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

Phase 1

Completed

• Conditions: Breast Cancer; Colorectal Cancer; Lung Cancer; Renal Cancer; Hepatocellular Cancer; Pancreatic Cancer
• Interventions: Drug: NIS793; Drug: PDR001

• Registration Number: NCT02947165
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-10-18
• Study First Submitted QC: 2016-10-25
• Study First Posted: 2016-10-27
• Study Start: 2017-04-25
• Primary Completion: 2021-06-18
• Study Completion: 2021-06-18
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-28
• Last Update Posted: 2022-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NIS793	NIS793	-
NIS793 + PDR001	PDR001	-
NIS793 + PDR001	NIS793	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Cmax for NIS793 single agent and NIS793 in combination with PDR001.	48 months	Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Presence of anti-NIS793 and anti-PDR001 antibodies	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.
Best overall response (BOR)	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).
Overall response rate (ORR)	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).
Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.	48 months	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.	48 months	Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Characterization of tumor infiltrating lymphocytes (TILs) by H&E	48 months	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	48 months	Assess change from baseline in immunological markers in tumor biopsies after 2 cycles of treatment.
Disease control rate (DCR)	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).
Concentration of anti-NIS793 and anti-PDR001 antibodies	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.
Progression free survival (PFS)	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.
Duration of response (DOR)	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).
Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001	48 months	Evaluate serum concentration of NIS793 and PDR001 up to 8 cycles after start of treatment and at end of treatment.
Tmax for NIS793 single agent and NIS793 in combination with PDR001.	48 months	Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

Trial Locations

Locations (3)

Sarah Cannon Research Institute SC; 🇺🇸 Nashville, Tennessee, United States

Huntsman Cancer Institute SC; 🇺🇸 Salt Lake City, Utah, United States

Novartis Investigative Site; 🇨🇳 Taipei, Taiwan