e21602 Background: Risk stratification of primary cutaneous melanoma based on Breslow thickness remains clinically imperfect, particularly in thin tumors (≤1 mm), where a subset progresses unexpectedly. Previously, targeted RT-PCR analyses of established tissue RNA markers demonstrated prognostic utility mainly in thick melanoma, with no robust markers identified for thin tumors, prompting an unbiased RNA sequencing approach to address this gap.Objectives: Identify RNA expression signatures associated with prognosis in thin (≤1 mm) and thick (≥4 mm) primary cutaneous melanoma. Methods: RNA-seq was performed on primary tumor tissue from 51 thin and 65 thick melanomas after hybrid-capture library preparation and deep sequencing (NovaSeq 6000, S4). Expression was quantified for 18,146 genes, including full coding regions of 17,702 protein-coding genes (54,142 transcripts), using a standardized four-step pipeline with stringent filtering. Analyses were performed by clinical outcome (regional recurrence and/or distant metastases and/or death) and to build classifiers distinguishing thin vs thick melanoma. Results: In thin melanoma, 69 genes were differentially expressed by outcome; a 10-marker panel (BAIAP2L1, DMRT3, ENSG00000305404, HOXA11-AS, MGP, MIR1183, MUC6, NBPF17P, NANOS3, TMEM191C) showed the best prognostic performance (AUROC 0.835). In thick melanoma, 26 prognostic genes were identified; a 6-marker panel (EEF1A1P16, HSPA8P5, IBSP, MEX3B, MMP3, VAMP2) achieved AUROC 0.93. A shared 4-marker signature (MMP3, RGS1, SPP1, VAMP2) performed consistently across thin and thick tumors (AUROC 0.80). A 5-marker classifier (ALOX12, COL22A1, KRT10-AS1, S100B, SPP1) distinguished thin vs thick melanomas (AUROC 0.96), supporting distinct transcriptional programs linked to thickness and progression biology. Conclusions: RNA profiling reveals substantial prognostic heterogeneity within thin melanoma and identifies multigene signatures that may refine risk stratification beyond Breslow thickness. Divergent prognostic panels in thin vs thick tumors suggest distinct mechanisms of progression and support development of clinically deployable RNA-based assays for risk-adapted management.These signatures identify biologically aggressive subsets within thin melanoma that may warrant intensified surveillance or consideration of adjuvant strategies.

e21519 Background: While anti-PD-1 is the first-line (1L) standard for BRAFwt advanced melanoma (aM), disease progression (PD) occurs in over half of patients, requiring second-line (2L) strategies. The ipilimumab/nivolumab (Ipi/nivo), though frequently used in 2L, is limited by toxicity and financial burden, and its ability to overcome resistance to prior immunotherapy is unclear. We aimed to assess different 2L options and the potential of Ipi/nivo based on prior anti-PD-1 response. Methods: A retrospective observational study approved by the IRB was conducted at two Russian centers: N.N. Blokhin NMRCO and Moscow Oncology City Hospital 62. We included all pts aged ≥18 yrs with BRAFwt aM who progressed on anti-PD-1 and were treated or consulted in these centers in 2023. We assessed the PFS from the start of 2L to PD, OS from the start of 1L (OS1) and 2L (OS2) to death from all pts and PFS, OS1 and OS2 in the Ipi/nivo group regardless of previous best response to anti-PD-1: complete and partial response (CR and PR), stable disease (SD), PD. Results: A total of 86 pts were included, 38 (44,2%) male and 48 (55,8%) female, with a mean age of 61,2 yrs. The 2L options are presented in the Table below. 4 patients were re-administered anti-PD-1 in the 2L after PD and local treatment for PD. mPFS was higher in the Pem/Len group but no statistically significant differences (SSD) were observed between all groups for either PFS, OS1 or OS2. Among pts in the Ipi/nivo group nearly half progressed on anti-PD-1 at the first CT/MRI assessment (see the Table). Only 6,2% had an objective response to anti-PD-1 earlier (CR+PR). Generally, the PD group had the lowest survival rates (the exception of the PR group of 2 pts), although no SSD were found between groups in PFS, OS1, and OS2. Conclusions: Ipi/nivo remains the primary 2L option for BRAFwt aM. No SSD between subgroups were found. The highest PFS in the Pem/Len may be attributed to the mechanism of action of this combination. Previous responses to anti-PD-1 in 1L may influence the effect of Ipi/nivo. These results need to be interpreted with caution given its retrospective nature and small number of pts in groups. Total n=86 (100%) Ipi/nivon=65 (75,6%) CTX10 (11,6%) Pem/Len5 (5,8%) Anti-PD-14 (4,7%) Trame (NRAS+)2 (2,3%) mPFS, mo 3,5 (3,0 - 6,2) 2,63 (2,3 - Na) 11,7 (3,6 - Na) 4,65 (3,5 - Na) 1,15 (1,0 - Na) mOS2, mo 21,8 (17,5 - 34,3) 8,8 (4,7 - Na) 11,5 (Na - Na) 13,7 (10,9 - Na) 1,3 (Na - Na) mOS1, mo 36,2 (28,1 - 55,4) 13,8 (12,3 - Na) Na 58,4 (21,8 - Na) Na (21,9 - Na) Survival in Ipi/nivo (n=65) Best response on anti-PD-1 in 1L CR2 (3,1%) PR2 (3,1%) SD20 (30,8%) PD32 (49,2%) Unk9 (13,8%) mPFS, mo 3,8 (3,8 - Na) 5,9 (5,8 - Na) 5,1 (2,8 - 10,2) 3,0 (2,6 - 6,2) 3,9 (2,8 - Na) mOS2, mo 34,3 (34,3 - Na) 6,7 (6,7 - Na) 32,1 (17,9 - Na) 18,2 (13,43 - 31,6) 39,1 (9,8 - Na) mOS1, mo 65,9 (65,9 - Na) 23,4 (23,4 - Na) 48,1 (30,8 - Na) 24,6 (20,9 - 36,9) 55,4 (31,8 - Na)

9548 Background: Metastatic uveal melanoma (mUM) remains a rare and aggressive malignancy. Immune checkpoint inhibitors (ICI) demonstrate modest activity, and real-world evidence comparing dual (nivolumab + ipilimumab) versus anti-PD-1 monotherapy, as well as the additive role of local therapy is limited. Methods: Multicenter retrospective observational study conducted in Russia (IRB-approved at participating centers). Outcomes assessed: median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 immune-related adverse events (irAEs). Stratified by treatment line, ICI type, and local therapy use. Univariable Cox proportional hazards regression was performed. Results: Patients with metastatic uveal melanoma treated between 2019 and 2025 were included (n=262). Of these, 25 patients (9.5%) who did not receive systemic treatment or received only palliative care were excluded. Among the full cohort: 158 (60.3%) were female, median age at primary diagnosis was 55.9 years, median time to metastatic disease was 2.42 years. Liver metastases were present in 90.8%. After exclusion, 237 patients were analyzed for survival. Results are presented in Table 1. Univariable Cox regression (after exclusion n=237): Dual ICI exposure (yes vs no): HR 0.60 (95% CI 0.44–0.84, p=0.003); Any ICI exposure (yes vs no): HR ≈0.72 (p=0.102) — non-significant trend. Conclusions: Dual ICI (nivolumab + ipilimumab) was associated with improved overall survival (HR 0.60, p=0.003), particularly with combination with local therapy (predominantly IHP, STRT, and TACE), which substantially enhanced ORR, DCR, PFS, and OS across ICI types. Patients who were unable to receive ICI in the first-line setting may be candidates for this option in the second-line; however, this requires further investigation through subgroup comparative analyses. Results. Treatment Line ICI Type Local Therapy n mPFS, mo (95% CI) mOS, mo (95% CI) ORR (%) DCR (%) Gr ≥3 irAEs (%) First-line Dual (nivo+ipi) Without 28 3.5 (3.0–6.6) 18.4 (13.4–33.5) 10.7 28.6 39.3 First-line Dual (nivo+ipi) IHP 60% STRT 35%TACE 5% 20 7.5 (6.2–18.2) 45.7 (23.4–NR) 45.0 80.0 45.0 First-line Mono anti-PD-1 Without 47 3.1 (2.8–3.7) 18.8 (11.9–27.5) 2.1 14.9 2.1 First-line Mono anti-PD-1 STRT 50%IHP 40%TACE 6.7%RFA 3.3% 30 7.53 (4.5–12.3) 27.9 (18.6–NR) 36.7 60.0 16.7 Second-line Dual Without 35 3.3 (2.5–5.5) 13.1 (9.3–18.8) 2.9 31.4 45.7 Second-line Dual STRT 100% 3 9.3 (8.7–NR) 39.1 (9.6–NR) 33.3 100.0 33.3 Second-line Mono anti-PD-1 Without 15 9.0 (5.2–21.6) 21.3 (14.8–NR) 13.3 46.7 0 Second-line Mono anti-PD-1 STRT 50%IHP 25%TACE 25% 8 8.6 (4.7–NR) 17.3 (13.3–NR) 0 75.0 0

9541 Background: The development of clinically comparable biosimilars of key immuno-oncology agents is essential to improving global access to effective therapy. BCD-201 is a proposed pembrolizumab biosimilar that has shown high analytical similarity in preclinical studies, and pharmacokinetic equivalence to the reference pembrolizumab in phase I study (NCT05739006).This phase III trial evaluated the clinical equivalence of BCD-201 versus reference pembrolizumab in patients with advanced melanoma. Methods: This international, multicenter, randomized, double-blind phase III study enrolled adult patients with unresectable or metastatic cutaneous melanoma. Patients were randomized 1:1 to receive BCD-201 or reference pembrolizumab 200 mg IV every 3 weeks for 24 weeks. Randomization was stratified by ECOG (0 vs 1), PD-L1 expression (<5% vs ≥5%), and disease stage (AJCC 7th edition M0/M1a/M1b vs M1c). The primary endpoint was objective response rate (ORR) per RECIST v1.1 assessed by blinded independent central review (BICR) at week 24 in the ITT population. Equivalence was concluded if the 95% confidence interval (CI) for the ORR difference fell within prespecified margins of −15% to +15%. Secondary efficacy endpoints included ORR per iRECIST, progression-free survival (PFS), overall survival (OS). Results: A total of 479 patients were included in the ITT population (BCD-201, n=234; reference pembrolizumab, n=245), with balanced baseline characteristics. At week 24, ORR was 33.3% in the BCD-201 group and 32.7% in the reference pembrolizumab group in ITT population. The unstratified ORR difference was 0.7% (95% CI −7.7 to 9.1), fully within the prespecified equivalence margins. Results were consistent across per-protocol and stratified sensitivity analyses. Secondary efficacy endpoints, including ORR per iRECIST, OS, and DOR, were comparable between groups. At 24 weeks, PFS rates were 51.9% for BCD-201 and 50.5% for reference pembrolizumab per RECIST 1.1. OS rate at 24 week was 90.2% in the BCD-201 group and 89.3% in the reference pembrolizumab group. Longer-term efficacy and safety data will be reported in future analyses. Safety profiles were similar between groups, with grade ≥3 AEs reported in 19.7% and 21.9% of patients for BCD-201 and reference pembrolizumab. Main PK parameters (AUC and C max ) met equivalence criteria. Immunogenicity was low and comparable between groups, with binding antibodies (Abs) detected in 7 (3.1%) and 6 (2.6%) patients in the BCD-201 and comparator groups, respectively. No neutralizing Abs were detected. Conclusions: BCD-201 demonstrated equivalent efficacy to reference pembrolizumab with comparable safety, pharmacokinetics, and immunogenicity in patients with advanced melanoma. These data support BCD-201 as a pembrolizumab biosimilar and highlight its potential to expand access to anti-PD-1 therapy. Clinical trial information: NCT05986331 .

e24191 Background: Immune checkpoint inhibitors (ICI) significantly improve survival in cancer patients but are frequently associated with dermatologic immune-related adverse events (irDAEs) that exhibit clinical heterogeneity and may mimic psoriasis. The histopathological distinctions between ICI-induced psoriasis vulgaris and psoriasiform irDAEs remain insufficiently characterized despite their critical importance for accurate diagnosis and treatment decisions. Study Design: Multicenter prospective study including patients who developed irDAEs during ICI therapy and underwent clinical evaluation with or without skin biopsy. Retrospective data collection included demographics, oncologic characteristics, ICI regimens, cutaneous manifestations, CTCAE severity grading, and available histopathological findings, with histologic analysis focused on psoriasiform cases. Methods: The study included 50 patients who developed immune-related cutaneous adverse events during ICI therapy (mean age 69 years; 56% male). The most common underlying malignancies were skin and soft tissue cancers (38%), genitourinary cancers (28%), and lung/bronchial cancers (20%). Results: Isolated pruritus without visible rash was observed in 20 patients (40%). The remaining 30 patients (60%) developed irDAEs of varying severity: Grade 1 in 19 patients (38%), most commonly maculopapular rash (26%), and Grade 2–3 in 11 patients (22%), including psoriasis vulgaris (8%), psoriasiform eruptions (6%), lichenoid eruptions (6%), and bullous pemphigoid (2%). Histopathological evaluation was performed in 7 patients with Grade 2–3 psoriasis vulgaris (n = 4) or psoriasiform eruptions (n = 3). Psoriasiform eruptions showed irregular acanthosis with prominent parakeratosis, preserved granular layer, and mild dermal vascular changes with moderate perivascular lymphocytic infiltrates, whereas psoriasis vulgaris demonstrated regular acanthosis, diffuse parakeratosis, complete loss of the granular layer, and pronounced papillary dermal vascular dilatation with prominent perivascular inflammation. Conclusions: Routine histopathological assessment of the skin is essential for the accurate confirmation of irDAEs. Morphological findings enable the differentiation of these events from other dermatoses and provide a rationale for selecting supportive treatment without unjustified modification of antitumor therapy.

e21527 Background: The optimal immunotherapy strategy for patients with BRAF-mutant advanced melanoma who progress on first-line BRAF/MEK inhibitors remains undefined. While anti–PD-1 monotherapy is commonly used, combination ipilimumab/nivolumab (Ipi/Nivo) offers potentially superior efficacy but with a higher toxicity burden. This study directly compares these two standard approaches in this patient population in routine practice. Methods: A retrospective, multicenter observational analysis of adult patients with BRAF V600–mutant advanced melanoma who progressed on BRAF/MEK inhibitors and were managed at two Russian centers (N.N. Blokhin NMRCO and Moscow Oncology City Hospital No. 62) from 2019 to 2023. This retrospective analysis included 63 patients with advanced melanoma who received first-line (1L) combined targeted therapy (e.g., BRAF/MEK inhibitors) and, upon progression, initiated second-line (2L) immunotherapy. Patients received either ipilimumab plus nivolumab (Ipi/Nivo) (n = 46) or anti–PD-1 monotherapy (n = 17). Results: Treatment assignment information was available for all 63 patients (Ipi/Nivo combination, n = 46; anti-PD-1 monotherapy, n = 17). The median age of all included patients was 50.4 years; 54.3% were male. Metastatic stage at treatment initiation differed between groups (M1d: 50.0% vs 35.3%; M1c: 28.3% vs 35.3%), respectively. The median duration of follow-up after second-line treatment initiation was 26.9 months. The objective response rate (ORR; complete and partial responses) to second-line immunotherapy was 19.0%. Combination immunotherapy did not increase ORR compared with monotherapy (19.6% with ipilimumab/nivolumab vs 17.0% with anti–PD-1 therapy). The majority of patients (85.7%) had documented disease progression on 2L therapy, confirming an aggressive, treatment-resistant population The median progression-free survival (mPFS) was 5.5 months (95% CI, 3.00–13.6) in the ipilimumab/nivolumab group and 4.7 months (95% CI, 3.33–23.8) in the anti–PD-1 therapy group. The median overall survival (OS) was 28.7 months (95% CI, 12.03–45.4) in the ipilimumab/nivolumab group and 35.8 months (95% CI, 25.1–46.5) in the anti–PD-1 therapy group, with a hazard ratio (HR) of 0.98 (95% CI, 0.49–1.95; p = 0.956). Conclusions: Second-line immunotherapy provided modest disease control with a high primary progression rate. No significant efficacy difference was observed between anti–PD-1 monotherapy and ipilimumab/nivolumab combination as a 2L strategy, suggesting limited benefit from intensification to combination immunotherapy after targeted therapy failure in this setting. These results need to be interpreted with caution given the retrospective nature of the analysis and the small number of patients in the treatment groups.

9544 Background: BCD-217-2/OCTAVA is an international, multi-center, randomized, double-blind, placebo-controlled phase III study conducted to assess the efficacy and safety of nurulimab +prolgolimab (nuru + prolgo ) combination therapy with continued prolgolimab therapy compared to prolgolimab monotherapy at the 1st line treatment of patients (pts) with unresectable or metastatic melanoma (un/mM). BCD-217 is a fixed-dose combination of nurulimab (aCTLA-4, 5 mg/ml) and prolgolimab (aPD-1, 15 mg/ml) which was recently approved for this indication in Russia and Belarus. Here we present efficacy results based on 24 mos of therapy. Methods: Treatment-naïve pts with un/mM (stage IIIC–IV) were randomized 1:1 to two arms. The nuru+prolgo arm received a combo of nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) at 0.2 ml/kg Q3W for the first four infusions. The prolgo arm received prolgolimab monotherapy (3 mg/kg Q3W) for the first four infusions. Both arms then received prolgolimab maintenance therapy for up to two years. The primary endpoint of the study was PFS. Results: 271 pts were randomized to nuru+prolgo (n=135) or prolgo monotherapy (n=136) arms. After a median follow-up of 24.7 mos the mPFS was 15.4 (95% CI 8.4; NA) mos in the nuru+prolgo arm and 8.3 (95% CI 4.2; 14.8) mos in the prolgo monotherapy arm (HR 0.696, 95% CI 0.502; 0.965), iRECIST, ITT population). The PFS benefit was consistent per RECIST 1.1 (HR 0.717, 95% CI 0.533; 0.964). ORR, DCR and TTR were also higher in nuru+prolgo arm. mOS was not reached in both groups (HR 0.836, 95% CI 0.495; 1.41). 24-mos OS was 76.1% in nuru+prolgo arm and 71.7% in prolgo arm respectively. The mDOR was also not reached in any arm, meaning that more than half of the pts who responded to therapy maintained their response until the end of the FU period. Grade ≥3 treatment-related AEs occurred in 17.8% of pts (nuru+prolgo) vs 13.2% (prolgo). Gr ≥3 irAEs were 14.1% vs 5.1%, respectively (p=0.0126). Any-grade irAEs were reported in 51.9% vs 33.8% of cases (p=0.0027). Treatment discontinuation due to AEs was 11.1% vs 5.1%. Conclusions: The OCTAVA trial results demonstrated a statistically significant and clinically meaningful improvement in PFS for the 1st line low-dose nuru + prolgo combination followed by prolgo maintenance, compared to prolgo monotherapy, in patients with unresectable or metastatic melanoma. This efficacy benefit was accompanied by manageable rate of immune-related AE, consistent with the known profile of CTLA-4/PD-1 combinations. These results support the use of the nuru + prolgo regimen as a valuable 1st line treatment option for this population. Clinical trial information: NCT05732805 .

e21520 Background: Post–anti–PD-1 advanced melanoma has few effective salvage options and CHEMO outcomes are modest. We evaluated real-world comparative effectiveness (incl. OS) of LENVA+Pembro versus non-Lenva-based therapy after anti–PD-1 progression, given encouraging activity in LEAP-004 despite negative 1L data in LEAP-003. Methods: Single-center retrospective RWD study at N.N. Blokhin NMRCO using the full EMR (01/2022–09/2025; 37,942 records; 7,061 pts). Advanced cutaneous melanoma pts progressing after anti–PD-1 were identified (ICD-10 C43 + free-text; non-cutaneous primaries manually excluded). Results: Treatment assignment was available for 235 patients (chemo without lenva, n = 117; lenva-based regimen, n = 118). Baseline characteristics were broadly similar: median age 59 (32–95) vs 61 (25–86) years, men 46.2% vs 37.3%, BRAF-mutant 30.8% vs 28.0%, and metastatic stage at treatment start (M1d 26.5% vs 22.9%; M1c 32.5% vs 32.2%). Prior ipilimumab was more frequent in the lenva group (66.1% vs 56.4%). The main imbalance was the therapy line: among patients with documented lines (70/117 and 80/118), the median line was 2 (1–6) vs 2.5 (1–6) and ≥3rd line used 42.9% vs 50.0%. Median FU was 16.2 mo (95% CI 11.2–22.2) with chemo and 14.4 mo (95% CI 10.8–22.6) with lenva. In OS Kaplan–Meier analysis (N = 235; 82 deaths), median OS was 77.2 mo (95% CI 24.5–NR) with chemo (37 deaths) and 24.6 mo (95% CI 13.4–NR) with lenva-based therapy (45 deaths) (log-rank p = 0.183). A multivariable Cox model with time-varying lenva effect was fitted in pts with known BRAF (WT/mutant) and complete covariates (n = 129; 46 deaths), adjusting for age, BRAF, metastatic stage at treatment start, prior ipilimumab, and line of therapy. Line of therapy was independently associated with OS (HR 1.36 per one-line increase; 95% CI 1.03–1.79). To account for non-proportional effects, lenva exposure was modeled piecewise (0–6, 6–12, ≥12 months), yielding interval-specific hazard ratios vs chemotherapy-only: 0–6 mo HR 0.82 (95% CI 0.35–1.92), 6–12 mo HR 3.13 (0.65–14.99), and ≥12 mo HR 3.11 (0.80–12.09). The proportional hazards test for the interval-specific lenva effect was borderline (p = 0.063), while the global test was not significant (p = 0.27). Exploratory effect-modification analyses did not identify heterogeneity of the time-varying lenva association by therapy line across pre-specified cutoffs (likelihood ratio tests for interaction p = 0.20 for 1 vs ≥2, p = 0.81 for 1–2 vs ≥3, and p = 0.13 for 1–3 vs ≥4), noting limited power and sparse events in early-line strata. Conclusions: LENVA-based salvage was not associated with improved OS vs CHEMO in aPD-1–refractory melanoma and effect estimates were time-dependent/uncertain amid strong confounding by therapy line. These data do not justify prioritizing a LENVA-vs-CHEMO prospective trial and highlight the need for new strategies in PD-1–resistant disease.

e21576 Background: Cutaneous melanoma is the most aggressive form of skin cancer, necessitating reliable prognostic markers for risk stratification. Despite the availability of clinical parameters such as Breslow thickness and ulceration, accurate molecular prognostic markers remain a major unmet need. Molecular tools like DecisionDx-Melanoma (31 genes) and MelaGenix (11 genes) provide advanced risk classification for recurrence and survival. Previously, we identified novel RNA markers distinguishing melanomas from nevi (NCT04353050), distinct from those commonly investigated for prognostication. These markers include melanoma-specific CXCL8, DUXAP8/9/10, MAGEA3/6/12, and nevus-specific circCDR1-AS (LINC00632) and CMIP. This study evaluates whether these markers serve as reliable prognostic indicators in melanoma patients. Methods: Formalin-fixed, paraffin-embedded (FFPE) melanoma samples from 120 patients (59 with good prognosis, 61 with poor prognosis) were analyzed. Good prognosis was defined as event-free survival of ≥10 years, while poor prognosis was defined as recurrence, metastasis, or death within ≤5 years. A previously validated RT-PCR panel was employed to assess correlations between marker expression and prognosis. Results: Of 120 melanoma samples, informative results were obtained for 119 using standard procedures. Among the 120 samples, 80 showed definitive melanoma-specific markers, 27 fell into a "grey zone," and 13 exhibited no conclusive melanoma markers. Expression levels of melanoma-specific markers correlated with Breslow thickness but not prognosis. We performed a subgroup analysis stratified into thick (≥4 mm) and thin (≤1 mm) melanomas (Table). The strong prognostic value of CXCL8 and DUXAP8_9_10 in thick melanomas suggests their involvement in aggressive tumor behavior, potentially linked to inflammatory and proliferative pathways. CMIP expression inversely correlated with poor prognosis, indicating its possible role in less aggressive melanoma subtypes. In contrast, no markers demonstrated significant prognostic utility in thin melanomas, highlighting the need for alternative molecular signatures. Conclusions: These findings suggest that RNA marker panels could enhance current prognostic models for thick melanomas. However, their utility in thin melanomas remains limited, warranting further investigation into alternative molecular signatures. Future studies should focus on identifying additional biomarkers to improve risk stratification in early-stage melanoma patients. Marker AUROC P value RNA-markers prognostic significance in thick (≥4 mm) melanomas CXCL8 0.65 0.004 CMIP 0.37 0.011 DUXAP8_9_10 0.61 0.032 cirCDR1.AS 0.41 0.083 MAGEA3_6 0.54 0.470 RNA-markers prognostic significance in thin (≤1 mm) melanomas DUXAP8_9_10 0.32 0.021 MAGEA3_6 0.35 0.056 cirCDR1.AS 0.59 0.285 CXCL8 0.59 0.318 CMIP 0.48 0.838

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

BCD-217-2/OCTAVA (NCT05732805) is an international, multi-center, randomized, double-blind, placebo-controlled phase III study conducted to access the efficacy and safety of prolgolimab+nurulimab (BCD-217) combination therapy with continued prolgolimab therapy compared to prolgolimab monotherapy as 1st line treatment for patients (pts) with unresectable or metastatic melanoma (un/mM). BCD-217 is a fixed-dose combination of nurulimab (aCTLA-4, 5 mg/ml) and prolgolimab (aPD-1, 15 mg/ml) was recently approved as the 1st line treatment for un/mM in Russia. Here we present the primary analysis of the study. Pts with unresectable or metastatic cutaneous melanoma (IIIC-IVM1a-c) with treatment- naïve for unresectable/metastatic disease were randomized in 2 treatment arms: combination drug containing nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) at a dose of 0.2 ml/kg Q3W during the first four blinded infusions (nuru+prolgo arm) and prolgo arm received prolgolimab monotherapy at a dose of 3 mg/kg Q3W during the first four blinded infusions. Then both arms received prolgolimab maintenance up to two years. The primary endpoint of the study was progression-free survival (PFS). 271 pts were randomized to nuru+prolgo (n=135) or prolgo monotherapy (n=136) arms. After the median of 15.8 mo follow-up the median PFS (mPFS) was 15.4 (10.3; ND) mo in the nuru+prolgo group and 10.8 (4.7; ND) mo in the prolgo monotherapy group (95% CI, HR 0.68 (0.482; 0.957), iRECIST). The mPFS benefit of nuru+prolgo arm compared to prolgo arm are maintained in RECIST 1.1 assessment: 9.9 mo vs 2.8 mo, respectively. ORR and DCR were also higher in NURU+PROLGO arm. mOS was not reached in both groups (95% CI, HR 0,88, (0.50; 1.55)). 12-mos OS was 84% in each arm. Grade 3-4 treatment-related AE were reported in 16.3% of pts in nuru+prolgo arm compared to 14.0% - prolgo arm. Immune-related AEs (irAE) of all grades were reported in 52.6% of cases in nuru+prolgo arm and 32.4% of cases - in prolgo arm (p 0.0007). Majority of them were mild. The proportion of gr.≥3 irAEs was 13.3% vs 5.9% in nuru+prolgo arm and prolgo arm, respectively (p 0.04). Treatment discontinuation due to AE was reported in 9.6% of cases for nuru+prolgo vs 4.4% of cases for prolgo arm. OCTAVA trial resuts demonstrated that the fixed-dose combination of nurulimab + prolgolimab is significantly more effective than aPD-1 monotherapy without a serious deterioration of the safety profile in patients with metastatic or unresectable cutaneous melanoma as 1st line therapy. Lev Demidov, Igor Samoylenko, Galina Kharkevich, Kristina Orlova, Vladimir Moiseenko, Igor Utyashev, Daniil Stroyakovskiy, Vadim Kozlov, Anastasia Mochalova, Svetlana Demidova, Marina Lyadova, Andrey Kutkovich, Pavel Skopin, Nadezhda Kovalenko, Sufia Safina, Vitaliy Volkov, Yulia Semiletova, Vera Vaschenko, Nikolaiy Kislov, Artem Poltoratsky, Irina Shumskaya, Sergey Kolomiets, Alexander Sobolev, Igor Belogortsev, Svetlana Odintsova, Sameer Rastogi, Timur Andabekov, Anastasia Zimina, Konstantin Penkov, Anna Semenova, Alexey Obukhov, Vasiliy Belyakovsky, Oleg Gladkov, Rakesh Neve, Natalia Falaleeva, Elena Poddubskaya, Amale Vaibhav, Dmitriy Kirtbaya, Yana Chapko, Maria Smagina, Irina Sorokina, Yulia Linkova, Arina Zinkina-Orikhan, Fedor Kriukov, Anton Lutsky, Evgenia Mikhailova. Proved clinical benefit of low-dose anti-CTLA4 + anti-PD-1 immunotherapy versus mono anti-PD-1 therapy in patients unresectable or metastatic melanoma: Phase III OCTAVA trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 653.

Adjuvant therapy for BRAF-mutated stage III melanoma patients includes targeted therapy (dabrafenib + trametinib) and anti-PD-1 immunotherapy (pembrolizumab or nivolumab). Direct comparative studies are lacking, and data are limited to retrospective analyses. The aim of our study was to compare the efficacy of these regimens in a Russian patient population in real-world clinical practice among patients with BRAF mutations. Material and methods. A single-center retrospective study was conducted. We included patients with stage III melanoma with a BRAF mutation who received adjuvant therapy between January 2019 and December 2022. All included patients were treated or consulted at the N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health. The primary endpoint was relapse-free survival (RFS), and secondary endpoints included overall survival (OS), progression-free survival (PFS) for patients who experienced progression, the rate of distant metastasis and toxicity. Results. The study included 246 patients: 107 received targeted therapy (TT), 122 received immunotherapy (IT), and 17 were under observation (this group was not analyzed). The median follow-up was 38.5 months. The median RFS was 44 months in the TT group and 39 months in the IT group (HR 0.79, 95% CI 0.55–1.15, p = 0.22). The one- and two-year RFS rates were 88.8% (95% CI 83–95) and 63.1% (95% CI 54.5–73) in the TT group and 61.5% (95% CI 53.4–70.7) and 54.1% (95% CI 45.9–63.7) in the IT group respectively. The median OS was not reached in either group (HR 0.59, 95% CI 0.28–1.25, p = 0.169). The one- and two-year OS rates were 100% (95% CI 100–100) and 95.2% (95% CI 91.2–99.4) in the TT group and 94.3% (95% CI 90.2–98.5) and 88.5% (95% CI 83–94.3) in the IT group respectively. No new or unexpected toxicity was reported in either treatment group. Progression occurred in 117 patients: 51 in the TT group (10 during adjuvant therapy and 41 after its completion) and 66 in the IT group (41 during adjuvant therapy and 25 after its completion). The rate of distant metastasis was higher in the TT group (68.6 vs 53%, p = 0.08). After progression, patients more frequently received alternative therapies. The median PFS was 9 months in the TT group and 15 months in the IT group (HR 1.23, 95% CI 0.74–2.05, p = 0.414). Conclusions. Targeted therapy demonstrated a numerical advantage in RFS and OS compared to immunotherapy, although these differences were not statistically significant. Targeted therapy may be more effective in preventing early relapses. The absence of statistically significant differences needs longer follow-up to assess long-term outcomes. The retrospective nature of the study and the lack of randomization limit the reliability of the conclusions.

Background. Locally advanced (laBCC) and metastatic basal cell carcinoma of the skin (mBCC) have a poor prognosis. Hedgehog (Hh) pathway inhibitors, such as vismodegib and sonidegib, are highly effective in treatment of advanced forms of BCC. Aim. To evaluate the efficacy and safety of sonidegib in the investigator-initiated observational study B-SURE (Basal cell carcinoma – Sonidegib Use in Real-world Evidence) in patients with laBCC and mBCC in real-world clinical practice in the Russian Federation as first-line therapy (in patients with no history of treatment with Hh inhibitors), as well as in patients with a history of treatment with vismodegib (another Hh pathway inhibitor). Materials and methods. The study included 10 patients, 9 with laBCC and 1 with mBCC. Patients visited clinical center in accordance with routine clinical practice and underwent standard procedures and examinations in accordance with clinical guidelines and the physician’s decision. Visit intervals were 3–4 months. Data on patients’ use of sonidegib was collected during visits to the clinical site, and the efficacy of sonidegib therapy was assessed according to RECIST 1.1 criteria. The patients also completed the EORTC QLQ-C30, version 3, and the EQ-5D-5L, version 1.2, before starting sonidegib therapy and every 3 months thereafter during routine visits to clinic. Results. At the time of data analysis (September 2025), the efficacy of sonidegib therapy was evaluated in 9 patients, while tolerability and safety were evaluated in all 10 patients. Three patients had a history of vismodegib therapy, which was discontinued due to disease progression (n=1), intolerance (n=1), and intolerance with a complete clinical response (n=1). The median time from diagnosis to the development of laBCC and mBCC was 67.5 months. In patients with no prior vismodegib treatment, objective responses were observed in 4 of 7 patients (2 complete, 2 partial responses), yielding an objective response rate (ORR) of 57%. In patients with a history of vismodegib treatment, an objective response was reported in 1 of 3 (complete response in 1), yielding an ORR of 33.3%. The safety profile of sonidegib included adverse events (AEs) in 7 (70%) of 10 patients, mainly of Grade 1-2, which did not require a change in the dose regimen. Severe AEs (Grade 3-4) leading to discontinuation were reported in 1 patient (10%). It is noteworthy that in three patients with severe AEs during previous vismodegib therapy, sonidegib treatment was not associated with such complications, suggesting different safety profiles of these agents. Conclusion. For the first time, the efficacy of sonidegib, with an ORR of 57%, was demonstrated in a Russian population of Hh inhibitor-naive patients with laBCC and mBCC. Sonidegib demonstrated an acceptable safety profile, with a low discontinuation rate (10%) due to AEs. Particular attention should be given to the favorable tolerability of sonidegib in patients with a history of severe toxicity during vismodegib therapy, which expands the therapeutic options in case of intolerance to another Hh-inhibitor.

Purpose : To conduct a comparative analysis of the diagnostic effectiveness of elastography and elastometry in detecting melanoma metastases in lymph nodes using histological examination of a macropreparation as a reference method. The data obtained can help in the development of algorithms for noninvasive diagnostics and reduce the number of unjustified surgical interventions. Materials and methods : A prospective study of 14 macro-preparations of metastatically affected lymph nodes removed from patients with skin melanoma during elective surgical interventions was conducted. Conclusion : An integrated ultrasound approach combining elastography and elastometry demonstrates high accuracy in detecting metastatic lymph node lesions in skin melanoma.

Introduction. Skin melanoma, despite having similar clinical and histological characteristics, can have different prognoses. Gene expression profiling potentially allows for more accurate risk stratification of patients. Aim. To study prognostic test systems for assessing outcomes in patients with skin melanoma based on the analysis of primary tumors. Materials and methods . A systematic literature review (scoping review) was conducted in accordance with PRISMA-ScR principles. The search was performed in PubMed (2008–2024). Two independent reviewers conducted the study selection and data analysis to assess concordance. The data were presented descriptively. Results . Out of 149 identified publications, 31 studies were included in the review. The effectiveness of four test systems was evaluated, with the most frequently used being DecisionDx-Melanoma (19/31, 61.3%). This test stratifies patients by molecular classes: patients at high risk were found to have a 5.33 (±1.25) times higher likelihood of disease progression and poorer survival rates compared to lower-risk patients. No studies included data on the Russian population. Conclusions . Gene expression profiling demonstrates high accuracy in predicting outcomes for patients with skin melanoma.

Background. Basal cell skin carcinoma (BCSC) is the most common skin cancer. Most cases are diagnosed early and successfully treated using local methods. However, a small proportion of patients develop locally advanced or metastatic BCRCs, which is a challenging clinical issue. The number of locally advanced and/or metastatic forms of BCSCs is based on the experience of individual centers or the analysis of individual databases because the skin cancer cases generally are coded and accounted under the C44 category without counting separately the nosological forms and data on the disease prevalence. Aim. To estimate the number of patients with locally advanced and metastatic BCRCs among all patients treated in the N.N. Blokhin National Medical Research Center of Oncology from 2019 to July 2024 with the diagnosis code C44 according to the International Classification of Diseases, 10th Edition. Results. Between 2019 and July 2024, 3,801 individual cases of non-melanoma skin cancer (C44) were reported. Most of the 3,801 patients had BCSCs (n=2,796, 73.6%), followed by squamous cell carcinoma (n=857, 22.5%), Merkel cell carcinoma (n=100, 2.6%), and other skin tumors and neoplasms originating from the skin appendages (n=48, 1.3%). Among all cases of BCSCs, 94 (3.4%) cases of locally advanced and metastatic forms of the disease were reported. These patients were divided into two groups: with locally advanced BCSC (78 patients, 2.8%) and metastatic BCSC (16 patients, 0.6%). Conclusion. Most patients with early stages of BCSCs can be completely cured with radical surgery and/or radiation therapy, and a small number of patients develop disease progression that is not amenable to surgery or radiation therapy. We obtained the following results: 2.8% of locally advanced BCSCs and 0.6% of metastatic BCSCs, which is consistent with the literature data, where locally advanced BCSCs are reported in 1-2% of patients, and BCSC metastasis is reported in 0.0028-0.55%.

Background. Adjuvant targeted therapy (ATT) with a combination of dabrafenib and trametinib after radical surgical treatment in patients with stage III skin melanoma (SM) with a BRAF V600 mutation reduces the risk of disease recurrence. The effectiveness of this approach has been demonstrated in randomized clinical trials, and also confirmed in several large non-Russian real-world (RW) studies. Aim. To evaluate, in RW settings, the effectiveness of ATT with a combination of dabrafenib and trametinib after definitive surgical treatment in patients with BRAF V600-positive SM in Russia. Materials and methods. The RATIONALE study is a prospective, non-interventional, multicenter RW study. The follow-up duration for the study was 1 year. Patients with SM older than 18 years who had previously started dabrafenib and trametinib therapy no more than 8 weeks prior to Visit 1 were included in the study. The paper presents results from the analysis of Cohort 1 only (patients who received dabrafenib and trametinib in the adjuvant setting). Results. The cohort included 214 patients with BRAF V600-mutated SM of stages IIIA–D and IV resectable. At the time of therapy initiation, the majority of patients were stage IIIc (54.7%) or IIIb (22.0%). The most common mutation – BRAF V600E – occurred in 66.3% of cases, while the second most common variant – BRAF V600 not otherwise specified – was detected in 31.3%. One-year overall survival for all included patients was 94%, one-year relapse-free survival was 84%, and one-year distant metastasis-free survival was 86%. No previously listed adverse events were reported. Adverse events led to therapy discontinuation in only 11.7% of cases. ATT did not reduce patients' quality of life. In the subgroup analysis, the effectiveness of the combination of dabrafenib and trametinib after removal of distant metastases (equivalent to stage IV resectable) was found, in particular, the one-year relapse-free survival rate was 83%, and the one-year overall survival rate was 100%, which is comparable to these indicators for stage IIIB-D (72–86 and 78–100%, respectively). Conclusion. The effectiveness and favorable safety profile of the combination of dabrafenib and trametinib in ATT after radical surgical treatment was confirmed in a population of Russian patients with SM in the RW settings.

The article shows the criteria for differential ultrasound diagnosis of changes in regional lymph nodes in patients with high-risk skin melanoma