Clinical trial NCT03365791: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-12-07
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma
timeFrame: 24 weeks
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From start of treatment until end of treatment, assessed up to 113 weeks
measure: Time to Response (TTR)
timeFrame: From start of treatment to the first documented response of either complete response or partial response, assessed up to 113 weeks
measure: Duration of Response (DOR)
timeFrame: From first documented response (CR or PR) to first documented progression or death, assessed up to 113 weeks
measure: Time to Progression (TTP)
timeFrame: From start of treatment to first documented progression or death due to underlying cancer, assessed up to 113 weeks
measure: Progression-Free Survival (PFS)
timeFrame: From start of treatment to first documented progression or death, assessed up to 113 weeks
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study treatment until last dose of study treatment plus 150 days post treatment, assessed up to 135 weeks.
measure: Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug
timeFrame: From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.
measure: Dose Intensity
timeFrame: From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: California Pacific Medical Center Drug Shipment (2)
state: California
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Athens
country: United States
facility: University Cancer and Blood Center, LLC
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Cancer Center at Chicago SC
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care P.C. Jesse Brown VA
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics Comprehensive Cancer Center
state: Iowa
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Baltimore
country: United States
facility: Weinberg Cancer Institute at Franklin Square Hospital
state: Maryland
city: Billings
country: United States
facility: Billings Clinic Dept of Billings Clinic(2)
state: Montana
city: Omaha
country: United States
facility: Oncology Hematology West Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers
state: Nevada
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: Oncology Consultants Oncology Consultants
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Lacey
country: United States
facility: Providence Regional Cancer System SC
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: