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

NCT ID: NCT02947165

Last Updated: 2022-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-25
• Study Completion Date: 2021-06-18

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NIS793

Group Type: EXPERIMENTAL

NIS793

Intervention Type: DRUG

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

NIS793 + PDR001

Group Type: EXPERIMENTAL

NIS793

Intervention Type: DRUG

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

PDR001

Intervention Type: DRUG

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

Interventions

NIS793

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

Intervention Type: DRUG

PDR001

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Sarah Cannon Research Institute SC

Nashville, Tennessee, United States

Huntsman Cancer Institute SC

Salt Lake City, Utah, United States

Novartis Investigative Site

Salzburg, , Austria

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Kashiwa, Chiba, Japan

Novartis Investigative Site

Sankt Gallen, , Switzerland

Novartis Investigative Site

Taipei, , Taiwan

Countries

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

References

Bauer TM, Santoro A, Lin CC, Garrido-Laguna I, Joerger M, Greil R, Spreafico A, Yau T, Goebeler ME, Hutter-Kronke ML, Perotti A, Juif PE, Lu D, Barys L, Cremasco V, Pelletier M, Evans H, Fabre C, Doi T. Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-beta monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors. J Immunother Cancer. 2023 Nov 29;11(11):e007353. doi: 10.1136/jitc-2023-007353.

Reference Type: DERIVED

PMID: 38030303 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30832732 (View on PubMed)

Other Identifiers

2016-003044-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CNIS793X2101

Identifier Type: -

Identifier Source: org_study_id