Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.
A Phase I/II, Open Label, Multicenter Study of the Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 Administered to Patients With Advanced Malignancies
2 other identifiers
interventional
490
12 countries
24
Brief Summary
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. The study consists of a dose escalation (phase 1) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for LAG525 as a single agent and in combination with PDR001, and a dose expansion (phase 2) which characterized treatment of LAG525 in combination with PDR001 at the MTD or RP2D.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2015
Longer than P75 for phase_1
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 9, 2015
CompletedFirst Posted
Study publicly available on registry
June 2, 2015
CompletedStudy Start
First participant enrolled
June 17, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2020
CompletedResults Posted
Study results publicly available
February 10, 2022
CompletedFebruary 10, 2022
January 1, 2022
5.5 years
May 9, 2015
December 10, 2021
January 17, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with single-agent LAG525 or within the first two cycles of treatment with the combination of LAG525 and PDR001. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
15 days for single-agent LAG525 arms and 30 days for the combination LAG525 + PDR001 arms
Phase 2: Overall Response Rate (ORR) Per RECIST 1.1
Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). 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 diameters of all target lesions, taking as reference the baseline sum of diameters. ORR is reported by tumor type.
From start of treatment until end of treatment, assessed up to 2.6 years
Secondary Outcomes (41)
Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 4.5 years.
Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 2.7 years.
Phase 1: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001
From start of treatment until end of treatment, assessed up to 4.4 years.
Phase 2: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001
From start of treatment until end of treatment, assessed up to 2.6 years.
Phase 1: Relative Dose Intensity (RDI) of LAG525 and PDR001
From start of treatment until end of treatment, assessed up to 4.4 years.
- +36 more secondary outcomes
Study Arms (29)
Phase 1: LAG525 1 mg/kg Q2W
EXPERIMENTALSingle-agent LAG525 1 mg/kg Q2W
Phase 1: LAG525 3 mg/kg Q2W
EXPERIMENTALSingle-agent LAG525 3 mg/kg Q2W
Phase 1: LAG525 5 mg/kg Q2W
EXPERIMENTALSingle-agent LAG525 5 mg/kg Q2W
Phase 1: LAG525 10 mg/kg Q2W
EXPERIMENTALSingle-agent LAG525 10 mg/kg Q2W
Phase 1: LAG525 15 mg/kg Q2W
EXPERIMENTALSingle-agent LAG525 15 mg/kg Q2W
Phase 1: LAG525 240 mg Q2W
EXPERIMENTALSingle-agent LAG525 240 mg Q2W
Phase 1: LAG525 400 mg Q2W
EXPERIMENTALSingle-agent LAG525 400 mg Q2W
Phase 1: LAG525 3 mg/kg Q4W
EXPERIMENTALSingle-agent LAG525 3 mg/kg Q4W
Phase 1: LAG525 5 mg/kg Q4W
EXPERIMENTALSingle-agent LAG525 5 mg/kg Q4W
Phase 1: LAG525 10 mg/kg Q4W
EXPERIMENTALSingle-agent LAG525 10 mg/kg Q4W
Phase 1: LAG525 400 mg Q4W
EXPERIMENTALSingle-agent LAG525 400 mg Q4W
Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W
EXPERIMENTALCombination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)
Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W
EXPERIMENTALCombination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)
Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W
EXPERIMENTALCombination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)
Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W
EXPERIMENTALCombination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)
Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W
EXPERIMENTALCombination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)
Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W
EXPERIMENTALCombination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)
Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W
EXPERIMENTALCombination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)
Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W
EXPERIMENTALCombination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)
Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W
EXPERIMENTALCombination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)
Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W
EXPERIMENTALCombination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)
Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W
EXPERIMENTALCombination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)
Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W
EXPERIMENTALCombination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)
Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W
EXPERIMENTALCombination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)
Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W
EXPERIMENTALCombination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)
Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
EXPERIMENTALCombination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)
Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W
EXPERIMENTALCombination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1
Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W
EXPERIMENTALCombination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1
Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
EXPERIMENTALCombination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1
Interventions
LAG525 was administered via intravenous (i.v.) infusion
PDR001 was administered via i.v. infusion
Eligibility Criteria
You may qualify if:
- Phase I part:
- \- 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
- Phase II part:
- Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have had disease progression following their last prior therapy and fit into one of the following groups:
- Group 1: NSCLC
- Group 2: Melanoma
- Group 3: Renal cancer
- Group 4: Mesothelioma
- Group 5: TNBC
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy.
You may not qualify if:
- History of severe hypersensitivity reactions to study treatment ingredients or other mAbs
- Active, known or suspected autoimmune disease
- Active infection requiring systemic antibiotic therapy
- HIV infection. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Patients receiving chronic treatment with systemic steroid therapy, other than replacement-dose corticosteroids in the setting of adrenal insufficiency
- Patients receiving systemic treatment with any immunosuppressive medication
- Use of live vaccines against infectious disease within 4 weeks of initiation of study treatment
- Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment.
- Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy or increasing doses of corticosteroids within the prior 2 weeks
- History of drug-induced pneumonitis or current pneumonitis.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Columbia University Medical Center SC LAG X2101C
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center SC
New York, New York, 10065, United States
Duke Clinical Research Institute SC
Durham, North Carolina, 27704, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Cancer Therapy and Research Center UT Health Science Center CTRC 2
San Antonio, Texas, 78229, United States
Huntsman Cancer Institute Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Novartis Investigative Site
Westmead, New South Wales, 2145, Australia
Novartis Investigative Site
Heidelberg, Victoria, 3084, Australia
Novartis Investigative Site
Leuven, 3000, Belgium
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2, Canada
Novartis Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Novartis Investigative Site
Lyon, 69373, France
Novartis Investigative Site
Saint-Herblain Cédex, 44805, France
Novartis Investigative Site
Heidelberg, 69120, Germany
Novartis Investigative Site
Würzburg, 97080, Germany
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Modena, MO, 41124, Italy
Novartis Investigative Site
Fukuoka, Fukuoka, 811-1395, Japan
Novartis Investigative Site
Singapore, 119228, Singapore
Novartis Investigative Site
Singapore, 169610, Singapore
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
Madrid, 28009, Spain
Novartis Investigative Site
Taipei, 10002, Taiwan
Related Publications (2)
Rivoltini L, Camisaschi C, Fuca G, Paolini B, Vergani B, Beretta V, Damian S, Duca M, Cresta S, Magni M, Leone BE, Castelli C, de Braud F, De Santis F, Di Nicola M. Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade. Sci Rep. 2024 Feb 9;14(1):3379. doi: 10.1038/s41598-024-54041-9.
PMID: 38336861DERIVEDSchoffski P, Tan DSW, Martin M, Ochoa-de-Olza M, Sarantopoulos J, Carvajal RD, Kyi C, Esaki T, Prawira A, Akerley W, De Braud F, Hui R, Zhang T, Soo RA, Maur M, Weickhardt A, Krauss J, Deschler-Baier B, Lau A, Samant TS, Longmire T, Chowdhury NR, Sabatos-Peyton CA, Patel N, Ramesh R, Hu T, Carion A, Gusenleitner D, Yerramilli-Rao P, Askoxylakis V, Kwak EL, Hong DS. Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) +/- anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies. J Immunother Cancer. 2022 Feb;10(2):e003776. doi: 10.1136/jitc-2021-003776.
PMID: 35217575DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 9, 2015
First Posted
June 2, 2015
Study Start
June 17, 2015
Primary Completion
December 31, 2020
Study Completion
December 31, 2020
Last Updated
February 10, 2022
Results First Posted
February 10, 2022
Record last verified: 2022-01