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Axially Chiral Bifluorenylidene Radical Anions with Long Spin–Lattice Relaxation Times at Room Temperature in Fluid Solution

Understanding attenuated positive facial expression in depressed women: central role of dorsal raphe network alterations and associated serotonin transporter methylation

Disitamab vedotin (DV) plus toripalimab (Tor) and chemotherapy (Chemo)/trastuzumab (Tra) for first-line (1L) HER2-expressing locally advanced or metastatic (la/m) gastric cancer (GC): Updated results from the RC48-C027 trial.

LBA4026 Background: For patients (pts) with HER2-high (defined as IHC 3+, or IHC 2+/FISH+ based on Chinese CSCO GC guidelines) GC, current 1L therapy consisting of trastuzumab combined with pembrolizumab and chemotherapy offers limited efficacy. For pts with HER2-intermediate/low (defined as IHC 1+, or IHC 2+/FISH- as per Chinese guidelines) GC, no HER2-targeted precision treatment is available. Previous analysis of the RC48-C027 randomized phase 2 part showed notable objective response rates (ORRs): 82.4% with DV + Tor + Tra in HER2-high GC; 72.0% with DV + Tor + CAPOX (oxaliplatin and capecitabine) in HER2-intermediate/low GC, and lowering the CAPOX dose showed improved safety while maintaining efficacy (ORR: 71.4%) (Shen et al. J Clin Oncol. 2025). We report updated results with extended follow-up, including tumor response, mature progression-free survival (PFS), and overall survival (OS) data. Methods: Pts with HER2-high, untreated, la/m gastric/gastroesophageal junction (G/GEJ) cancer were randomized at a ratio of 1:1:1 to receive DV + Tor + CAPOX (DTC), or DV + Tor +Tra (DTT), or Tor + Tra + CAPOX (TTC). For HER2-intermediate/low, untreated, la/m G/GEJ cancer, pts were randomized at 1:1 to receive DV + Tor + CAPOX (DTC), or Tor + CAPOX (TC) in Stage 1; to enhance the overall tolerability, Stage 2 was initiated and randomized pts at 1:1:1 to receive DV + Tor + dose-reduced CAPOX (DTCr), or dose-reduced DV + Tor + dose-reduced CAPOX (DrTCr), or Tor + CAPOX (TC). The primary endpoint was ORR; secondary endpoints included PFS, duration of response (DoR), OS, and safety. Results: By the data cutoff (Jan 16, 2026), durable responses, a clinically meaningful improvement in PFS, and a favorable trend in OS were observed with DTT and DTCr. No new safety signals emerged. More outcomes are detailed in the Table. Conclusions: With extended follow-up, DTT and DTCr demonstrated sustained and clinically meaningful efficacy as 1L treatments for HER2-high and HER2-intermediate/low G/GEJ cancer, respectively. These findings warrant further confirmation in phase 3 trials. Clinical trial information: NCT05980481 . HER2-high pts HER2-intermediate/low pts / Stage 1 Stage 2 DTC (n=18) DTT (n=17) TTC * (n=16) DTC (n=25) TC * (n=23) DTCr (n=14) DrTCr (n=15) TC * (n=16) OS follow-up (m), median 23.3 21.3 16.6 Confirmed ORR ^ , % (95% CI) 66.7(41.0-86.7) 82.4(56.6-96.2) 68.8(41.3-89.0) 75.0(53.3-90.2) 47.8(26.8-69.4) 76.9(46.2-95.0) 66.7(38.4-88.2) 60.0(32.3-83.7) DoR (m), median NR NR 13.9 12.4 10.0 NR 12.9 10.6 PFS (m), median (95% CI) NR(8.2-NR) 18.0(8.5-NR) 13.8(3.1-19.6) 9.9(5.8- NR) 7.2(5.4-11.3) 9.5(4.8-NR) 12.7(2.4-NR) 9.9(2.8-13.4) HR 0.39 0.58 / 0.58 / 0.59 0.70 / OS (m), median NR NR 21.6 16.9 18.7 NR NR NR HR 0.63 0.43 / 1.04 / 0.61 0.95 / * Control arm. ^ In pts with ≥1 post-baseline tumor assessment. m, months; NR, not reached; HR, hazard ratio.

Label-Free Imaging of Single Proteins and Binding Dynamics via Deep Learning-Enhanced Plasmonic Scattering Microscopy

Effects of an indole chemical, mitochonic acid 5, in a mouse model of mitochondrial disease onset

Low-dose pembrolizumab with chemotherapy in advanced NSCLC: A phase 3 randomized trial.

LBA1510 Background: Pembrolizumab plus Platinum doublet chemotherapy is the standard of care for advanced non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGAs). Access to Pembrolizumab & other immune checkpoint inhibitors (ICIs) is limited due to their cost. There is evidence to suggest that ICIs are efficacious at lower doses. The efficacy of low-dose Pembrolizumab & Nivolumab has been demonstrated in phase 3 trials in other settings. There is no randomised data for low-dose Pembrolizumab in advanced NSCLC. We conducted this study to evaluate the efficacy of low-dose Pembrolizumab in this setting. Methods: This is a phase 3 open-label randomised trial with a superiority design that included patients with advanced NSCLC without AGAs. Participants aged ≥18 years & ECOG PS ≤2 were randomised 1:1 to receive Platinum-doublet chemotherapy (Arm A) or Platinum-doublet chemotherapy with low-dose Pembrolizumab (Arm B). Chemotherapy included Pemetrexed/Paclitaxel plus Carboplatin/Cisplatin for 4-6 cycles. Pembrolizumab 50 mg was administered every 3 weeks for the first 4 doses & then every 6-weeks. Treatment was continued until disease progression or intolerable side effects. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), safety, & QoL. The Kaplan-Meier method & the Cox proportional hazards model were used for analysis. Results: 380 participants were randomised,187 to Arm A &193 to Arm B. Participants were predominantly male (76.1%), with a median age of 57 yrs; 61.1% had ECOG PS 0-1, 38.9% had ECOG PS 2, 54.5% were former/current smokers. The most common histological subtype was adenocarcinoma (68.4%). Brain metastases were present in 27.1%. The median follow-up was 13 mos (95% CI 12.2-14.1). The median OS was 10.47 mos (95% CI 8.38-12.56) in Arm A and 13.46 mos (95% CI 11.71-15.22) in Arm B; HR 0.72 (95% CI 0.54-0.95) (p=0.020). The 1-year OS was 44.4% (95% CI 37.2-53) in Arm A and 57.32% (95% CI 44.93-65.79) in Arm B. The median PFS was 4.70 mos (95% CI 4.06-5.34) in Arm A and 6.73 mos (95% CI 5.51-7.96) in Arm B, HR 0.70 (95% CI 0.56-0.89), p=0.003. The 1-year PFS was 18.79% (95% CI 13.59 - 25.99) in Arm A and 26.72% (95% CI 20.23 - 35.29) in Arm B. Grade 3 or higher neutropenia was significantly higher in Arm B (28%) compared to Arm A (17.6%), p=0.02. There was no difference in the incidence of grade 3 or higher anemia or thrombocytopenia. Grade 3 or higher immune-related pneumonitis was seen in 3.1% in Arm B. Conclusion: The addition of low-dose Pembrolizumab to chemotherapy significantly improved overall survival and progression-free survival in patients with advanced NSCLC. There were no new safety signals. This regimen will improve access to ICIs in resource-limited settings. Clinical trial information: CTRI/2023/08/056715.

Proton-Feeding Dual-N Claw Sites in a Copper-Covalent Organic Framework Promote Hydrogenation Kinetics for Electrocatalytic Nitrate Reduction

Blockchain-enhanced federated learning for IoT security and privacy using the GSR-C2N model

Abstract The rapid proliferation of Internet of Things devices has intensified the demand for security, privacy-preserving, and scalable machine learning solutions. Federated Learning (FL) supports the decentralized training of models across distributed devices without transporting raw data, whereas blockchain provides a trusted, transparent mechanism for integrity and reaching consensus. The paper explains an FL framework that incorporates blockchain technology, based on the GSR-C2N model for identifying crypto-mining malware. It is demonstrated that the system’s feature extraction and optimization processes are optimized to address security problems in IoT by utilizing blockchain to verify model updates and build trust and privacy. The given structure has demonstrated superiority to the current practices. This model was 96.85% accurate and 97.51% specific on the crypto-mining malware data set using 10-fold cross-validation, making it applicable to smart healthcare and smart city applications with IoT-based systems. In addition, when combined with regulatory compliance, homomorphic encryption can strengthen data and privacy management, underscoring the model’s effectiveness in advanced IoT systems.

Efficacy and safety results from EMERALD-3: A phase 3, randomized study of tremelimumab plus durvalumab with or without lenvatinib combined with transarterial chemoembolization (TACE) in participants (pts) with unresectable embolization-eligible hepatocellular carcinoma (eeHCC).

LBA4000 Background: TACE, a global standard of care (SoC) for unresectable eeHCC, induces a tumor immune response. STRIDE (Single Tremelimumab [T] Regular Interval Durvalumab [D]) has shown OS benefit at 6-year follow-up and is a SoC for unresectable advanced HCC. We report preplanned analyses from EMERALD-3 (NCT05301842), which combined STRIDE ± lenvatinib (L) with TACE. Methods: Eligible pts (≥18 yr) with confirmed eeHCC were randomized 1:1:1 to STRIDE (T 300 mg + D 1500 mg on Day 1 then D 1500 mg Q4W) + L (8 or 12 mg QD) + TACE; STRIDE + TACE; or TACE until reaching 175 pts/arm. Randomization continued 1:1 until STRIDE + L + TACE and TACE reached 275 pts/arm. D and L continued for ≤36 months (mo), until disease progression, unacceptable toxicity, or withdrawn consent. Pts were stratified by region, any prior palliative embolization, and baseline tumor burden by the Up-To-Seven criteria. The primary endpoint was PFS for STRIDE + L + TACE vs TACE by a stratified Cox proportional hazards model and stratified log-rank test. Key secondary endpoints were OS (STRIDE + L + TACE vs TACE), and PFS plus OS (STRIDE + TACE vs TACE). Results: As of Feb 23, 2026, 293 pts were randomized to STRIDE + L + TACE, 175 to STRIDE + TACE, and 292 to TACE. Baseline characteristics were broadly balanced across arms. STRIDE + L + TACE showed a statistically significant improvement in PFS vs TACE (HR, 0.70; 95% CI, 0.57–0.86; p=0.0007), and a positive OS trend (HR, 0.84; 95% CI, 0.65–1.09; p=0.1814). STRIDE + TACE also improved PFS (HR, 0.71; 95% CI, 0.56–0.91) and OS (HR, 0.70; 95% CI, 0.51–0.95) vs TACE. STRIDE ± L + TACE showed higher 24-mo OS rate vs TACE (Table). The incidence of treatment-related AEs of maximum grade 3/4 was 62.7% for STRIDE + L + TACE, 48.6% for STRIDE + TACE, and 18.6% for TACE. Conclusions: STRIDE + L + TACE significantly improved PFS vs TACE. At interim analysis, with ≤45% maturity, a positive trend for OS with STRIDE ± L + TACE vs TACE was observed. STRIDE + TACE also improved PFS vs TACE. AEs were aligned with known safety profiles of individual therapies. The EMERALD-3 results support STRIDE ± L + TACE as potential new treatment option in unresectable eeHCC. Clinical trial information: NCT05301842 . STRIDE + L + TACE(n=293) TACE(n=292) STRIDE + L + TACE(n=first 175) STRIDE + TACE(n=175) TACE (n=first 175) PFS (95% CI) HR 0.70 (0.57–0.86)p = 0.0007* 0.71 (0.56–0.91) † Maturity 64%* 75% † Median, mo 13.0 (12.2–16.7)* 9.8 (8.0–11.4)* 13.1 (11.0–17.7) † 12.9 (10.2–15.9) † 8.1 (6.5–10.2) † OS (95% CI) HR 0.84 (0.65–1.09) p = 0.1814 † 0.70 (0.51–0.95) † Maturity 40% † 45% † Median, mo 39.5 (34.1–NC) † 34.7 (28.8–NC) † 39.5 (32.6–NC) † NC (37.7–NC) † 32.9 (24.1–43.2) † 24-mo rate, % 66.9 (61.0–72.2) † 61.5 (55.4–67.0) † 67.8 (60.3–74.2) † 68.0 (60.4–74.5) † 57.8 (50.1–64.9) † NC, not calculable. Based on Data cutoff 1: *Sep 2, 2025; 2: † Feb 23, 2026.

Fe(porphyrin)-Catalyzed Alkene Epoxidation with NaOCl: A Practical Small- and Large-Scale Alternative to <i>m</i> CPBA

Spatiotemporal cross-attention hybrid network for weather forecasting in complex terrain

Durvalumab in Combination With Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: Long-Term Analysis From the GeparNuevo Trial

The phase II GeparNuevo trial investigated whether adding durvalumab to neoadjuvant chemotherapy (NACT) only in patients with early triple-negative breast cancer cT1b-cT4a-d would improve pathologic complete response (pCR) rate and patient survival. Hundred and seventy-four patients were randomly assigned to receive durvalumab or placebo concurrently with nab-paclitaxel once per week and followed by dose-dense epirubicin and cyclophosphamide. With 86.4 months of median follow-up compared with the previously reported 43.7 months, durvalumab showed sustained significant improvements in long-term outcomes as defined by STEEP compared with placebo regarding not only invasive disease-free survival (iDFS; hazard ratio [HR], 0.56 [95% CI, 0.32 to 0.99]; stratified log-rank P = .0431), but also distant disease-free survival (DDFS; HR, 0.41 [95% CI, 0.21 to 0.80]; P = .0069) and overall survival (OS; HR, 0.33 [95% CI, 0.14 to 0.79]; P = .0085). All analyses were stratified by stromal tumor-infiltrating lymphocytes (sTILs) at baseline (low [≤10%], intermediate [11%-59%], high [≥60%]). In exploratory subgroup analysis, patients with nodal involvement at baseline demonstrated a greater iDFS benefit (HR, 0.33 [95% CI, 0.144 to 0.771]; P = .01; P interaction = 0.045). sTILs in residual disease (RD) could be assessed in 39/71 patients without pCR. Post hoc analyses by sTILs high (&gt;10%) versus low (≤10%) in RD showed estimated 7-year iDFS rates of 92.3% (95% CI, 56.6 to 98.9) and 51.4% (95% CI, 29.2 to 69.7), respectively. Hence, adding durvalumab to dose-dense NACT without adjuvant continuation of checkpoint inhibition improved long-term survival outcomes, irrespective of the extent of pathologic response. This underscores the necessity to re-evaluate the adjuvant continuation of checkpoint inhibition.

A Temporal Decoupling Strategy for Controlled Synthesis of 2D TbOBr and Moiré Superlattices

Gingival expression of MMP-1, MMP-9, and HBD-3 in healthy individuals and patients with moderate to severe chronic periodontitis

MATRiX: A randomized phase II trial of tuvusertib (ATR inhibitor) with or without avelumab in advanced anti-PD(L)-1 refractory Merkel cell carcinoma.

LBA9514 Background: Advanced Merkel cell carcinoma (MCC) often responds to anti-PD-(L)1, but patients (pts) with immune checkpoint inhibitor (ICI)-refractory disease have poor outcomes and few therapy options. MCC has defects in G1 checkpoint control, proliferates rapidly, and is reliant on S/G2 checkpoints such as ATR (ataxia telangiectasia mutated and Rad3-related). Inhibiting ATR can promote immunogenic cell death. MATRiX (MCC refractory to immunotherapy treated with ATR inhibitor ± avelumab) is a multicenter, NCI-sponsored, randomized, open-label phase II trial evaluating tuvusertib, an ATR inhibitor, alone (Arm 1) or in combination with avelumab (Arm 2) in anti-PD-(L)1-refractory MCC, NCT05947500. Methods: Pts were randomized 1:1 using a permuted-block design. Arm 1 received tuvusertib 180 mg PO on days 1-14 of each 21-day cycle. Arm 2 received tuvusertib as in Arm 1, plus avelumab 1600 mg IV every 21 days. Pts with disease progression in Arm 1 were eligible to cross over to Arm 2. The planned sample size (N=50; 25 per Arm) provided &gt;80% power to observe a statistically significant (1-sided level of 0.15) difference in the primary endpoint, progression-free survival (PFS), assuming a hazard ratio of 0.5. Secondary endpoints were overall response rate (ORR), duration of response, and overall survival (OS). Data cutoff: January 20, 2026. Results: From 5/2024 to 9/2025, 35 subjects (median age 73) received therapy: Arm 1, n=10; Arm 2, n=25. One pt was deemed ineligible post-randomization and excluded from all analyses. 18 pts (53%) had primary ICI-refractory disease, and 22 (65%) had ≥2 prior systemic therapies. Arm 1 met prespecified futility criteria (0/10 responses) and was closed early. No objective responses were observed among 4 pts who crossed over to Arm 2. Among 24 eligible pts in Arm 2, 1 complete and 4 partial responses [ORR 20.8% (95% CI: 7.1-42.2%)] were observed, including 4 primary and 1 acquired ICI-resistant cases. 4 of 5 responders remained progression-free at cutoff (182-273 days from treatment initiation); 1 relapsed at 479 days. One-year estimates were PFS 0% (Arm 1) and 26.4% (Arm 2; 95% CI: 10.8-45.1%) and OS 29.2% (Arm 1; 1.5-69.8%) and 36.5% (Arm 2; 7.8-67.2%), respectively. Grade ≥3 treatment-emergent adverse events occurred in 80% of pts in Arm 1 and 58% in Arm 2; the most common were lymphopenia (20% vs 21%), anemia (50% vs 17%), fatigue (20% vs 17%), pain (10% vs 17%), and infection (0% vs 17%). Safety profiles were consistent with previous reports for these agents. Conclusions: Tuvusertib with avelumab demonstrated antitumor activity in anti-PD-(L)1-refractory MCC, inducing durable clinical benefit in ICI-resistant metastatic pts with limited salvage options. No signal of anticancer efficacy was observed with ATRi monotherapy. These findings warrant further investigation of ATRi in combination with immunotherapy in ICI-refractory MCC. Clinical trial information: NCT05947500 .

Mathematical analysis of photoreceptor changes in conditions of separation from the underlying retinal pigment epithelium

Palbociclib plus tamoxifen ± goserelin in women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer (BC): PATHWAY, an Asian international double-blind randomized phase 3 trial—Final overall survival (OS) analysis.

LBA1018 Background: In Asia, BC incidence is increasing and peaks before menopause; tamoxifen is commonly used for pre/perimenopausal BC. However, tamoxifen was not approved for use in combination with CDK4/6 inhibitors in many countries. PATHWAY previously showed significantly improved progression-free survival (PFS) for palbociclib plus tamoxifen (± goserelin) at the primary analysis (data cut-off 15 Sep 2022) with immature OS. Here, we report updated PFS and final OS. Methods: This phase 3 trial was conducted in Japan, Korea, Taiwan, and Singapore (NCT03423199). Eligible patients were women with locally advanced or metastatic HR-positive, HER2-negative BC who were candidates for 1st- or 2nd-line tamoxifen-based endocrine therapy and had not received a prior CDK4/6 inhibitor. Patients were randomized 1:1 to receive palbociclib (125 mg daily, days 1–21 of a 28-day cycle) or placebo, each with tamoxifen 20 mg daily. Pre/perimenopausal patients also received goserelin. Randomization was stratified by line of therapy and menopausal status. Investigator-assessed PFS (primary endpoint) and OS were analyzed using Kaplan–Meier methods and compared using a stratified log-rank test with 1-sided p values; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a stratified Cox proportional hazards model. Results: 184 patients were randomized (Feb 2018–Jul 2019) at 22 sites. Overall, 28.3% were pre/perimenopausal and 71.7% postmenopausal; 60.9% received study treatment as 1st-line and 39.1% as 2nd-line endocrine therapy. At the end of study in October 2025, 154 PFS events and 105 deaths occurred. Updated PFS remained significantly improved with palbociclib plus tamoxifen vs placebo plus tamoxifen (HR 0.594; 95% CI, 0.427–0.825; P &lt; 0.001), with median PFS 24.4 months (95% CI, 13.1–32.4) vs 11.1 months (95% CI, 7.4–14.6), respectively. PFS benefit was observed regardless of menopausal status (pre/perimenopausal: HR 0.343; 95% CI, 0.175–0.675; postmenopausal: HR 0.697; 95% CI, 0.479–1.012). Final OS also favored palbociclib plus tamoxifen (HR 0.772; 95% CI, 0.525–1.134; P = 0.093), with median OS 71.7 months (95% CI, 57.1–not estimable) vs 62.0 months (95% CI, 49.9–73.1); OS results were consistent across menopausal subgroups (pre/perimenopausal: HR 0.747; 95% CI, 0.339–1.647; postmenopausal: HR 0.772; 95% CI, 0.497–1.198). Palbociclib plus tamoxifen was generally well tolerated; adverse events were manageable with dosing interruptions/dose reductions, and no new safety findings. Conclusions: With longer follow-up, palbociclib plus tamoxifen (± goserelin) provided durable PFS benefit and a favorable OS trend with manageable safety, supporting this regimen as an effective option regardless of menopausal status. Clinical trial information: NCT03423199 .

<i>Operando</i> Imaging of Adsorbate-Charge Cooperative Reconstruction into Terminal Active Co–OH Sites

Exact noise influenced soliton solutions of a high-order stochastic nonlinear Schrödinger equation with weak nonlocal nonlinearity in a non-Kerr medium

Abstract In this study, a high-order stochastic nonlinear Schrödinger equation (SNLSE) with weak non-local nonlinearity in a non-Kerr law medium is investigated. This model describes the propagation of solitons in nonlinear optical fibers under stochastic effects and higher-order nonlinear interactions. To obtain analytical solutions, a wave transformation together with symbolic computations and the modified extended mapping method (MEMM) is employed. As a result, various exact wave solutions are derived, including bright, dark, singular, periodic, and rational-type solitons. A rigorous linear stability analysis is performed using perturbation theory and dispersion relation analysis, demonstrating that the obtained solutions are linearly stable under small perturbations. The graphical behavior of the solutions under different parameter settings is also presented to illustrate the dynamical characteristics of the model. The results confirm the efficiency and reliability of the proposed method in handling high-order stochastic nonlinear Schrödinger-type equations.

A multicenter, randomized, controlled, open-label, phase II trial of autologous tumor-infiltrating lymphocytes (GC101 TIL) in patients with advanced melanoma.

LBA9509 Background: Tumor-infiltrating lymphocyte (TIL) therapy is effective in advanced melanoma but hampered by toxicity from high-dose IL-2 and lymphodepletion (cyclophosphamide/fludarabine). We explored a modified TIL therapy (GC101) featuring an IL-2-free protocol and a low-intensity preconditioning regimen. This phase II study evaluates the modified GC101 TIL therapy in anti-PD-1-resistant melanoma. Methods: MIZAR-003 (NCT06703398) is a multicenter, phase II, randomized, open-label trial across 25 sites in China enrolling advanced melanoma patients resistant to PD-1 antibodies. Key eligibility: ECOG 0–1, adequate organ function. Exclusion: uveal melanoma, prior cellular therapy within 6 months. A total of 98 patients will be randomized 1:1 to Arm A (GC101 TIL) or Arm B (investigator-choice chemotherapy). GC101 therapy consists of tumor resection, low-intensity preconditioning (cyclophosphamide 20 mg/kg/d, pre-infusion d -5 to- 3; hydroxychloroquine 600 mg, pre-infusion d -5), followed by infusion of IL-2-free TIL and sintilimab (100 mg at infusion, then 100 mg Q6W × 4). Patients in Arm B with IRC-confirmed disease progression may cross over to receive GC101 TIL. The primary endpoint is IRC-assessed PFS per RECIST v1.1. Secondary endpoints include IRC-assessed ORR, CR rate, DOR, and OS; investigator-assessed ORR, PFS, CR rate, DOR, and PFS2; and safety. Results: In this exploratory interim analysis (70% of expected events), 84 patients were randomized (Arm A: 44; Arm B: 40) between 02/2025 and 01/2026, with a median follow-up of 5.2M (range 1.1-12.0). Baseline characteristics were balanced. As assessed by IRC, Arm A significantly improved mPFS (4.1M [95% CI 2.8–5.6] vs 1.6M [95% CI 1.3-4.0]; HR 0.53 [95% CI 0.30-0.94], p=0.0310), ORR (45.2% vs 5.4%; p=0.0018), and DCR (80.6% vs 43.2%; p=0.0017). OS data are immature. In mucosal melanoma (n=6 per arm), mPFS was not reached vs 1.3M, with DCR of 100.0% vs 33.3%. Grade ≥3 treatment-related AEs (TRAEs) occurred in 36.8% (Arm A) vs 27.5% (Arm B); treatment-related SAEs in 13.2% vs 7.5%. No new safety signals were observed, and no TRAEs led to treatment discontinuation or death. Conclusions: GC101 TIL significantly improved PFS and ORR versus investigator-choice chemotherapy in anti-PD-1-resistant melanoma, with manageable safety, supporting its potential as a new later-line therapy. Clinical trial information: NCT06703398 .