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PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT03365791
Recruitment Status : Recruiting
First Posted : December 7, 2017
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

November 20, 2017
December 7, 2017
July 3, 2018
January 24, 2018
January 30, 2020   (Final data collection date for primary outcome measure)
  • Clinical Benefit Rate (CBR) at 24 weeks of PDR001+LAG525 by tumor type in multiple solid and lymphoma [ Time Frame: At week 24 ]
    The primary objective is to assess clinical benefit rate after 24 weeks of treatment with PDR001+LAG525 based on local investigator assessment. For patients with solid tumors the assessment criteria will be RECIST 1.1 and will include responses of CR or PR or SD. For lymphoma, assessment criteria will be the Revised Response Criteria for Malignant Lymphoma, (Cheson et al 2007).There is only one hypothesis to be tested, only one primary outcome measurement, independent of the underlying disease (solid tumor or lymphoma): Is the observed Clinical Benefit Rate (CBR) in this trial better than the historical CBR (from the literature)? These are all absolute numbers for each cohort, reported together and independent of how they were measured.
  • Progression free survival (PFS) up to 24 months [ Time Frame: Baseline up to approximately 24 months ]
    Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.
Same as current
Complete list of historical versions of study NCT03365791 on ClinicalTrials.gov Archive Site
  • Overall Response Rate (ORR) up to 24 months [ Time Frame: Baseline up to approximately 24 months ]
    Determine Overall Response (OR) of Partial Response (PR) or Complete Response (CR) based on local investigator assessment utilizing RECIST 1.1 in solid tumors and by Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007) in lymphoma
  • Time to response (TTR) up to 24 months [ Time Frame: Baseline up to approximately 24 months. ]
    Time to response (TTR) is defined as the time from the date of first dose to the date of first documented response of CR or PR.
  • Safety and tolerability [ Time Frame: Baseline up to approximately 24 months ]
    Safety incidence and severity of adverse events (AEs) and serious adverse events (SAEs) including changes in laboratory parameters, vital signs and ECGs considered to be clinically significant
  • Duration of response (DOR) up to 24 months [ Time Frame: First documented response to progression up to approximately 24 months ]
    The duration of response (DOR) applies only to patients whose best response was PR or CR. The duration of response is defined as the time from the first documented response to the date first documented disease progression or relapse or death due to any cause. The duration of response will be summarized descriptively for each patient group.
  • Time to progression (TTP) up to 24 months [ Time Frame: Baseline up to approximately 24 months ]
    Time to progression (TTP) is defined as the time from the date of first dose to the date of first documented disease progression or relapse.
Same as current
Not Provided
Not Provided
 
PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies
Modular Phase 2 Study to Link Combination Immune-therapy to Patients With Advanced Solid and Hematologic Malignancies. Module 9: PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies.
The purpose of this signal seeking study is to determine whether treatment with PDR001 and LAG525 demonstrates sufficient efficacy in advanced malignancies to warrant further study.
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a phase II, open-label, parallel-cohort study to determine the efficacy and safety of treatment with the combination of PDR001+LAG525 across multiple tumor types that are relapsed and/or refractory to available standard of care therapies. Patients will receive study treatment for a maximum of 2 years, All disease assessments will be performed locally by the investigator.
Masking: None (Open Label)
Primary Purpose: Treatment
  • Small Cell Lung Cancer
  • Gastric Adenocarcinoma
  • Esophageal Adenocarcinoma
  • Castration Resistant Prostate Adenocarcinoma
  • Soft Tissue Sarcoma
  • Ovarian Adenocarcinoma
  • Advanced Well-differentiated Neuroendocrine Tumors
  • Diffuse Large B Cell Lymphoma
  • Biological: PDR001
    PDR001 is a high-affinity, ligand-blocking, humanized anti-programmed death-1 (PD-1) IgG4 antibody that blocks the binding of Programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) to PD-1.
  • Biological: LAG525
    LAG525 is a high-affinity, ligand-blocking, humanized anti-LAG-3 IgG4 antibody which blocks the binding of the known LAG-3 ligand MHC class II to LAG-3.
Experimental: PDR001 and LAG525
PDR001 will be supplied as powder for solution for infusion. LAG525 will be supplied as a liquid formulation. PDR001 and LAG525 will be administered via i.v. infusion over 30 minutes once every 3 weeks. LAG525 will be given first followed by PDR001.
Interventions:
  • Biological: PDR001
  • Biological: LAG525
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
Same as current
February 1, 2021
January 30, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Patients eligible for inclusion in this study have to meet all of the following criteria:

  • Patient must have had at least one prior line of therapy for their disease and must not be beyond 4th progression/relapse of disease (5 maximum prior lines).
  • Patient has a pathology confirmed diagnosis of a solid tumor or lymphoma listed in the section "condition". Patients must have measurable disease as per appropriate guidelines (Solid Tumors by RECIST 1.1 and Diffuse Large B-cell Lymphoma by Revised Response Criteria for Malignant Lymphoma - Cheson et al 2007).
  • Expansion Cohorts only: Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Exceptions may be considered after discussion with the sponsor.

Exclusion Criteria:

Patients eligible for this study must not meet any of the following criteria:

  • History of severe hypersensitivity reactions to other mAbs.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Active, known or suspected autoimmune disease or a documented history of autoimmune disease within three years prior to screening with a few exceptions as per protocol.
  • Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
  • Patient with second primary malignancy within < 3 years of first dose of study treatment.
  • Prior immunotherapy treatment with PD-1, PD-L1, CTLA-4, or LAG-3 antibodies.

Other protocol-defined inclusion/exclusion criteria may apply.

Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals
United States
 
 
NCT03365791
CPDR001XUS01
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP