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PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

Primary Purpose

Small Cell Lung Cancer, Gastric Adenocarcinoma, Esophageal Adenocarcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PDR001
LAG525
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • California Pacific Medical Center Drug Shipment (2)
  • Hematology Oncology Associates of the Treasure Coast
  • University Cancer and Blood Center, LLC
  • Northwestern University Medical School
  • University of Illinois Cancer Center at Chicago SC
  • Illinois Cancer Care P.C. Jesse Brown VA
  • Indiana University
  • University of Iowa Hospitals and Clinics Comprehensive Cancer Center
  • The University of Kansas Clinical Research Center
  • Weinberg Cancer Institute at Franklin Square Hospital
  • Billings Clinic Dept of Billings Clinic(2)
  • Oncology Hematology West Nebraska Cancer Specialists
  • Comprehensive Cancer Centers
  • Oregon Health and Science University
  • Oncology Consultants Oncology Consultants
  • University of Texas - MD Anderson Cancer Center
  • Kadlec Clinic Hematology and Oncology
  • Providence Regional Cancer System SC
  • University of Wisconsin Hospital and Clinics
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PDR001+LAG525

Arm Description

PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.

Outcomes

Primary Outcome Measures

Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma
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). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. CBR (CR+PR+SD) is reported overall and by tumor type.

Secondary Outcome Measures

Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). 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). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. ORR (CR+PR) is reported overall (including all tumor types).
Time to Response (TTR)
TTR is defined as the time from the date of first dose to the date of first documented response of Complete Response (CR) or Partial Response (PR). In case of solid tumor if a patient did not achieve a confirmed response they were censored at maximum follow-up for patients who had a PFS event (progressed or died due to any cause), or at last adequate tumor assessment date otherwise. 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).
Duration of Response (DOR)
DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented progression/relapse or death due to any cause within 150 days of the last study drug dose date. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. 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).
Time to Progression (TTP)
TTP is the time from start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient not had an event, time to progression was censored at the date of last adequate tumor assessment. 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).
Progression-Free Survival (PFS)
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 150 days of the last dose. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. 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).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs including changes in laboratory parameters, vital signs and ECGs qualifying and reported as AEs.
Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug
Number of participants with at least one dose interruption of PDR001 and LAG525 and number of participants with permanent dose discontinuation of PDR001 and LAG525.
Dose Intensity
Dose intensity (mg/day) of PDR001 and LAG525 is calculated as cumulative dose in milligrams divided by duration of exposure in days.

Full Information

First Posted
November 20, 2017
Last Updated
May 4, 2022
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03365791
Brief Title
PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies
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.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
January 24, 2018 (Actual)
Primary Completion Date
February 21, 2019 (Actual)
Study Completion Date
September 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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 300 mg with LAG525 400 mg 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PDR001+LAG525
Arm Type
Experimental
Arm Description
PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Intervention Type
Biological
Intervention Name(s)
PDR001
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
LAG525
Intervention Description
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 Measure Information:
Title
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma
Description
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). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. CBR (CR+PR+SD) is reported overall and by tumor type.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). 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). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. ORR (CR+PR) is reported overall (including all tumor types).
Time Frame
From start of treatment until end of treatment, assessed up to 113 weeks
Title
Time to Response (TTR)
Description
TTR is defined as the time from the date of first dose to the date of first documented response of Complete Response (CR) or Partial Response (PR). In case of solid tumor if a patient did not achieve a confirmed response they were censored at maximum follow-up for patients who had a PFS event (progressed or died due to any cause), or at last adequate tumor assessment date otherwise. 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).
Time Frame
From start of treatment to the first documented response of either complete response or partial response, assessed up to 113 weeks
Title
Duration of Response (DOR)
Description
DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented progression/relapse or death due to any cause within 150 days of the last study drug dose date. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. 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).
Time Frame
From first documented response (CR or PR) to first documented progression or death, assessed up to 113 weeks
Title
Time to Progression (TTP)
Description
TTP is the time from start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient not had an event, time to progression was censored at the date of last adequate tumor assessment. 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).
Time Frame
From start of treatment to first documented progression or death due to underlying cancer, assessed up to 113 weeks
Title
Progression-Free Survival (PFS)
Description
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 150 days of the last dose. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. 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).
Time Frame
From start of treatment to first documented progression or death, assessed up to 113 weeks
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Number of participants with AEs and SAEs including changes in laboratory parameters, vital signs and ECGs qualifying and reported as AEs.
Time Frame
From first dose of study treatment until last dose of study treatment plus 150 days post treatment, assessed up to 135 weeks.
Title
Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug
Description
Number of participants with at least one dose interruption of PDR001 and LAG525 and number of participants with permanent dose discontinuation of PDR001 and LAG525.
Time Frame
From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.
Title
Dose Intensity
Description
Dose intensity (mg/day) of PDR001 and LAG525 is calculated as cumulative dose in milligrams divided by duration of exposure in days.
Time Frame
From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
California Pacific Medical Center Drug Shipment (2)
City
San Francisco
State/Province
California
ZIP/Postal Code
94120-7999
Country
United States
Facility Name
Hematology Oncology Associates of the Treasure Coast
City
Port Saint Lucie
State/Province
Florida
ZIP/Postal Code
34952
Country
United States
Facility Name
University Cancer and Blood Center, LLC
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Northwestern University Medical School
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Illinois Cancer Center at Chicago SC
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Illinois Cancer Care P.C. Jesse Brown VA
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615-7828
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Hospitals and Clinics Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
The University of Kansas Clinical Research Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Weinberg Cancer Institute at Franklin Square Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237-3998
Country
United States
Facility Name
Billings Clinic Dept of Billings Clinic(2)
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Oncology Hematology West Nebraska Cancer Specialists
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68124
Country
United States
Facility Name
Comprehensive Cancer Centers
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Oncology Consultants Oncology Consultants
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Kadlec Clinic Hematology and Oncology
City
Kennewick
State/Province
Washington
ZIP/Postal Code
99336
Country
United States
Facility Name
Providence Regional Cancer System SC
City
Lacey
State/Province
Washington
ZIP/Postal Code
98503
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=974
Description
A Plain Language Trial Summary is available on novctrd.com

Learn more about this trial

PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

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