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Completed

NCT Number: NCT02947165

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

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

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Colonic Diseases Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Hepatocellular Cancer Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Liver Diseases Liver Neoplasms Lung Cancer Lung Diseases Lung Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Site Pancreatic Cancer Pancreatic Diseases Pancreatic Neoplasms Rectal Diseases Renal Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Thoracic Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Salzburg, Austria

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Written informed consent must be obtained prior to any screening procedures.
  • Patient (male or female) ≥ 18 years of age.
  • 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.
  • 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.

  • ECOG Performance Status ≤ 2.
  • 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

  • History of severe hypersensitivity reactions to study treatment ingredients or other monoclonal antibodies and components of study drug.
  • 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.
  • HIV infection.
  • Active HBV or HCV infection.

Other protocol-defined inclusion/exclusion criteria may apply.

Treatment and study plan

NIS793

Drug

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

PDR001

Drug

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

Primary outcomes

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

    Time frame: Up to 90 days after end of treatment

  2. 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

  1. Best overall response (BOR)

    Time frame: 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).

  2. Disease control rate (DCR)

    Time frame: 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).

  3. Overall response rate (ORR)

    Time frame: 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).

  4. Progression free survival (PFS)

    Time frame: 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.

  5. Duration of response (DOR)

    Time frame: 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).

  6. Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001

    Time frame: 48 months

    Evaluate serum concentration of NIS793 and PDR001 up to 8 cycles after start of treatment and at end of treatment.

  7. Presence of anti-NIS793 and anti-PDR001 antibodies

    Time frame: 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.

  8. Concentration of anti-NIS793 and anti-PDR001 antibodies

    Time frame: 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.

  9. Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.

    Time frame: 48 months

    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  10. Cmax for NIS793 single agent and NIS793 in combination with PDR001.

    Time frame: 48 months

    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  11. Tmax for NIS793 single agent and NIS793 in combination with PDR001.

    Time frame: 48 months

    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  12. Half life of NIS793 as single agent and in combination with PDR001.

    Time frame: 48 months

    Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

  13. Characterization of tumor infiltrating lymphocytes (TILs) by H&E

    Time frame: 48 months

    Assess change from baseline of immune infiltrates in tumor biopsies after 2 cycles of treatment.

  14. Characterization of tumor infiltrating lymphocytes by immunohistochemistry using markers such as CD8 and PD-L1

    Time frame: 48 months

    Assess change from baseline in immunological markers in tumor biopsies after 2 cycles of treatment.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase I/Ib, Open-label, Multi-center Dose Escalation Study of NIS793 in Combination With PDR001 in Adult Patients With Advanced Malignancies

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Oct 27, 2016
Registry last updated
Jan 31, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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