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

NCT ID: NCT02460224

Last Updated: 2022-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 490 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-17
• Study Completion Date: 2020-12-31

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.

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: LAG525 1 mg/kg Q2W

Single-agent LAG525 1 mg/kg Q2W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 3 mg/kg Q2W

Single-agent LAG525 3 mg/kg Q2W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 5 mg/kg Q2W

Single-agent LAG525 5 mg/kg Q2W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 10 mg/kg Q2W

Single-agent LAG525 10 mg/kg Q2W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 15 mg/kg Q2W

Single-agent LAG525 15 mg/kg Q2W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 240 mg Q2W

Single-agent LAG525 240 mg Q2W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 400 mg Q2W

Single-agent LAG525 400 mg Q2W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 3 mg/kg Q4W

Single-agent LAG525 3 mg/kg Q4W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 5 mg/kg Q4W

Single-agent LAG525 5 mg/kg Q4W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 10 mg/kg Q4W

Single-agent LAG525 10 mg/kg Q4W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

Phase 1: LAG525 400 mg Q4W

Single-agent LAG525 400 mg Q4W

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

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)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

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

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

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

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

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

Group Type: EXPERIMENTAL

LAG525

Intervention Type: DRUG

LAG525 was administered via intravenous (i.v.) infusion

PDR001

Intervention Type: DRUG

PDR001 was administered via i.v. infusion

Interventions

LAG525

LAG525 was administered via intravenous (i.v.) infusion

Intervention Type: DRUG

PDR001

PDR001 was administered via i.v. infusion

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Columbia University Medical Center SC LAG X2101C

New York, New York, United States

Memorial Sloan Kettering Cancer Center SC

New York, New York, United States

Duke Clinical Research Institute SC

Durham, North Carolina, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Cancer Therapy and Research Center UT Health Science Center CTRC 2

San Antonio, Texas, United States

Huntsman Cancer Institute Huntsman Cancer Institute

Salt Lake City, Utah, United States

Novartis Investigative Site

Westmead, New South Wales, Australia

Novartis Investigative Site

Heidelberg, Victoria, Australia

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Edmonton, Alberta, Canada

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Lyon, , France

Novartis Investigative Site

Saint-Herblain Cédex, , France

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Modena, MO, Italy

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Taipei, , Taiwan

Countries

United States; Australia; Belgium; Canada; France; Germany; Hong Kong; Italy; Japan; Singapore; Spain; Taiwan

References

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.

Reference Type: DERIVED

PMID: 38336861 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35217575 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000449-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLAG525X2101C

Identifier Type: -

Identifier Source: org_study_id