Phase 2
Completed N=490
Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.
Source: ClinicalTrials.gov NCT02460224 ↗Enrolled (actual)
490
Serious AEs
42.4%
Results posted
Feb 2022
Primary outcomePrimary: Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) — 1; 0; 2; 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) |
1; 0; 2; 0; 0; 0 | — |
| PRIMARY Phase 2: Overall Response Rate (ORR) Per RECIST 1.1 |
15.0; 0; 15.0; 9.1; 26.3; 5.3 | — |
| SECONDARY Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
13; 11; 6; 6; 6; 24 | — |
| SECONDARY Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
19; 22; 13; 7; 19; 22 | — |
| SECONDARY Phase 1: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Phase 2: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001 |
0; 0; 3; 3; 0; 0 | — |
| SECONDARY Phase 1: Relative Dose Intensity (RDI) of LAG525 and PDR001 |
98.9; 100; 94.4; 100; 98.2; 99.0 | — |
| SECONDARY Phase 2: Relative Dose Intensity (RDI) of LAG525 and PDR001 |
100; 100; 100; 99.8; 99.4; 99.7 | — |
| SECONDARY Phase 1: Maximum Observed Serum Concentration (Cmax) of LAG525 |
21.8; 72.4; 117; 247; 393; 73.8 | — |
| SECONDARY Phase 2: Maximum Observed Serum Concentration (Cmax) of LAG525 |
154; 106; 169; 137; 115; 102 | — |
| SECONDARY Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of LAG525 |
1.73; 1.6; 1.63; 1.63; 1.99; 1.59 | — |
| SECONDARY Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of LAG525 |
1.53; 1.55; 1.55; 1.58; 1.51; 1.53 | — |
| SECONDARY Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525 |
136; 506; 758; 1830; 2810; 500 | — |
| SECONDARY Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525 |
1260; 955; 1500; 1260; 1030; 953 | — |
| SECONDARY Phase 1: Terminal Elimination Half-life (T1/2) of LAG525 |
7.65; 11.1; 9.99; 12; 12.8; 10.3 | — |
| SECONDARY Phase 2: Terminal Elimination Half-life (T1/2) of LAG525 |
11.6; 13.3; 16.3; 15.9; 15.6; 15.5 | — |
| SECONDARY Phase 1: Maximum Observed Serum Concentration (Cmax) of PDR001 |
19.6; 19.6; 17.7; 58.8; 67.9; 76.2 | — |
| SECONDARY Phase 2: Maximum Observed Serum Concentration (Cmax) of PDR001 |
102; 68.9; 118; 100; 75.7; 71.3 | — |
| SECONDARY Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 |
1.5; 1.5; 1.55; 1.63; 1.51; 1.53 | — |
| SECONDARY Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 |
1.57; 1.57; 1.57; 1.58; 1.55; 1.53 | — |
| SECONDARY Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001 |
114; 141; 134; 437; 466; 601 | — |
| SECONDARY Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001 |
853; 629; 1020; 881; 663; 633 | — |
| SECONDARY Phase 1: Terminal Elimination Half-life (T1/2) of PDR001 |
9.71; 10.2; 12.5; 20.7; 30.8; 22.8 | — |
| SECONDARY Phase 2: Terminal Elimination Half-life (T1/2) of PDR001 |
17.2; 15.8; 16.8; 24.5; 29.1; 20 | — |
| SECONDARY Phase 1: Number of Participants With Anti-LAG525 Antibodies |
14; 10; 4; 5; 5; 19 | — |
| SECONDARY Phase 2: Number of Participants With Anti-LAG525 Antibodies |
19; 19; 4; 2; 15; 19 | — |
| SECONDARY Phase 1: Number of Participants With Anti-PDR001 Antibodies |
5; 6; 5; 4; 5; 14 | — |
| SECONDARY Phase 2: Number of Participants With Anti-PDR001 Antibodies |
18; 21; 6; 4; 16; 19 | — |
| SECONDARY Phase 1: Overall Response Rate (ORR) Per RECIST 1.1 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Phase 1: Overall Response Rate (ORR) Per irRC |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Phase 2: Overall Response Rate (ORR) Per irRC |
15.0; 0; 15.0; 9.1; 26.3; 5.3 | — |
| SECONDARY Phase 1: Disease Control Rate (DCR) Per RECIST 1.1 |
23.1; 41.7; 16.7; 0; 66.7; 24.0 | — |
| SECONDARY Phase 1: Disease Control Rate (DCR) Per irRC |
30.8; 33.3; 16.7; 0; 50.0; 28.0 | — |
| SECONDARY Phase 2: Disease Control Rate (DCR) Per RECIST 1.1 |
50.0; 50.0; 45.0; 40.9; 63.2; 42.1 | — |
| SECONDARY Phase 2: Disease Control Rate (DCR) Per irRC |
60.0; 50.0; 55.0; 40.9; 68.4; 42.1 | — |
| SECONDARY Phase 1: Duration of Response (DOR) Per RECIST 1.1 |
NA; NA; 12.2; NA; 18.4; 6.5 | — |
| SECONDARY Phase 1: Duration of Response (DOR) Per irRC |
NA; NA; 12.2; NA; NA; 9.2 | — |
| SECONDARY Phase 2: Duration of Response (DOR) Per RECIST 1.1 |
5.0; 11.0; NA; NA; NA; NA | — |
| SECONDARY Phase 2: Duration of Response (DOR) Per irRC |
NA; 17.5; NA; NA; NA; NA | — |
| SECONDARY Phase 1: Progression-free Survival (PFS) Per RECIST 1.1 |
1.8; 2.3; 1.6; 1.9; 7.9; 1.7 | — |
| SECONDARY Phase 1: Progression-free Survival (PFS) Per irRC |
1.9; 1.9; 1.6; 1.9; 3.4; 1.8 | — |
| SECONDARY Phase 2: Progression-free Survival (PFS) Per RECIST 1.1 |
3.9; 3.5; 2.2; 1.9; 4.4; 3.0 | — |
| SECONDARY Phase 2: Progression-free Survival (PFS) Per irRC |
4.2; 3.5; 5.4; 1.9; 5.8; 3.0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02460224). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.