Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.

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ClinicalTrials.gov Identifier: NCT02460224

Recruitment Status : Completed

First Posted : June 2, 2015

Results First Posted : February 10, 2022

Last Update Posted : February 10, 2022

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Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Drug: LAG525 Drug: PDR001	Phase 1 Phase 2

Detailed Description:

This was a Phase 1/2, multi-center, open-label study comprising a Phase 1 dose escalation part followed by a Phase 2 dose expansion part.

During the Phase 1 dose escalation part patients with any advanced solid tumor received the study treatment until the MTD was reached or a lower RP2D was established. The study had the following 3 dose escalation parts: 1) Single-agent LAG525; 2) Single-agent LAG525 in Japanese patients; 3) Combination of LAG525 with PDR001.

Once the RP2D or MTD had been determined in the escalation parts, additional patients were to be enrolled in the Phase 2 expansion parts in order to assess the preliminary anti-tumor activity. Phase 2 expansion cohorts testing single-agent LAG525 were not opened for enrollment based on emerging data including but not limited to preliminary anti-tumor activity. Phase 2 expansion cohorts for the combination of LAG525 with PDR001 were opened and 5 tumor types were assessed: 1) Non-small cell lung cancer (NSCLC); 2) Melanoma; 3) Renal cell cancer (RCC); 4) Mesothelioma; 5) Triple negative breast cancer (TNBC). The efficacy and safety of the combination of LAG525 with PDR001 in these tumor types was assessed in both the PD-1/PD-L1 pre-treated and naïve settings.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	490 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	June 17, 2015
Actual Primary Completion Date :	December 31, 2020
Actual Study Completion Date :	December 31, 2020

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Renal Cell Carcinoma Malignant Mesothelioma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1: LAG525 1 mg/kg Q2W Single-agent LAG525 1 mg/kg Q2W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 3 mg/kg Q2W Single-agent LAG525 3 mg/kg Q2W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 5 mg/kg Q2W Single-agent LAG525 5 mg/kg Q2W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 10 mg/kg Q2W Single-agent LAG525 10 mg/kg Q2W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 15 mg/kg Q2W Single-agent LAG525 15 mg/kg Q2W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 240 mg Q2W Single-agent LAG525 240 mg Q2W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 400 mg Q2W Single-agent LAG525 400 mg Q2W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 3 mg/kg Q4W Single-agent LAG525 3 mg/kg Q4W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 5 mg/kg Q4W Single-agent LAG525 5 mg/kg Q4W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 10 mg/kg Q4W Single-agent LAG525 10 mg/kg Q4W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 400 mg Q4W Single-agent LAG525 400 mg Q4W	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion
Experimental: Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion
Experimental: Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1	Drug: LAG525 LAG525 was administered via intravenous (i.v.) infusion Drug: PDR001 PDR001 was administered via i.v. infusion

Outcome Measures

Primary Outcome Measures :

Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: 15 days for single-agent LAG525 arms and 30 days for the combination LAG525 + PDR001 arms ]
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.
Phase 2: Overall Response Rate (ORR) Per RECIST 1.1 [ Time Frame: From start of treatment until end of treatment, assessed up to 2.6 years ]
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.

Secondary Outcome Measures :

Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 4.5 years. ]
Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The number of participants in each category (Rest of the World (ROW) patients, Japanese patients) with AEs and SAEs are reported in this record.
Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 2.7 years. ]
Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The number of participants with AEs and SAEs is reported for each tumor type.
Phase 1: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001 [ Time Frame: From start of treatment until end of treatment, assessed up to 4.4 years. ]
Number of participants with at least one dose reduction of LAG525, at least one dose interruption of LAG525, at least one dose reduction of PDR001 and at least one dose interruption of PDR001.

Japanese patients were not treated with PDR001 and therefore the dose reductions and dose interruptions of this study drug are not applicable.
Phase 2: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001 [ Time Frame: From start of treatment until end of treatment, assessed up to 2.6 years. ]
Number of participants with at least one dose reduction of LAG525, at least one dose interruption of LAG525, at least one dose reduction of PDR001 and at least one dose interruption of PDR001.

The number of participants with dose reductions and dose interruptions of both study drugs is reported for each tumor type.
Phase 1: Relative Dose Intensity (RDI) of LAG525 and PDR001 [ Time Frame: From start of treatment until end of treatment, assessed up to 4.4 years. ]
Relative dose intensity of each study drug is calculated with the following formula: 100 x actual dose intensity (mg/day)/planned dose intensity (mg/day).

Japanese patients were not treated with PDR001 and therefore the RDI of this study drug is not applicable.
Phase 2: Relative Dose Intensity (RDI) of LAG525 and PDR001 [ Time Frame: From start of treatment until end of treatment, assessed up to 2.6 years. ]
Relative dose intensity of each study drug is calculated with the following formula: 100 x actual dose intensity (mg/day)/planned dose intensity (mg/day).

The RDI of both study drugs is reported for each tumor type.
Phase 1: Maximum Observed Serum Concentration (Cmax) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Phase 2: Maximum Observed Serum Concentration (Cmax) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.
Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.
Phase 1: Terminal Elimination Half-life (T1/2) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Phase 2: Terminal Elimination Half-life (T1/2) of LAG525 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Phase 1: Maximum Observed Serum Concentration (Cmax) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.

Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Phase 2: Maximum Observed Serum Concentration (Cmax) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.

Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.

Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.
Phase 1: Terminal Elimination Half-life (T1/2) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.

Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Phase 2: Terminal Elimination Half-life (T1/2) of PDR001 [ Time Frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W). ]
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Phase 1: Number of Participants With Anti-LAG525 Antibodies [ Time Frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years). ]
Validated immunoassays were used for screening and confirmation of the presence of anti-LAG525 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Phase 2: Number of Participants With Anti-LAG525 Antibodies [ Time Frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years). ]
Validated immunoassays were used for screening and confirmation of the presence of anti-LAG525 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Phase 1: Number of Participants With Anti-PDR001 Antibodies [ Time Frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years). ]
Validated immunoassays were used for screening and confirmation of the presence of anti-PDR001 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Phase 2: Number of Participants With Anti-PDR001 Antibodies [ Time Frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years). ]
Validated immunoassays were used for screening and confirmation of the presence of anti-PDR001 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Phase 1: Overall Response Rate (ORR) Per RECIST 1.1 [ Time Frame: From start of treatment until end of treatment, assessed up to 4.4 years ]
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 for ROW and Japanese patients.
Phase 1: Overall Response Rate (ORR) Per irRC [ Time Frame: From start of treatment until end of treatment, assessed up to 4.4 years ]
TTumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). ORR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR) or immune related Partial Response (irPR).

For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters.

ORR is reported for ROW and Japanese patients.
Phase 2: Overall Response Rate (ORR) Per irRC [ Time Frame: From start of treatment until end of treatment, assessed up to 2.6 years ]
Tumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). ORR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR) or immune related Partial Response (irPR).

For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters.

ORR is reported by tumor type.
Phase 1: Disease Control Rate (DCR) Per RECIST 1.1 [ Time Frame: From start of treatment until end of treatment, assessed up to 4.4 years ]
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). DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD).

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; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.

DCR is reported for ROW and Japanese patients.
Phase 1: Disease Control Rate (DCR) Per irRC [ Time Frame: From start of treatment until end of treatment, assessed up to 4.4 years ]
Tumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). DCR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR), immune related Partial Response (irPR) or immune related Stable Disease (irSD).

For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for irPR or irCR nor an increase in lesions which would qualify for progression.

DCR is reported for ROW and Japanese patients.
Phase 2: Disease Control Rate (DCR) Per RECIST 1.1 [ Time Frame: From start of treatment until end of treatment, assessed up to 2.6 years ]
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). DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD).

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; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.

DCR is reported by tumor type.
Phase 2: Disease Control Rate (DCR) Per irRC [ Time Frame: From start of treatment until end of treatment, assessed up to 2.6 years ]
Tumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). DCR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR), immune related Partial Response (irPR) or immune related Stable Disease (irSD).

For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for irPR or irCR nor an increase in lesions which would qualify for progression.

DCR is reported by tumor type.
Phase 1: Duration of Response (DOR) Per RECIST 1.1 [ Time Frame: From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 4.4 years ]
DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to study indication. 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 and the assessment criteria was RECIST 1.1.
Phase 1: Duration of Response (DOR) Per irRC [ Time Frame: From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 4.4 years ]
DOR only applies to subjects for whom best overall response is immune related complete response (irCR) or immune related partial response (irPR). DOR is defined as the time from the date of first documented response (irCR or irPR) to the date of first documented progression or death due to study indication. 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 and the assessment criteria was irRC.
Phase 2: Duration of Response (DOR) Per RECIST 1.1 [ Time Frame: From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 2.6 years ]
DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to study indication. 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 and the assessment criteria was RECIST 1.1.

DOR is reported by tumor type.
Phase 2: Duration of Response (DOR) Per irRC [ Time Frame: From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 2.6 years ]
DOR only applies to subjects for whom best overall response is immune related complete response (irCR) or immune related partial response (irPR). DOR is defined as the time from the date of first documented response (irCR or irPR) to the date of first documented progression or death due to study indication. 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 and the assessment criteria was irRC.

DOR is reported by tumor type.
Phase 1: Progression-free Survival (PFS) Per RECIST 1.1 [ Time Frame: From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years ]
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. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1.

PFS is reported for ROW and Japanese patients.
Phase 1: Progression-free Survival (PFS) Per irRC [ Time Frame: From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years ]
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. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

Tumor response was based on local investigator assessment and the assessment criteria was irRC.

PFS is reported for ROW and Japanese patients.
Phase 2: Progression-free Survival (PFS) Per RECIST 1.1 [ Time Frame: From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years ]
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. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1.

PFS is reported by tumor type.
Phase 2: Progression-free Survival (PFS) Per irRC [ Time Frame: From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years ]
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. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

Tumor response was based on local investigator assessment and the assessment criteria was irRC.

PFS is reported by tumor type.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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:

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.

Exclusion Criteria:

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.

Contacts and Locations

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): NCT02460224

Locations

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United States, New York
Columbia University Medical Center SC LAG X2101C
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center SC
New York, New York, United States, 10065
United States, North Carolina
Duke Clinical Research Institute SC
Durham, North Carolina, United States, 27704
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Cancer Therapy and Research Center UT Health Science Center CTRC 2
San Antonio, Texas, United States, 78229
United States, Utah
Huntsman Cancer Institute Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Australia, New South Wales
Novartis Investigative Site
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Novartis Investigative Site
Heidelberg, Victoria, Australia, 3084
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Alberta
Novartis Investigative Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
France
Novartis Investigative Site
Lyon Cedex, France, 69373
Novartis Investigative Site
Saint-Herblain Cédex, France, 44805
Germany
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Wuerzburg, Germany, 97080
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Italy
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Modena, MO, Italy, 41124
Japan
Novartis Investigative Site
Fukuoka-city, Fukuoka, Japan, 811-1395
Singapore
Novartis Investigative Site
Singapore, Singapore, 119228
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Madrid, Spain, 28009
Taiwan
Novartis Investigative Site
Taipei, Taiwan, 10002

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 ):

Study Protocol [PDF] June 27, 2019

Statistical Analysis Plan [PDF] March 15, 2021

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schoffski 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.

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Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02460224
Other Study ID Numbers:	CLAG525X2101C 2015-000449-21 ( EudraCT Number )
First Posted:	June 2, 2015 Key Record Dates
Results First Posted:	February 10, 2022
Last Update Posted:	February 10, 2022
Last Verified:	January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided
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 ):


Non-small cell lung cancer Melanoma Renal cancer Mesothelioma	Triple Negative Breast TNBC Renal

Additional relevant MeSH terms:

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Neoplasms Spartalizumab Immune Checkpoint Inhibitors	Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents

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