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

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: PDR001; Drug: LAG525

Study type: Interventional

Funder types: Industry

Identifiers

NCT02460224

CLAG525X2101C

2015-000449-21 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 490 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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490 participants in 29 patient groups

Phase 1: LAG525 1 mg/kg Q2W

Experimental group

Description:

Single-agent LAG525 1 mg/kg Q2W

Treatment:

Drug: LAG525

Phase 1: LAG525 3 mg/kg Q2W

Experimental group

Description:

Single-agent LAG525 3 mg/kg Q2W

Treatment:

Drug: LAG525

Phase 1: LAG525 5 mg/kg Q2W

Experimental group

Description:

Single-agent LAG525 5 mg/kg Q2W

Treatment:

Drug: LAG525

Phase 1: LAG525 10 mg/kg Q2W

Experimental group

Description:

Single-agent LAG525 10 mg/kg Q2W

Treatment:

Drug: LAG525

Phase 1: LAG525 15 mg/kg Q2W

Experimental group

Description:

Single-agent LAG525 15 mg/kg Q2W

Treatment:

Drug: LAG525

Phase 1: LAG525 240 mg Q2W

Experimental group

Description:

Single-agent LAG525 240 mg Q2W

Treatment:

Drug: LAG525

Phase 1: LAG525 400 mg Q2W

Experimental group

Description:

Single-agent LAG525 400 mg Q2W

Treatment:

Drug: LAG525

Phase 1: LAG525 3 mg/kg Q4W

Experimental group

Description:

Single-agent LAG525 3 mg/kg Q4W

Treatment:

Drug: LAG525

Phase 1: LAG525 5 mg/kg Q4W

Experimental group

Description:

Single-agent LAG525 5 mg/kg Q4W

Treatment:

Drug: LAG525

Phase 1: LAG525 10 mg/kg Q4W

Experimental group

Description:

Single-agent LAG525 10 mg/kg Q4W

Treatment:

Drug: LAG525

Phase 1: LAG525 400 mg Q4W

Experimental group

Description:

Single-agent LAG525 400 mg Q4W

Treatment:

Drug: LAG525

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Experimental group

Description:

Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: LAG525

Drug: PDR001

Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Experimental group

Description:

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1

Treatment:

Drug: LAG525

Drug: PDR001

Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W

Experimental group

Description:

Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1

Treatment:

Drug: LAG525

Drug: PDR001

Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Experimental group

Description:

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1

Treatment:

Drug: LAG525

Drug: PDR001