Clinical trial NCT02947165: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lung Cancer
Hepatocellular Cancer
Colorectal Cancer
Pancreatic Cancer
Renal Cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-10-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793
timeFrame: Up to 90 days after end of treatment
measure: Incidence of DLTs, AEs, SAEs and dose reductions/interruptions for NIS793 in combination with PDR001
timeFrame: Up to 150 days after end of treatment
Secondary outcomes:
measure: Best overall response (BOR)
timeFrame: 48 months
measure: Disease control rate (DCR)
timeFrame: 48 months
measure: Overall response rate (ORR)
timeFrame: 48 months
measure: Progression free survival (PFS)
timeFrame: 48 months
measure: Duration of response (DOR)
timeFrame: 48 months
measure: Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001
timeFrame: 48 months
measure: Presence of anti-NIS793 and anti-PDR001 antibodies
timeFrame: 48 months
measure: Concentration of anti-NIS793 and anti-PDR001 antibodies
timeFrame: 48 months
measure: Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.
timeFrame: 48 months
measure: Cmax for NIS793 single agent and NIS793 in combination with PDR001.
timeFrame: 48 months
measure: Tmax for NIS793 single agent and NIS793 in combination with PDR001.
timeFrame: 48 months
measure: Half life of NIS793 as single agent and in combination with PDR001.
timeFrame: 48 months
measure: Characterization of tumor infiltrating lymphocytes (TILs) by H&E
timeFrame: 48 months
measure: Characterization of tumor infiltrating lymphocytes by immunohistochemistry using markers such as CD8 and PD-L1
timeFrame: 48 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute SC
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute SC
state: Utah
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.