Study to Evaluate the Efficacy and Safety of New Combination Therapies with LXH254 for Melanoma

Argentina, Australia, Austria, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Norway, Poland, Switzerland, United Kingdom, United States (ICTRP)

Identifiant de l'essai ICTRP
EUCTR2020-000873-26 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
A randomized, open-label, multi-arm, two-part, phase II study to assess the efficacy and safety of multiple LXH254 combinations in patients with previously treated unresectable or metastatic BRAFV600 or NRAS mutant melanoma (BASEC)

Titre académique
A randomized, open-label, multi-arm, two-part, phase II study to assess the efficacy and safety of multiple LXH254 combinations in patients with previously treated unresectable or metastatic BRAFV600 or NRAS mutant melanoma (ICTRP)

Titre public
Study of efficacy and safety of LXH254 combinations in patients with previously treated unresectable or metastatic melanoma (ICTRP)

Maladie en cours d'investigation
previously treated unresectable or metastatic BRAFV600 or NRAS mutant melanoma
MedDRA version: 21.1Level: PTClassification code 10027480Term: Metastatic malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10027150Term: Melanoma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)

Intervention étudiée

Product Name: LXH254
Product Code: LXH254
Pharmaceutical Form: Tablet
INN or Proposed INN: LXH254
Current Sponsor code: LXH254
Other descriptive name: LXH254
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: TRAMETINIB
Product Code: TMT212
Pharmaceutical Form: Tablet
INN or Proposed INN: TRAMETINIB
Current Sponsor code: TMT212
Other descriptive name: TRAMETINIB DIMETHYL SULFOXIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Product Name: RIBOCICLIB
Product Code: LEE011
Pharmaceutical Form: Tablet
INN or Proposed INN: RIBOCICLIB
Current Sponsor code: LEE011
Other descriptive name: LEE011
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: RIBOCICLIB
Product Code: LEE011
Pharmaceutical Form: Tablet
INN or Proposed INN: RIBOCICLIB
Current Sponsor code: LEE011
Other descriptive name: LEE011
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Product Name: Not yet defined
Product Code: LTT462
Pharmaceutical Form: Capsule
INN or Proposed INN: LTT462
Current Sponsor code: LTT462
Other descriptive name: LTT462
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Not yet defined
Product Code: LTT462
Pharmaceutical Form: Capsule
INN or Proposed INN: LTT462
Current Sponsor code: LTT462
Other descriptive name: LTT462
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

(ICTRP)

Type d'essai
Interventional clinical trial of medicinal product (ICTRP)

Plan de l'étude
Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 6 (ICTRP)

Critères d'inclusion/exclusion
Gender:
Female: yes
Male: yes

Inclusion criteria:
- Male or female must be = 12 years
- For adolescents only (12-17 years): body weight > 40kg
- Histologically confirmed unresectable or metastatic cutaneous melanoma
- Previously treated for unresectable or metastatic melanoma:
- Participants with NRAS mutation:
- Participants must have received prior systemic therapy for unresectable or metastatic melanoma with an anti-PD-1/PD-L1 checkpoint inhibitor as a single agent or in combination with anti-CTLA-4. No additional systemic treatment is allowed for unresectable or metastatic melanoma
- A maximum of two prior lines of systemic immunotherapy for unresectable or metastatic melanoma are allowed
- The last dose of prior therapy (anti-PD-1, anti-PD-L1 or anti-CTLA-4) must have been received more than four weeks before randomization
- Participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. The last progression must have occurred within 12 weeks prior to randomization in the study
- Participants with BRAFV600 mutant disease:
- Participants must have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi as the last prior therapy. No additional systemic treatment is allowed for advanced or metastatic melanoma
- A maximum of three prior lines of systemic therapy for unresectable or metastatic melanoma are allowed
- The last dose of targeted therapy (last prior therapy) must have been received more than 2 weeks prior to randomization
- Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy. The last progression must have occurred within 12 weeks prior to randomization in the study
Other protocol-defined inclusion criteria may apply.

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55
(ICTRP)

Exclusion criteria:
Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
? = 4 weeks for radiation therapy or = 2 weeks for limited field radiation for palliation prior to the first dose of study treatment.
? = 4 weeks or = 5 half-life (whichever is shorter) for small molecule therapeutics.
? = 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.
- Participants participating in additional parallel investigational drug or medical device studies.
- All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are neurologically unstable
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
- Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
- Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
-Other protocol-defined inclusion/exclusion criteria may apply



Critères d'évaluation principaux et secondaires
Main Objective: To evaluate the anti-tumor efficacy of LXH254 in combination with novel agents including LTT462, trametinib, ribociclib in participants with previously treated unresectable or metastatic, BRAFV600 or NRAS mutant melanoma as measured by objective response rate.;Secondary Objective: - To characterize the safety and tolerability of each combination arm
- To further evaluate the efficacy of each combination arm;Primary end point(s): Confirmed objective response rate (ORR) using RECIST v1.1, per local assessment;Timepoint(s) of evaluation of this end point: Patient has at least 8 months or has progressed, died, discontinued study or started new anti-neoplastic therapy earlier. (ICTRP)

Timepoint(s) of evaluation of this end point: The first review for safety only will occur when the first 15 participants in each treatment combination arm (45 participants in each mutation group) have been enrolled and received 2 cycles of treatment or discontinued therapy. The second review will occur with the first interim analysis, when the first 30 patients have been enrolled and followed for 8 months or discontinued therapy. ;Secondary end point(s): To characterize the safety and tolerability of each combination arm
- incidence and severity of adverse events and serious adverse events
- dose interruptions, reductions, and permanent discontinuations

To further evaluate the efficacy of each combination arm
- Duration of response, progression-free survival, and disease control rate using RECIST 1.1
- Duration of response, progression-free survival, disease control rate, and objective response rate using RECIST 1.1 for all participants for the combination arms that moved to expansion

To evaluate the overall survival of each combination arm

To characterize the pharmacokinetics of each combination arm
- Serum/plasma concentration, pharmacokinetic parameters of each combination (ICTRP)

Date d'enregistrement
25.08.2020 (ICTRP)

Inclusion du premier participant
18.11.2020 (ICTRP)

Sponsors secondaires
non disponible

Contacts supplémentaires
Information&Communication M?dicales, icm.phfr@novartis.com, +33 1 5547 6600, Novartis Pharma S.A.S (ICTRP)

ID secondaires
CLXH254C12201, 2020-000873-26-NO (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000873-26 (ICTRP)