ArticleBMC medicine2023
First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03973151 (A Phase I/II, Single Arm, Dose Escalation and Cohort Expansion Study to Evaluate Safety, Preliminary Efficacy of HL-085 in Patients With NRAS Mutant Advanced Melanoma), which is not on this map. Cited by 11 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/II, Single Arm, Dose Escalation and Cohort Expansion Study to Evaluate Safety, Preliminary Efficacy of HL-085 in Patients With NRAS Mutant Advanced Melanoma
Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- The use of pharmacodynamic results for recommended phase II decision making in oncology clinical trials.Cancer chemotherapy and pharmacology · 2026Review
- Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Clinical characteristics and prognostic factors in patients with malignant melanoma: A Chinese prospective cohort study.World journal of clinical oncology · 2025Article
- Dissecting the MAPK signaling landscape in malignant melanoma: from BRAF and NRAS mutations to precision combination therapies.Frontiers in cell and developmental biology · 2025Review
- Article
- Tunlametinib (HL-085) plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors: an open-label, single-arm, multicenter, phase I study.Experimental hematology & oncology · 2024Article
- Multidisciplinary approach and treatment of acral and mucosal melanoma.Frontiers in oncology · 2024Review
- Review
- New Approaches to Targeted Therapy in Melanoma.Cancers · 2023Review
- Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor.Frontiers in pharmacology · 2023Article
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.
methodsThis was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D.
resultsBetween September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months.
conclusionsThe HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations.
trial registrationTrial registration ClinicalTrials.gov number: NCT03973151.
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