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

Novartis Pharmaceuticals120 enrolled

Overview

To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

Breast Cancer Lung Cancer Hepatocellular Cancer Colorectal Cancer Pancreatic Cancer Renal Cancer

Interventions

NIS793DRUG

Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.

PDR001DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (12)

Sarah Cannon Research Institute SC

Nashville, Tennessee, United States

Huntsman Cancer Institute SC

Salt Lake City, Utah, United States

Novartis Investigative Site

Salzburg, Austria

Outcomes

Primary Outcomes

Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793

Time frame: Up to 90 days after end of treatment

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 Outcomes

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).

Time frame: 48 months

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).

Time frame: 48 months

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).

Time frame: 48 months

Progression free survival (PFS)

Time frame: 48 months

Data from ClinicalTrials.gov

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