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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 : Completed
First Posted : December 7, 2017
Results First Posted : April 19, 2021
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Biological: LAG525 Phase 2

Detailed Description:

This was a phase II, open-label 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. There were 7 tumor cohorts assessed: 1) Small cell lung cancer, 2) Gastric/esophageal adenocarcinoma, 3) Castration resistant prostate adenocarcinoma (CRPC), 4) Soft tissue sarcoma, 5) Ovarian adenocarcinoma, 6) Advanced well-differentiated neuroendocrine tumors and 7) Diffuse large B cell lymphoma (DLBCL).

Participants were treated with the combination of PDR001 with LAG525 once every 3 weeks (Q3W) via intravenous (i.v.) infusion. Participants received study treatment for a maximum of 2 years, or until disease progression (assessed by investigator per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma criteria (Cheson et al 2007)), unacceptable toxicity, death or discontinuation from study treatment for any other reason.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a phase II, open-label, 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
Official Title: 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.
Actual Study Start Date : January 24, 2018
Actual Primary Completion Date : February 21, 2019
Actual Study Completion Date : September 17, 2020


Arm Intervention/treatment
Experimental: PDR001+LAG525
PDR001 and LAG525 administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
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.




Primary Outcome Measures :
  1. Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma [ Time Frame: 24 weeks ]

    Clinical Benefit Rate (CBR) is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) and Stable Disease (SD). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).

    CBR (CR+PR+SD) is reported overall and by tumor type in multiple solid tumors and lymphoma.



Secondary Outcome Measures :
  1. Overall Response Rate (ORR) up to 24 Months [ Time Frame: Baseline up to approximately 24 months ]
    Determine Overall Response (OR) of PR or 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

  2. 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.

  3. 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.

  4. 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.

  5. Progression Free Survival (PFS) up to 24 Months [ Time Frame: Baseline up to approximatley 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.

  6. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to approximately 24 months ]
    Number of participants with AEs and SAEs including changes in laboratory parameters, vital signs and ECGs

  7. Number of Participants With Dose Interruptions [ Time Frame: Baseline up to approximately 24 months ]
    Tolerability measured as the number of participants with dose interruptions.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients eligible for inclusion in this study had 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).

Exclusion Criteria:

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

  • History of severe hypersensitivity reactions to other monoclonal antibodies.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03365791


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] February 3, 2021
Study Protocol  [PDF] July 16, 2018

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03365791    
Other Study ID Numbers: CPDR001XUS01
First Posted: December 7, 2017    Key Record Dates
Results First Posted: April 19, 2021
Last Update Posted: April 19, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
PDR001
LAG525
Immune checkpoint blockade
Solid tumor malignancy
lymphoma
Small cell lung cancer (SCLC)
Gastric/esophageal adenocarcinoma
Castration resistant prostate adenocarcinoma (CRPC)
Soft tissue sarcoma
Ovarian adenocarcinoma
Advanced well-differentiated neuroendocrine tumors (NETs)
Diffuse large B cell lymphoma (DLBCL)
Additional relevant MeSH terms:
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Lymphoma
Adenocarcinoma
Neoplasms
Sarcoma
Lymphoma, B-Cell
Small Cell Lung Carcinoma
Lymphoma, Large B-Cell, Diffuse
Neuroendocrine Tumors
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Connective and Soft Tissue
Lymphoma, Non-Hodgkin
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Hematologic Diseases