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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02947165
• Other study ID #: CNIS793X2101
• Secondary ID: 2016-003044-36
• Status: Completed
• Phase: Phase 1
• Start date: April 25, 2017
• Est. completion date: June 18, 2021

Study information

• Verified date: January 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: June 18, 2021
• Est. primary completion date: June 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Hepatocellular
• Colorectal Cancer
• Hepatocellular Cancer
• Kidney Neoplasms
• Liver Neoplasms
• Lung Cancer
• Pancreatic Cancer
• Renal Cancer

Intervention

Drug:
• NIS793
Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.
• PDR001
Anti-PD-1 antibody tested on a Q3W regimen or alternative Q4W regimen.

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Salzburg
Canada	Novartis Investigative Site	Toronto	Ontario
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wuerzburg
Hong Kong	Novartis Investigative Site	Hong Kong
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Japan	Novartis Investigative Site	Kashiwa	Chiba
Switzerland	Novartis Investigative Site	St. Gallen
Taiwan	Novartis Investigative Site	Taipei
United States	Sarah Cannon Research Institute SC	Nashville	Tennessee
United States	Huntsman Cancer Institute SC	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany,  Hong Kong,  Italy,  Japan,  Switzerland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793		Up to 90 days after end of treatment
Primary	Incidence of DLTs, AEs, SAEs and dose reductions/interruptions for NIS793 in combination with PDR001		Up to 150 days after end of treatment
Secondary	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).	48 months
Secondary	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).	48 months
Secondary	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).	48 months
Secondary	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.	48 months
Secondary	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).	48 months
Secondary	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.	48 months
Secondary	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.	48 months
Secondary	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.	48 months
Secondary	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.	48 months
Secondary	Cmax for NIS793 single agent and NIS793 in combination with PDR001.	Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.	48 months
Secondary	Tmax for NIS793 single agent and NIS793 in combination with PDR001.	Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.	48 months
Secondary	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.	48 months
Secondary	Characterization of tumor infiltrating lymphocytes (TILs) by H&E	Assess change from baseline of immune infiltrates in tumor biopsies after 2 cycles of treatment.	48 months
Secondary	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.	48 months