Entry Detail
| General information | |
| Database: | DB00191 |
| Objective: | Targeted BRAF inhibitors (BRAFi), alone or combined with MEK inhibitors (MEKi), lead to high overall response rates (ORRs) and increased survival in patients (pts) with BRAFmutant melanoma. Preclinical evidence of MAPK pathway reactivation in BRAFi and/or MEKi resistance support using additional rational combination therapies based on genetic alterations in tumors upon disease progression (PD). |
| Authors: | Dummer R., et al |
| Title: | LOGIC2:phase 2, multicenter, openlabel study of sequential encorafenib/binimetinib combination followed by a rational combination with targeted agents after progression, to overcome resistance in adult patients with locallyadvanced or metastatic BRAF V600 melanoma. |
| Journal: | European Journal of Cancer 2015 51 SUPPL. 3 (S667S668) |
| Year: | 2015 |
| PMID: | European Journal of Cancer 2015 51 SUPPL. 3 (S667S668) |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | BKM120 (PI3K inhibitor), BGJ398 (FGFR inhibitor), INC280 (cMet inhibitor) or ribociclib (LEE011 CDK4/6 inhibitor). |
| Target: | BKM120(PI3K delta, gamma, beta, alpha), BGJ398(Basic fibroblast growth factor receptor 1), LEE011(Cell division protein kinase 6 Cell division protein kinase 4) |
| Cancer Type: | melanoma |
| Cancer Subtype: | BRAF V600mutant melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 7 |
| Therapeutic Combination Content: | part 1: BRAFi encorafenib (LGX818; ENCO) + MEKi binimetinib (MEK162; BINI);part 2: ENCO/BINI + BKM120 (PI3K inhibitor), BGJ398 (FGFR inhibitor), INC280 (cMet inhibitor) or ribociclib (LEE011; CDK4/6 inhibitor). Pts with PD after ENCO/BINI treatment in a prior study may enter part 2 directly after genetic assessment with ENCO/BINI runin. |
| Study Type: | a phase II, multicenter, openlabel IIpart study |
| Key Patients Feature: | patients with locallyadvanced or metastatic BRAF V600 melanoma;All pts had prior antineoplastic therapy, including surgery (100%), medication (64%; >2 regimens, 19%), and radiotherapy (36%). |
| Biomarker: | BRAF V600 mutated; PI3K or CDKN2A/B alterations |
| Biomark Analysis: | NA |
| Control Group Info: | Part 1/runin: 36 pts (50% BRAFi/MEKi naive, 50% nonnaive; more than and equal to stage IV disease, 97%; ECOG PS 0/1/2, 67%/31%/3%)ยกรบ32 pts remain on part 1. Part 2: 4 pts with PI3K or CDKN2A/B alterations are enrolled ( BKM120, n = 2; ribociclib, n = 2). |
| Treatment Info: | In part 1/runin, pts naive to BRAFi/MEKi or pretreated with other BRAFi and/or MEKi receive BRAFi encorafenib (LGX818; ENCO) + MEKi binimetinib (MEK162; BINI) until PD(received oral ENCO 450 mg daily + BINI 45 mg twice daily.), then undergo tumor biopsy genetic assessment to determine combination treatment in part 2: ENCO/BINI + BKM120 (PI3K inhibitor), BGJ398 (FGFR inhibitor), INC280 (cMet inhibitor) or ribociclib (LEE011; CDK4/6 inhibitor). Pts with PD after ENCO/BINI treatment in a prior study may enter part 2 directly after genetic assessment with ENCO/BINI runin. |
| Primary End Point: | ORR by RECIST v1.1. |
| Secondary End Point: | safety, pharmacokinetics, and molecular status at baseline and PD. |
| Patients Number: | 36 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | ORR was 71% in 14 evaluable BRAFi/MEKi naive pts (1 partial response [PR], 9 unconfirmed PR [uPR]) and 42% in 12 evaluable nonnaive pts (2 PRs, 3 uPR). |
| Disease Control Rate: | Disease control rate was 86% (naive) and 50% (nonnaive). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common anycause adverse events (AEs) were mostly grade 1/2 and included diarrhea (25%), nausea (19%), fatigue (17%), and retinopathy (14%). Rash (11%), pyrexia (8%), and photosensitivity (0%) were infrequent. Serious AEs were conus medullaris syndrome, dyspnea, inguinal hernia, pulmonary alveolar hemorrhage, and urticaria (n = 1 each). |
| Conclusions: | As shown previously, ENCOBINI is active and well tolerated in BRAFiMEKinaive and nonnaive BRAFmutant melanoma. This ongoing study is further evaluating safety and efficacy in each part, particularly for pts receiving a genetically tailored triple combination upon PD. |