Studie zur Bewertung der Wirksamkeit und Sicherheit neuer Kombinationstherapien mit LXH254 bei Melanom

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: 50-

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

Product Name: TRAMETINIB
Product Code: TMT212
Pharmaceutical Form: Film-coated 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: Capsule, hard
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: Film-coated 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 Code: LTT462
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: rineterkib
Current Sponsor code: LTT462
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: LTT462
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: rineterkib
Current Sponsor code: LTT462
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Code: LXH254
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: naporafenib
Current Sponsor code: L

Gender:
Female: yes
Male: yes

Inclusion criteria:
- Male or female must be = 18 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 checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents.
-Prior checkpoint inhibitor therapy in the unresectable or metastatic setting is not required for participants who have progressed on or within 6 months of adjuvant therapy with a checkpoint inhibitor.
-Prior therapy with T-VEC (talimogene laherparepvec) is allowed and will not be counted as a prior line of systematic therapy
-A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents administered with a CPI are permitted.
-To rule out pseudo-progression, participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. Confirmation is not required for patients who remained on treatment >6 months. Participants with BRAFV600 mutant disease:
-Participants must have received prior systemic therapy for unresectable or metastatic melanoma with a checkpoint inhibitor (CPI), either an anti-PD-1/anti-PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi (+/- CPI allowed) as the last prior therapy.
-Prior checkpoint inhibitor therapy in the unresectable or metastatic setting is not required for participants who have progressed on or within 6 months of adjuvant checkpoint inhibitors.
-Prior therapy with T-VEC (talimogene laherparepvec) is allowed and will not be counted as a prior line of systematic therapy
-A maximum of two prior lines of CPI-containing systemic immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents with CPI are permitted
-A maximum of one line of targeted therapy is allowed, and it must be the most recent line of therapy
-If a participant discontinued targeted therapy for reasons other than disease progression, a switch to another targeted therapy regimen is allowed
-Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy.
Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

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.
?= 2 weeks for small molecule therapeutics.
?= 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.
? = 4 weeks for chemotherapy agents, locally directed anti-neoplastic agents, or other investigational agents.
?= 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin c.
- 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