Phase 2
N=156
Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer
Colorectal Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01719380 ↗Enrolled (actual)
156
Serious AEs
60.3%
Results posted
Jun 2021
Primary outcome: Primary: Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1 — 0; 1; 1; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- LGX818 (Drug); Cetuximab (Drug); BYL719 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Oct 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1 |
0; 1; 1; 1; 0; 0 | — |
| PRIMARY Phase 2: Progression Free Survival (PFS) |
4.2; 4.9 | — |
| SECONDARY Number of Participants With Treatment - Emergent Adverse Events of Grade 3 or 4 Severity Based on National Cancer Institute of Common Terminology Criteria (NCI-CTCAE), Version 4.0 |
2; 4; 6; 7; 3; 5 | — |
| SECONDARY Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib) |
16.8; 11.7; 12.1; 12.3; 7.69; 14.2 | — |
| SECONDARY Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib) |
17.0; 24.4; 15.4; 22.4; 13.9; 31.1 | — |
| SECONDARY Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib) |
12.7; 12.1; 11.6; 11.7; 15.6 | — |
| SECONDARY Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib) |
16.5; 13.2; 13.7; 11.6; 18.3; 10.3 | — |
| SECONDARY Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib) |
104; 60.3; 62.8; 57.2; 49.2; 75.7 | — |
| SECONDARY Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib) |
78.4; 98.2; 78.6; 88.8; 66.8; 131 | — |
| SECONDARY Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib) |
112; 104; 105; 106; 123 | — |
| SECONDARY Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib) |
110; 97.0; 105; 82.5; 138; 75.4 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib) |
2.00; 1.99; 2.03; 2.17; 1.00; 2.02 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib) |
0.98; 1.98; 2.00; 3.92; 1.51; 2.00 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib) |
1.98; 3.97; 2.00; 2.10; 2.05 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib) |
1.97; 3.99; 2.15; 4.07; 2.02; 4.00 | — |
| SECONDARY Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib) |
23.98; 23.69; 24.03; 23.58; 23.00; 23.06 | — |
| SECONDARY Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib) |
23.78; 23.36; 23.92; 23.87; 23.89; 22.13 | — |
| SECONDARY Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib) |
23.00; 23.06; 22.76; 23.87; 23.17 | — |
| SECONDARY Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib) |
23.78; 23.36; 23.87; 23.87; 23.97; 23.08 | — |
| SECONDARY Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib) |
9.87; 20.5; 15.7; 20.6; 7.69; 10.4 | — |
| SECONDARY Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib) |
36.7; 108; 283; 66.0; 141 | — |
| SECONDARY Overall Survival (OS) |
15.0; 5.4; NA; 16.6; 6.6; 8.7 | — |
| SECONDARY Overall Response Rate (ORR) |
50.0; 14.3; 11.1; 25.0; 33.3; 25.0 | — |
| SECONDARY Duration of Response (DOR) |
10.6; 2.3; 21.7; 8.1; 3.9; 3.6 | — |
| SECONDARY Time to Response (TTR) |
2.8; 1.4; 3.9; 4.0; 1.5; 3.5 | — |
| SECONDARY Phase 1b: Progression Free Survival (PFS) |
12.0; 3.7; 2.8; 12.0; 5.4; 4.3 | — |
| SECONDARY Phase 2: Number of Participants With Any Variant in Gene Status at Baseline |
30; 34 | — |
Summary
This study will assess the safety and efficacy of LGX818 when combined with cetuximab or combined with cetuximab and BYL719 in patients with BRAF mutant metastatic colorectal cancer
Eligibility Criteria
Inclusion Criteria
- Metastatic colorectal cancer
- Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
- Life expectancy ≥ 3 months
- ECOG performance status ≤ 2
Exclusion Criteria
- Symptomatic or untreated leptomeningeal disease
- Symptomatic brain metastasis
- Patients with clinically manifested diabetes
- Acute or chronic pancreatitis
- Clinically significant cardiac disease
Other protocol-defined inclusion/exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT01719380). 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.