A Phase 2 interventional study of LGX818 and MEK162 in Metastatic Melanoma, sponsored by Fondazione Melanoma Onlus. Completed at 30 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-07.
Sponsored by Fondazione Melanoma Onlus · Phase 2, Interventional, and Treatment
To evaluate the best sequencing approach with the combination of target agents (LGX818 plus MEK162) and the combination of immunomodulatory antibodies (ipilimumab plus nivolumab) in patients with metastatic melanoma and BRAF V600 mutation.
The combination BRAF (B-raf murine sarcoma viral oncogene homolog B1) inhibitor plus mitogen-activated protein kinase (MEK) inhibitor seems to be more effective in the V600 BRAF mutated advanced melanoma patients compared to treatment with the BRAF inhibitors alone. In fact, a phase I-II study showed a better overall response rate (ORR) and progression-free survival (PFS) in the combination arm (dabrafenib plus trametinib) respect to the single agent treatment (dabrafenib): 76% and 9.4 months versus 54% and 5.8 months respectively. Another phase I study with a similar combination (vemurafenib plus cobimetinib) showed an ORR of 85% in vemurafenib-naïve patients.
Recently, the results of a phase I study about the combination ipilimumab plus nivolumab have been reported. In this study at the selected schedule (ipilimumab 3 mg/kg and nivolumab 1 mg/kg), 53% of patients had an objective response, all with tumor reduction of 80% or more. Reponses were durable, although longer follow-up is needed.
A recent phase I study has shown a high rate of liver toxicity with the combo ipilimumab plus vemurafenib . which makes difficult a combination with these two different drugs. Moreover, a better efficacy of the sequencing treatment BRAF inhibitors/ipilimumab vs. the single agent treatment was also observed; for this reason it was also suggested to start immunotherapy treatment in the BRAF V600 mutated melanoma population as first option, in order to increase the percentage of patients who can benefit from the sequencing, considering the possibility of a fast progression of the disease after the BRAF inhibitors treatment.
Taking into account these considerations, it seems impossible to think to combine all the four compounds (the target agents and immunomodulating monoclonal antibodies). The risk of a high rate of toxicity is realistic and would render this approach inapplicable.
Sequencing with these different combinations seems to be more feasible. However, also in this case it would be important to start with the best combination in order to give to the patients the best chance to increase the overall survival.
The aim of this prospective randomized phase II study is to evaluate the sequencing of these two different combinations and evaluate which is the best of these approaches.
3,073 studies on the registry are indexed under Melanoma; 529 are open to participants now.
This study's enrollment of 251 is above the median of 38 across 2,400 interventional studies indexed under Melanoma.
Browse Melanoma studies →Fondazione Melanoma Onlus is the lead sponsor of 7 studies on the registry; 1 is open to participants now.
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Adequate cardiac function:
Exclusion Criteria:
Combo Target (LGX818 450 mg p.o. od + MEK162 45 mg p.o. bid) until PD; then Combo Immuno (nivolumab 1 mg/kg solution IV combined with ipilimumab 3 mg/kg solution IV every 3 weeks for 4 doses then nivolumab 3 mg/kg solution IV every 2 weeks) until PD
Drug: LGX818 · Drug: MEK162 · Drug: Nivolumab · Drug: Ipilimumab
Combo Immuno (nivolumab 1 mg/kg solution IV combined with ipilimumab 3 mg/kg solution IV every 3 weeks for 4 doses then nivolumab 3 mg/kg solution IV every 2 weeks) until PD; then Combo Target (LGX818 450 mg p.o. od + MEK162 45 mg p.o. bid) until PD
Drug: LGX818 · Drug: MEK162 · Drug: Nivolumab · Drug: Ipilimumab
Combo Target (LGX818 450 mg p.o. od + MEK162 45 mg p.o. bid) for 8 weeks followed by Combo Immuno (nivolumab 1 mg/kg solution IV combined with ipilimumab 3 mg/kg solution IV every 3 weeks for 4 doses then nivolumab 3 mg/kg solution IV every 2 weeks) until PD; then Combo Target (LGX818 450 mg p.o. od + MEK162 45 mg p.o. bid) until PD
Drug: LGX818 · Drug: MEK162 · Drug: Nivolumab · Drug: Ipilimumab
LGX818 450 mg p.o. od
Also known as: Combo target, IMP3
MEK162 45 mg p.o. bid
Also known as: Combo target, IMP4
Nivolumab 1 mg/kg solution IV combined with ipilimumab 3 mg/kg solution IV every 3 weeks for 4 doses then nivolumab 3 mg/kg solution IV every 2 weeks
Also known as: Combo Immuno, IMP1
Nivolumab 1 mg/kg solution IV combined with ipilimumab 3 mg/kg solution IV every 3 weeks for 4 doses then nivolumab 3 mg/kg solution IV every 2 weeks
Also known as: Combo Immuno, IMP2
Overall Survival
OS is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive. OS data will be collected continuously while subjects are on study medication and every 3 months via in-person or phone contact after discontinuation of study medication
Time frame: Patients enrolled will receive study medication until disease progression, unaccettable toxicity, withdrawal of consent or death, whichever comes first, assested up to 24 month
Total Progression free survival
PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Tumor responses will be assessed by the Investigator according to RECIST Criteria (version 1.1)
Time frame: Baseline (Day 1), every 6 weeks until second disease progression is documented (Approximately around 2 years)
Percentage of patients alive at 2 and 3 years;
Percentage of patients alive at 2 and 3 years will be reported using Wilson score intervals.
Time frame: Time Frame: at 24^ and 36^ month
Best overall response rate (BORR);
It will be calculated as the percentage of ITT population patients who have a CR o o PR before any evidence of progression (as defined by RECIST).
Time frame: Time Frame: up to 24 months
Duration of response (DoR);
It will be calculated as the percentage of ITT population patients who have a CR o o PR before any evidence of progression (as defined by RECIST).
Time frame: Time Frame: up to 24 months
Toxicity of the investigational medicinal products (IMPs).
Safety and tolerability will be assessed in terms od AEs, laboratory data, ECG data, vitals signs and weight, which will be collected for all patients. AEs (both in terms od MedDRA preferred terms and CTCAE grade), laboratory data, ECG data, vital signs and weight will be listes individually by patient and summarized by treatment received. ECG changes will be summarized for each treatment group.
Time frame: Time Frame: up to 24 months
Quality of life and general health
Changes from baseline in EQ-5D and QLQ-C30 total score will be summarized by means of descriptive statistical methods.
Time frame: Time Frame: up to 24 months
3 years PFS rate
3 years PFS rate; calculated from the date of randomization;
Time frame: Time Frame: up to 36 months
Plan to share: No
This study is completed, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Encorafenib · Binimetinib · Nivolumab · Ipilimumab
Fondazione Melanoma Onlus