biopsies after 2 cycles of treatment.
Time Frame
48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Sarah Cannon Research Institute SC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Huntsman Cancer Institute SC
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C1
Country
Canada
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Novartis Investigative Site
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277 8577
Country
Japan
Facility Name
Novartis Investigative Site
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30832732
Citation
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.
Results Reference
derived

Learn more about this trial

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

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