tbuckley/cabot-search huggingface dataset:
Intraperitoneal and intravenous paclitaxel plus S-1 versus intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis: Results from the multicenter, randomized, phase 3 DRAGON-01 trial.
Authors: Chao Yan, Zhongyin Yang, Zheng Shi, Sheng Lu, Min Shi, Mingming Nie, Jian Chen, Dan Wu, Yiping Mou, Yunyun Xu, Yanong Wang, Xiaowen Liu, Hui Cao, Jiayi Gu, Jiren Yu, Kai Liu, Xinchun Liu, Jun Zhang, Kai Yin, Zhenggang Zhu
Journal: Journal of Clinical Oncology (2025)

327 Background: The optimal chemotherapeutic regimen for gastric cancer with peritoneal metastasis remains undefined. We evaluated the efficacy and safety of intraperitoneal and intravenous paclitaxel plus S-1 (NIPS Group) versus paclitaxel plus S-1 (PS Group) in gastric cancer patients with peritoneal metastasis. Methods: In this multicenter, randomized, controlled, phase 3 trial, patients were recruited from 9 cancer centers in China. Eligible patients were aged 18~75 years with an Eastern Cooperative Oncology Group performance status of 0~1, histologically confirmed gastric adenocarcinoma, peritoneal metastases from gastric cancer requiring definitive diagnosis by laparoscopy, without gastric outflow tract obstruction and intestinal obstruction, no prior treatment with chemotherapy, radiation therapy, targeted therapy or immunotherapy. Eligible patients were randomly assigned (2:1) to receive either intravenous paclitaxel at 50 mg/m² and intraperitoneal paclitaxel at 20 mg/m² on days 1 and 8, along with oral S-1 at a dose of 80 mg/m² on days 1~14, or intravenous paclitaxel at 70 mg/m² on days 1 and 8, along with oral S-1 at 80 mg/m² on days 1~14. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all participants. A sample size of 238 patients was calculated to provide 80% power with a one-sided alpha of 0.1, accounting for a 10% dropout rate. Survival was analyzed using Kaplan-Meier curves and compared with the log-rank test. Cox regression was used for multivariate analysis. A P -value &lt; 0.05 was considered statistically significant. Results: From May 10, 2017, to March 9, 2022, 246 patients were screened and 222 were included in the modified intention-to-treat population, of whom 148 patients were assigned to the NIPS Group and 74 to the PS group. As of data cutoff (March 9, 2024), the median survival time was 19.4 months (95% CI, 17.1~22.9), in the NIPS group and 13.9 months (95% CI, 10.3~16.1) in the PS group (HR = 0.66; 95% CI 0.49 - 0.88; P = 0.005). The 1-year and 2-year overall survival rates were 69.6% and 37.2% in the NIPS group, compared to 54.1% and 20.3% in the PS group. The most common grade 3~4 adverse events were leukopenia (21.7% in the NIPS group, and 24.7% in the PS group) and neutropenia (19.9% in the NIPS group, and 23.4% in the PS group). No treatment-related deaths were reported. Conclusions: Intraperitoneal and intravenous paclitaxel plus S-1 significantly improved the overall survival compared to intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis, with manageable toxicity. Clinical trial information: ChiCTR-IIR-16009802.
A single institution retrospective study evaluating mitomycin dosing during chemoradiation in anal squamous cell carcinoma.
Authors: Jenny Gong, Emily Simon, J. Eva Selfridge, David L. Bajor, Emily Steinhagen, Melissa Amy Lumish, Sakti Chakrabarti, AMR Mohamed, Lauren E. Henke, Jennifer Anne Dorth, Amit Mahipal, Madison Conces
Journal: Journal of Clinical Oncology (2025)

7 Background: Mitomycin (MMC) is used concurrently during chemoradiation (CRT) treatment for non-metastatic anal squamous cell carcinoma (SCCA). The most effective dosing of MMC is not established, and due to concerns for tolerability, many have adopted a dose-reduction strategy. This study evaluates differences in treatment response and recurrence between MMC dosing in this setting. Methods: Demographics, age, smoking history, staging, and treatment history were collected for patients with non-metastatic SCCA treated with CRT from January 2011-September 2024 at a tertiary cancer center. Chi-square analyses compared categorical variables, and ANOVA tests were used to compare treatment response and recurrence between 3 MMC doses (12mg/m 2 x 1 dose with cap of 20mg, 10mg/m 2 x 2 doses, 10mg/m 2 x 1 dose). Results: There were 124 patients, 6 of whom were excluded due to lack of follow up. Of the 118 included, 70% were female, 16% Black, 3% Hispanic/Latino, and 58% current/former smokers. Median age was 61 years (31-98). Thirty-three (28%) pts were treated with MMC 12mg/m 2 , 71 (60%) with 10mg/m 2 x2 doses, and 14 (12%) with 10mg/m 2 x1 dose. Stage I included 18% of 12mg/m2, 7% of 10mg/m 2 x2 doses, and 7% of 10mg/m 2 x1 dose; stage II included 18% of 12mg/m2, 37% of 10mg/m 2 x2 doses, and 50% of 10mg/m 2 x1 dose; stage III included 64% of 12mg/m2, 56% of 10mg/m 2 x2 doses, and 43% of 10mg/m 2 x1 dose. A total of 39.7% were treated with MMC/capecitabine and 60.3% with MMC/fluorouracil. Complete response was achieved in 91% receiving the 12mg/m 2 , 75% receiving 10mg/m 2 x2 dose, and 71% receiving 10mg/m 2 x1 dose (p=0.13, Table 1). Using logistic regression with MMC dose, stage, age, and smoking status as independent predictors, the odds of achieving complete response were lower in 10mg/m 2 x2 doses (p=0.03) and 10mg/m 2 x1 dose (p=0.03) compared to 12mg/m 2 . Local, regional, or metastatic recurrence occurred in 15% of pts receiving 12mg/m 2 , 17% of 10mg/m 2 x2 doses, and 7% of 10mg/m 2 x1 dose. No significant difference was seen in local (p=0.52), regional (p=0.93), metastatic (p=0.87), or overall recurrence (p=0.65) between the MMC doses. Conclusions: Odds of achieving complete response was greater with 12mg/m 2 dosing. Local, regional, and metastatic recurrence were similar among the different MMC dosing cohorts. Differences in tolerance and side effects should be delineated to guide individualized dosing of MMC.
Effects of targeting CTMP on immunogenicity of MSI-L colon adenocarcinoma cells by metabolism and cell cycle modulation.
Authors: Cheng Gu, Rong He, Jie Gao, Rongjia Xie, Zhuqing Liu, Qing Xu
Journal: Journal of Clinical Oncology (2025)

246 Background: Regimen of metastatic colon cancer (mCOAD) is moving towards combination of immune checkpoint inhibitors (ICBs) and targeted therapy, however ICBs are rarely effective in MSI-L metastatic colon cancers, limiting options for backline treatments, new targeted therapy is on demand to improve immunogenicity of MSI-L mCOAD. As targeting fatty acid metabolism or cell cycle has shown potential in improving the efficacy of ICBs, our team focused on CTMP, a thioesterase (ACOT) family member, mainly modulates fatty acid β oxidation, meanwhile it binds to phosphorylation sites of AKT thus intervenes cell cycle, currently its role on immunogenicity of COAD is not clear. Methods: Correlation between CTMP and OS in MSI-L colon cancer patients was assessed by KM plotter in GEO database.11 Clinical samples of MSI-L colon cancer, who received a third-line treatment regimen of anti-PD-1 and fruquintinib, were collected then applied in immunofluorescence and western blot analyses to evaluate CTMP and MHC-I expression. In vitro, Lentiviral transfection of targeted genes were stably established,then applied in RNA-seq and metabolic assays. Proteomic analysis and co-IP were applied to explore CTMP-modulating pathway. In vitro, IFNγ was intratumorally injected. Results: KM curve showed CTMP was negatively correlated with OS in MSI-L COAD in GEO database. In clinical samples, lower CTMP expression and higher MHC-I expression were observed in partial response (PR) than progressive disease (PD) group. In vitro, CTMP-OE reduced MHC-I, increased AKT phosphorylation and immune checkpoints (PD-L1, IDO-1), promoted clone formation. Seahorse assay showed increased capacity of glycolysis and oxidative phosphorylation in CTMP-OE than vector. RNA-seq showed CTMP-OE reduced MHC-I augmentation under IFN-γ treatment, meanwhile glucose metabolism genes, ACOT family ,immune checkpoints were also up-regulated, indicating ACOT family related metabolism promotion and immunogenicity suppression of COAD. Proteomic analysis and co-IP assay indicated CTMP interacts REV7, a key mitotic regulatory protein. Enzyme activity assay showed REV7 negatively regulates CDK1. Furthermore, REV7-OE alone is capable to induce MHC I augmentation and G2 arrest, accordingly CTMP-KD enhanced REV7's negative modulation on CDK1,contributing to G2 arrest, that also augmented MHC I . In homologous mice tumor-bearing model, tumor shrinkage was observed in CTMP-KD/ REV7-OE group. CTMP-KD/ REV7-OE increases MHC I expression,CD8+ T cell infiltration under IFN γ intra-tumoral injection. Conclusions: In summary, our studies suggested that CTMP regulates the metabolism of colorectal cancer and intervenes MHC-I molecules expression, and targeting CTMP is potential in suppressing tumor cell cycle and promoting immunogenicity through its modulation on REV7.
Use of nucleotyping and tumor stroma ratio to predict prognosis in patients with resected intestinal-type gastric cancer.
Authors: Dan Sha, Jing Sun, Frank A. Sinicrope, Chunfang Tian, Haiyan Jing, Jinshen Wang, Qingchun Zhuang, Qian Yang, Wei Song
Journal: Journal of Clinical Oncology (2025)

483 Background: Heterogeneity exists in recurrence and survival among patients with intestinal-type gastric cancer (IGC). Nucleotyping is the alterations in chromatin organization. We sought to identify the prognostic utility of nucleotyping, tumor stroma ratio (TSR) and DNA ploidy in these patients. Methods: Radical resection of gastric carcinoma (&gt; 15 LNs removed) was performed in 283 patients (stage I, n=73; stage II, n=102; stage III, n=108) at our university hospital between 2010 and 2018. Automated image cytometry tools were used to quantitatively measure nucleotyping, TSR and DNA ploidy. Cutpoints of nucleotyping and TSR were 0.044 and 50%, respectively. Associations of these features with clinicopathological characteristics, time-to-recurrence (TTR) and cancer specific survival (CSS) were analyzed by univariate and multivariate analysis. Results: Among 283 patients, chromatin heterogeneity, high TSR and non-diploid were significantly associated with larger tumor size, higher T and N stage, and poorer TTR and CSS at 5 years. In a Cox multivariable analysis, nucleotyping and TSR were independently associated with TTR and CSS (P＜0.05) (Table). The top three contributors to TTR were N stage (33.9%), nucleotying (29.7%) and TSR (25.5%). The top three contributors to CSS were N stage (35.6%), nucleotying (29.7%) and TSR (18.0%). As a combined variable, the percent relative contribution of nucleotyping and TSR ranked first for TTR and CSS (56.0%, 50.0%), ahead of N stage (33.4%, 34.6%) and TILs (8.4%, 10.6%). Conclusions: Nucleotyping and TSR were each significantly and independently associated with TTR and CSS, and their combined variable was more strongly prognostic than either alone. Cox multivariable analysis of TTR and CSS. Features TTR HR (95%CI) TTR P value CSS HR (95%CI) CSS P value Tumor size (&gt;3cm vs ≤3cm) 1.10 (0.48-2.54) 0.83 0.77 (0.35-1.70) 0.56 T stage (T3-T4 vs T1-T2) 1.07 (0.46-2.49) 0.87 1.41 (0.53-3.76) 0.49 N stage (N2N3 vs N0N1) 2.84 (1.39-5.78) &lt;0.01 7.69 (3.37-17.55) &lt;0.01 Adjuvant Therapy (with vs without) 1.32 (0.72-2.40) 0.37 0.85 (0.48-1.52) 0.59 TB (high vs low) 1.29 (0.62-2.69) 0.50 1.61 (0.85-3.07) 0.15 TILs（low vs high） 1.73 (0.96-3.13) 0.07 1.90 (1.06-3.40) 0.03 Nucleotyping (Chromatin heterogeneous vs Chromatin homogeneous) 2.19 (1.21-3.99) 0.01 3.44 (1.96-6.03) &lt;0.01 TSR (high vs low) 2.12 (1.16-3.82) 0.01 2.51 (1.43-4.41) &lt;0.01 DNA ploidy (Non-diploid vs Diploid) 1.20 (0.55-2.63) 0.65 0.98 (0.44-2.15) 0.95 1 TTR, time-to-recurrence; 2 CSS, cancer specific survival.
Efficacy of plogosertib (CYC149462), a novel orally bioavailable PLK1 inhibitor, on patient-derived models of colorectal cancer.
Authors: Mohammad Zokaasadi, Wylie K Watlington, Divya Lakshmi Dayanidhi, Gabrielle Rupprecht, Shannon J. McCall, Brian Schwartz, Jason A. Somarelli, Shiaowen David Hsu
Journal: Journal of Clinical Oncology (2025)

209 Background: Colorectal cancer (CRC) is the third most common cancer in adults in the United States. Given the relative rapid cell division in cancer cells compared to most normal cells, drugs targeting mitosis and other cell cycle checkpoints are of interest in CRC treatment. One multi-tasking protein in cell division is polo-like kinase 1 (plk1). Plk1 is a serine threonine kinase that is highly expressed during mitosis and involved in a variety of functions, including spindle assembly, chromosome segregation, G2/M transition, and cytokinesis. Encouragingly, its expression is also significantly higher in CRC compared to normal mucosa, which makes it an attractive cancer-specific target in CRC. In this study, we sought to evaluate the efficacy of plogosertib (CYC149462), a novel plk1 inhibitor, in a series of preclinical models of advanced CRC. Methods: Fourteen CRC patient-derived organoids (PDOs) were generated from patients who underwent biopsy or resection for their primary or metastatic CRC under an IRB approved protocol at Duke University. Diagnosis of CRC is confirmed in PDOs using H&amp;E and IHC. Subsequently, PDOs were treated with plogosertib in a range of concentrations from 256pM to 100µM. Drug screens were performed for standard of care agents 5FU, oxaliplatin, and SN38. Viability was assessed with Cell-Titer Glo (CTG) 72 hours after treatment. Using a matched PDX, mice were treated with vehicle or 40 mg/kg daily of plogosertib via oral gavage for 2 weeks, 5 days per week. Cell cycle analysis was performed by flow cytometry, and localization of DNA during mitosis was done by fluorescence staining. Results: CRC PDOs were more sensitive to plogosertib (CYC149462) than 5FU, and oxaliplatin, with significantly lower IC 50 values (518.86±377.47nM for plogosertib vs. 38.87±45.63µM for 5FU, and 37.78±39.61µM for oxaliplatin respectively (ANOVA, P &lt; 0.05). Subsequently, we validated our findings in vivo using a matched PDX in which plogosertib treatment led to significant tumor growth inhibition compared to vehicle (t-test, p &lt; 0.05) without serious adverse effects. Furthermore, we showed that plogosertib induces dysfunction in alignment of chromosomes and subsequent G2/M cell cycle arrest (p &lt; 0.05). Conclusions: Together, our study shows that pharmacological inhibition of Plk1 using plogosertib represents a promising therapeutic approach for advanced CRC.
A retrospective study of the prognostic value of early induction of S-1 postoperative adjuvant therapy for pancreatic cancer.
Authors: Aki Yukutake, Tomohiko Adachi, Ayaka Kinoshita, Hajime Imamura, Takashi Hamada, Hajime Matsushima, Takanobu Hara, Akihiko Soyama, Susumu Eguchi
Journal: Journal of Clinical Oncology (2025)

689 Background: The usefulness of oral S-1 administration as adjuvant therapy (AC) after pancreatic cancer surgery has been demonstrated (1). Our study also suggested the importance of maintaining relative dose intensity or postoperative early induction (2). In a large Japanese data set, a comparison of induction before and after the postoperative 10 weeks showed a worse prognosis in the group which started 10 weeks after surgery (3). However, the number of patients of which early induction is possible are gradually increasing with recent improvements of surgical outcomes. In the present study, we retrospectively evaluated the survival benefit of AC which was started within 2 weeks after surgery. Methods: 129 patients with invasive pancreatic cancer who underwent radical surgery from January 2018 to May 2023 were enrolled in this retrospective study. The patients were divided into the following groups: 46 (36%) underwent induction within 2 weeks, 56 (43%) within 3-6 weeks, 13 (10%) after 7 weeks, and 14 (10%) without AC (4 with low renal function, 4 with deteriorating physical condition after surgery, 4 with not desired, and 2 with comorbid disease treatment). The background of each group was as follows (Described in the following order; induction within 2 weeks after surgery: 3-6 weeks: after 7 weeks: without AC), age 71: 71: 71: 78 (n.s.), pancreatic head cases 52: 68: 69: 50% (n.s.), BR cases 35: 23: 8: 21% (n.s.), NAC performed 86: 38: 15: 29% (p &lt; 0.001), preoperative CEA ≥ 5.0ng/ml 24: 23: 8: 21% (n.s.), preoperative CA19-9 ≥ 37U/ml 48: 52: 54: 64% (n.s.), PV/SMV reconstruction 20: 16: 31: 14% (n.s.), postoperative complications (Clavien Dindo ≤3) 0: 16: 31: 43% (p &lt; 0.001), Pathological stage 2 or higher 83: 65: 77: 79% (n.s.). Results: The need for reduction of S-1 dosage was 87: 89: 92% of the patients (n.s.), and the 6-month completion rate was 70: 71: 61% (n.s.). Median overall survival duration in each group was as follows: not reached: 49.5: 35.5: 48.6 months, and 1-year postoperative recurrence-free survival was 73: 66: 45: 71%, median recurrence free survival time was 34.0: 20.8: 10.3: 12.1 months, and induction within 2 weeks after surgery group significantly improved the recurrence-free survival in comparison with the group of after 7 weeks (p &lt; 0.05). No significant factors were detected in multivariate analysis. Conclusions: These results suggest that early induction of AC as a result of improvement of surgical outcomes would contribute to postoperative recurrence-free survivals. 1. Uesaka et al, Lancet, 2016. 2. Matsushima et al. Anticancer Res, 2022. 3. Tomimaru et al, J Gastroenterol, 2023.
Outcomes of patients with peritoneal-limited metastatic gastric cancer (PLGC) undergoing bidirectional (BD) chemotherapy cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC).
Authors: Evelyn Yi Ting Wong, Shun Zi Liong, Claramae Chia, Johnny Chin-Ann Ong, Hock Soo Ong, Weng Hoong Chan, Chin Hong Lim, Eugene Kee Wee Lim, Jeremy Tian Hui Tan, Glenn Chua, Kennedy Yao Yi Ng, Chiew Woon Lim, Justina Yick Ching Lam, Lee Lian Chew, Matthew C.H. Ng
Journal: Journal of Clinical Oncology (2025)

328 Background: The prognosis of PLGC patients (pts) is poor with standard systemic therapy. PLGC pts who undergo CRS after BD chemotherapy (chemo) demonstrate prolonged survival. We retrospectively analysed the outcomes of pts who underwent BD chemo followed by CRS and HIPEC in a single institution, stratifying by peritoneal carcinomatosis index (PCI) and chemo regimen. Methods: PLGC pts who received BD chemo between January 2016 to September 2023 were enrolled and consented for data collection. BD chemo was either 3 weekly paclitaxel (PTX) (50mg/m2), S-1 (80mg/m2) and IP PTX (20mg/m2) or capecitabine (2g/m2), oxaliplatin (100mg/m2) (CAPOX) and IP PTX (40mg/m2). HIPEC utilised cisplatin 50mg/m2 at 40 for 60 minutes. Trastuzumab and nivolumab were given selectively. Pts without radiological progression after 24 weeks of BD chemo, with PCI7 and potential for complete resection underwent CRS including D2 gastrectomy and HIPEC. Post-resection, BD chemo was stopped. Survival was analysed by Kaplan Meier curves, adverse events (AEs) by CTCAE v5.0 and response by independent radiological review. Results: 34 pts were enrolled with median follow-up of 26.9 months (m). Median (range) age was 51 (17 – 79) and median PCI 12 (0-29). 52.9% were female, 8.8% had Cy1 only disease and 38% had prior gastrectomy. 3 out of 6 pts with evaluable disease had partial response. Median progression-free survival and overall survival (mOS) was 9.1m and 16.5m respectively. 7 pts (20.6%) underwent CRS with median (range) PCI of 1 (0-15.0). mOS in CRS vs non-CRS pts was 23.8m vs 14.6m (p=0.4); PCI &lt;7 vs PCI ≥7 was 23.8m vs 14.6m (p=0.63); and CAPOX vs S1/PTX systemic chemotherapy was 23.9m vs 14.6m (p=0.29) respectively. Peritoneal cytology negativity increased from 25.8% to 86.4% after BD chemo. Peritoneal lesions biopsied post-BD chemo showed no tumour cells in 64% of cases. There was no treatment-related mortality. 1 pt had IP port removal due to complications. The commonest grade 3 AE was neutropenia (14.7%). Biomarker analysis is currently being performed. Conclusions: BD chemo CRS HIPEC was well tolerated with longer survival in patients undergoing CRS. Evaluation of tumour using PCI post-BD chemo may be sub-optimal.
PK/PD analyses of circulating tumor DNA (ctDNA) in patients with metastatic colorectal cancer (mCRC) treated with telisotuzumab adizutecan (ABBV-400).
Authors: Ibrahim Abdelgawad, Athanasios Vasilopoulos, Martha Raluca Neagu Aristide, Kevin Jay Freise, Apurvasena Parikh, Carla Biesdorf de Almeida
Journal: Journal of Clinical Oncology (2025)

233 Background: Telisotuzumab adizutecan (ABBV-400) is an antibody drug conjugate (ADC) consisting of a c-Met targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload adizutecan. The ongoing first in human phase 1 trial (Study M21-404; NCT05029882) shows that ABBV-400 has encouraging radiographic response and ctDNA molecular response (MR) as monotherapy in patients with advanced solid tumors, including mCRC. Herein, correlation between ABBV-400 exposures and % change in ctDNA from baseline and PK/PD analyses using MR are presented for mCRC patients. Impact of c-MET expression and MET amplification ( MET -amp) status on exposures was also evaluated. Methods: Analyses utilized preliminary data in mCRC patients (N=122) from study M21-404 where subjects were treated with ABBV-400 (1.6 – 6.0 mg/kg Q3W). Serial PK samples were collected in cycles 1 (C1) and 3 (C3) and sparse samples across other cycles. C1 exposure metrics (C max , C avg , and C trough ) for both ABBV-400 conjugate and unconjugated payload were obtained by non-compartmental PK analysis. Baseline and C3 day 1 plasma samples were collected and analyzed using the Guardant INFINITY assay for biomarker analysis. ctDNA (circulating tumor fraction [cTF]) was estimated based on 1) variant allele frequency of somatic mutations in a 74 gene panel and 2) methylation signals across targeted regions of the Guardant INFINITY methylation panel. MR was defined as a 50% decrease in cTF from baseline. PK/PD correlations with % change in cTF at C3 and MR at C3 were evaluated. c-Met protein expression was assessed by IHC (VENTANA MET SP44 RxDx Assay) and MET -amp status was based on available local testing results and retrospective ctDNA testing. Results: Higher exposures of ABBV-400 conjugate and payload (primarily C avg for both analytes and C max for conjugate) correlated with greater decrease in % change in cTF at C3 from baseline, as assessed by the 74 gene panel (N =66) or methylation panel (N=74). PK/PD analysis showed that higher exposure was strongly correlated with higher probability of MR (n=66-74, nominal p &lt; 0.05). ABBV-400 conjugate and payload exposures were comparable across c-Met expression H-score (range 9 – 295), cut-offs (≥90% with 1+ intensity, ≥50% with 2+, ≥10% with 3+, ≥25% with 3+, and ≥50% with 3+), and MET -amp status. Conclusions: Exposure-response analyses have previously shown correlation between ABBV-400 conjugate exposures and probability of efficacy (objective response rate) as well as safety in mCRC subjects. The current PK/PD analyses demonstrate that higher ABBV-400 conjugate and payload exposures are also correlated with liquid biopsy data, i.e., ctDNA and MR based on ctDNA. c-MET expression and MET-amp did not have impact on ABBV-400 exposures. Clinical trial information: NCT05029882 .