Therapy Detail
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| Therapy Name | LTT462 + LXH 254 |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| LTT462 | LTT 462|LTT-462|rineterkib | ERK Inhibitor (pan) 21 | LTT462 inhibits ERK, resulting in decreased downstream signaling, and reduced ERK-dependent proliferation and survival of tumor cells (NCI Drug Dictionary). | |
| LXH 254 | LXH254|LXH-254|Naporafenib | BRAF Inhibitor 25 CRAF Inhibitor 12 | LXH 254 is a RAF inhibitor that selectively inhibits monomeric and dimerized BRAF and CRAF, which may lead to anti-tumor activity in RAF-mutant tumors and better tolerability (AACR Annual Meeting 2019, Abstract LB-114, PMID: 31059256). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF G466A | lung non-small cell carcinoma | predicted - sensitive | LTT462 + LXH 254 | Case Reports/Case Series | Actionable | In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF G466A achieving SD with over 25% tumor reduction (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... |
| BRAF K601N | lung non-small cell carcinoma | predicted - sensitive | LTT462 + LXH 254 | Case Reports/Case Series | Actionable | In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF K601N achieving an unconfirmed PR (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... |
| NRAS mutant | melanoma | predicted - sensitive | LTT462 + LXH 254 | Phase II | Actionable | In a Phase II trial, combination treatment with LXH 254 and LTT462 demonstrated tolerable safety in patients with NRAS-mutant melanoma, and led to a disease control rate of 62% (18/29), with a confirmed partial response in 6 patients and stable disease in 12 patients (Ann Oncol (2022) 33 (suppl_7): S197-S224; NCT04417621). | detail... |
| BRAF V600E | lung non-small cell carcinoma | predicted - sensitive | LTT462 + LXH 254 | Case Reports/Case Series | Actionable | In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF V600E achieving an unconfirmed PR and 1 achieving SD with over 25% tumor reduction (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT02974725 | Phase I | LXH 254 + Ribociclib LXH 254 + Trametinib LTT462 + LXH 254 | A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma | Terminated | USA | SWE | POL | ITA | ISR | FRA | ESP | DEU | BEL | AUS | 1 |
| NCT04417621 | Phase II | LTT462 + LXH 254 Trametinib Ribociclib | Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma | Active, not recruiting | USA | NOR | NLD | ITA | ISR | GBR | FRA | DEU | CHE | BEL | AUS | ARG | 0 |
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