tbuckley/cabot-search huggingface dataset:
Abstract CT120: First in human phase 1 dose escalation and expansion clinical trial to evaluate the safety, pharmacokinetics and antitumor activity of intravenous AROG4-01 in patients with advanced solid tumors
Authors: Vicente Valentí, María Jove, Cinta Hierro, Víctor Moreno, Marta Gil-Martin, Emiliano Calvo, Ernest Nadal, Sonia Macia, Carme Plasencia
Journal: Cancer Research (2025)

Abstract AROG4-01 is a synthetic compound with a first-in-class mechanism of action, targeting complex secondary structural elements in mRNA, including G-quadruplexes (G4s). These secondary nucleic acid structures, characterized by Hoogsteen base pairing, play pivotal roles in gene regulation and are abundant in cancer cells due to their high proliferation rates and dysregulated gene expression patterns. By binding to G4s present in untranslated regions, AROG4-01 modulates gene expression at the post-transcriptional level, reducing tumor growth and survival. Preclinical studies have demonstrated that AROG4-01 achieves significant antitumor activity, inhibiting cancer cell proliferation, with a strong effect of the compound on inhibit colony formation, evidencing the capacity of AROG4-01 to prevent the long-term survival and proliferation of cancer cells. This activity has been validated in vivo across multiple solid cancer models. Methods: This study (NCT06652529, EudraCT2024-517569-18) is an open label, Phase 1 dose escalation trial with two expansion cohorts to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of AROG4-01. The study consists of two parts. Part A is a dose escalation that will include 8-20 patients with advanced solid tumors, covering up to 6 dose levels with the primary objective of determining the safety and tolerability of AROG4-01 and defining an appropriate recommended phase 2 dose (RP2D) for further evaluation in part B. The study will start with an accelerated-titration dose escalation scheme enrolling one evaluable patient per cohort for the first 2 dose levels followed by a classic 3+3 design. Part B is a dose expansion, with two cohorts of ten patients: one cohort of patients with advanced mesothelioma (cohort 1) and a second cohort of patients with other solid tumors (cohort 2). Serum samples collected from patients enrolled in part A when receiving the first IMP dose during the first treatment cycle will be used to assess the PK of AROG4-01. Three sites in Spain are expected to participate. Recruitment is not yet open. Citation Format: Vicente Valentí, María Jove, Cinta Hierro, Víctor Moreno, Marta Gil-Martin, Emiliano Calvo, Ernest Nadal, Sonia Macia, Carme Plasencia. First in human phase 1 dose escalation and expansion clinical trial to evaluate the safety, pharmacokinetics and antitumor activity of intravenous AROG4-01 in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT120.
Abstract CT091: Interim results from a phase 2 trial testing the safety and efficacy of VT-1953 topical gel in patients with malodorous malignant fungating wound
Authors: Arshit Narang, Prashant Prakash Lad, Shiladitya Sengupta
Journal: Cancer Research (2025)

Abstract Background: Malignant fungating wound (MFW) is a chronic inflammatory condition that afflicts 5-14% of patients with advanced cancers. MFW is extremely distressing to patients (pts) given their high burden of symptoms, including extreme malodor and pain. The malodor associated with MFWs has a significant negative effect on quality of life (QOL). Currently, there are no approved treatments for the symptoms of malodorous MFW. There is a need for an effective treatment of symptoms of MFW. Methods: VT1953 is a dual DNA gyrase and MD2-TLR inhibitor. We tested the safety and efficacy of VT-1953 2% topical gel in an ongoing open-label, investigator-initiated phase 2 clinical trial (CTRI/2024/05/066875). Male or female pts aged ≥9 with a diagnosis of malodorous MFW corresponding to 0,1 and 2 on the 6-point TELER odor scale, ECOG performance status of ≤3 and anticipated survival of ≥3 months were eligible. VT-1953 (7.5g) was applied twice daily to wounds for 14 days. The primary endpoint was the difference in the mean score of malodor associated with MFW (by investigators) using the TELER Scale on Day 14 compared to baseline (BL). Exploratory endpoints included the differences in the mean score of pain associated with MFW (by pts) using a 10-point Visual Analog Scale (VAS) on days 7 and 14 compared to BL and the mean score of QOL associated with MFW (by pts) using 5-point VAS on days 7 and 14 compared to BL. Results: At the time of this interim analysis, 8 patients were eligible and included. The results are summarized in the Table. There were no treatment-emergent side effects and no severe local skin reactions. Conclusions: Our data indicates that VT-1953 has a favorable safety profile, significantly decreased malodor and pain, and improved the QOL of pts with MFW. These results support VT-1953 as a promising option for the symptomatic management of MFW. Citation Format: Arshit Narang, Prashant Prakash Lad, Shiladitya Sengupta. Interim results from a phase 2 trial testing the safety and efficacy of VT-1953 topical gel in patients with malodorous malignant fungating wound [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT091.
Abstract CT114: FAST TIL: A more effective cell therapy product with great potential for the treatment of solid tumors
Authors: Di Wu, Ning Li, Yu Jiang, Yongjie Wang, Xinhua Zhang, Yi Zhao
Journal: Cancer Research (2025)

Abstract Adoptive cell therapy based on tumor-infiltrating lymphocytes (TIL-ACT) has achieved good clinical data in the treatment of solid tumors and has become a very promising treatment method for pan-solid tumors. It is extremely difficult to obtain tissue samples through surgery for patients with advanced tumors, and the disease progresses rapidly, which seriously restricts the development and commercial promotion of TIL drugs. Sino-cell Biomed's independently developed highly efficient, fully enclosed and automated FAST-TIL amplification platform, PowerTexp®, can significantly reduce the amount of tumor tissue required for TIL culture and shorten the in vitro expansion time. As of January 2025, the PowerTexp® platform has successfully completed TIL preparations for non-small cell lung cancer, breast cancer, melanoma, gastrointestinal cancers, head and neck tumors, gynecological tumors, soft tissue sarcomas, etc. The starting amount of tumor tissue required is &amp;lt;0.05g, the expansion success rate is &amp;gt; 95%, the total numbers of harvested cells reach 5×109 - 1×1011, and the cell viability is &amp;gt; 85%. The entire production time only takes 14 days. HS-IT101 is the first TIL product developed based on the PowerTexp® platform and is developed for pan-solid tumors. HS-IT101 has excellent quality characteristics, with the proportion of CD3+ cells &amp;gt; 80% and the proportion of stem cells (CD39-CD69-) &amp;gt; 20%. Currently, the phase I clinical trial has started for HS-IT101 (NCT06342336) since Jan 2024. Citation Format: Di Wu, Ning Li, Yu Jiang, Yongjie Wang, Xinhua Zhang, Yi Zhao. FAST TIL: A more effective cell therapy product with great potential for the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT114.
Abstract CT139: A phase I study of HG146: A novel selective HDAC inhibitor, as single-agent in patients with advanced solid tumors and lymphomas
Authors: Xiaodong Huang
Journal: Cancer Research (2025)

Abstract Background: Histone Deacetylase (HDAC) is a well-defined target family for cancer therapy. HG146 is an HDAC-1/IIb subtype-specific HDAC inhibitor. Compared with other marketed HDAC inhibitors, HG146 shows superior in vitro activity, resulting in potent proliferation inhibition across a wide range of both hematological as well as solid cancer cell lines. Mechanically, we found that HG146 elicited a robust suppression of c-MYC transcription. Consistent with its potent in vitro activity, HG146 significantly inhibited the growth of xenograft tumors derived from various hematological as well as solid tumor models in vivo. Method: The phase I study (NCT04977167) of HG146 utilized an accelerated dose escalation for the initial dose levels followed by a 3+3 design to determine the recommended phase 2 dose (RP2D). Safety profile and preliminary anti-tumor activity of HG146 in patients with advanced solid tumors and lymphomas were evaluated. Results: A total of 27 patients enrolled the trial and 24 patients (3 with multiple myeloma, 16 with solid tumors, and 5 with lymphomas) were evaluable for responses. Among them, 1 achieved partial response (PR), 17 had stable disease (SD), and 6 had progressive disease (PD). The longest progression-free survival from one patient with adenoid cystic carcinoma (ACC) reached 21 months and this patient is still receiving treatment. Moreover, HG146 demonstrated a good safety profile, with mostly grade 1-2 adverse events. Based on the Phase I study results, recurrent/metastatic ACC was selected for the Phase II clinical trial. Citation Format: Xiaodong Huang. A phase I study of HG146: A novel selective HDAC inhibitor, as single-agent in patients with advanced solid tumors and lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT139.
Abstract CT173: Neoadjuvant durvalumab and olaparib in resectable urothelial bladder cancer- Impact on its molecular profile and efficacy: Neodurvarib trial
Authors: Juan F. Rodriguez Moreno, Guillermo de Velasco, Carlos Alvarez, Ricardo Collado, Ricardo Fernandez, Sergio Vazquez, Juan Antonio Virizuela, Pablo Gajate, Albert Font, Nuria Lainez, Elena Sevillano, Osvaldo Grana Castro, Luis Beltran, Rodrigo Madurga, Cristina Rodriguez-Antona, Pedro Berraondo, Sergio Ruiz-Llorente, Jesus Garcia-Donas
Journal: Cancer Research (2025)

Abstract BACKGROUND: PARP inhibition by olaparib and immune system activation due to PD-L1 binding with durvalumab have been suggested as synergistic strategies. Thus, a comprehensive molecular characterization of tumors treated with this combination could support its rational development. Neoadjuvant bladder cancer could serve as an ideal setting for this purpose. METHODS: We designed a phase II trial with durvalumab plus olaparib to analyze the dynamics of biomarkers in both pre- and post-treatment settings. Twenty-nine patients were enrolled. Genomic and transcriptomic profiles, as well as immune cell populations, were assessed at baseline and cystectomy. RESULTS: The combination was well tolerated, with 26 (90%) patients undergoing cystectomy. Among the 29 patients treated, a pathological complete response was observed in 13 cases (44.8%). Mutational patterns, tumor mutation burden, and homologous recombination deficiency did not vary throughout treatment and did not correlate with outcomes. However, a shift towards stromal phenotypes and an overexpression of epithelial-mesenchymal transition signature were observed after therapy and in resistant tumors. Additionally, an increase in circulating CD4+ CD27- CD28- T cells was observed in responders. CONCLUSION: Neoadjuvant durvalumab plus olaparib appears to be active in bladder cancer. Transcriptional adaptations, rather than new mutations, could be a key mechanism of resistance. Citation Format: Juan F. Rodriguez Moreno, Guillermo de Velasco, Carlos Alvarez, Ricardo Collado, Ricardo Fernandez, Sergio Vazquez, Juan Antonio Virizuela, Pablo Gajate, Albert Font, Nuria Lainez, Elena Sevillano, Osvaldo Grana Castro, Luis Beltran, Rodrigo Madurga, Cristina Rodriguez-Antona, Pedro Berraondo, Sergio Ruiz-Llorente, Jesus Garcia-Donas. Neoadjuvant durvalumab and olaparib in resectable urothelial bladder cancer- Impact on its molecular profile and efficacy: Neodurvarib trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT173.
Abstract CT068: A phase 1/2, open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics, and anti-tumor activity of YH32367 in patients (pts) with HER2+ locally advanced/metastatic (a/m) solid tumors
Authors: Do-Youn Oh, SunYoung Rha, Jin Seok Ahn, Ganessan Kichenadasse, Jennifer Man, Yukyung Kim, Mikyung Kim, NaMi Lee, Yeji Lim, Jiah Kang, Mi-Jung Kwon, Eunjung Lee, Young Bong Park, Minji Choi, Sung-Bae Kim
Journal: Cancer Research (2025)

Abstract Background: YH32367, a HER2 x 4-1BB bispecific antibody engineered to amplify tumor-localized super-agonist activity of 4-1BB while minimizing off-target toxicity, showed potent preclinical anti-tumor and long-term immune memory effects. We report dose escalation results of a 2-part Phase 1/2 study. Methods: Pts with HER2+ (IHC3+ or IHC2+/ISH+) locally a/m solid tumors refractory/intolerant to standard therapy received intravenous YH32367 on Day 1 of 21-day cycles across 8 dose levels (0.3-30 mg/kg). Primary endpoint was treatment emergent adverse events (TEAEs) up to Day 21; secondary endpoints included pharmacokinetics (PK), objective response rate (ORR), disease control rate (DCR), and duration of response (DoR). Results: At data cutoff (May 24, 2024), 32 pts enrolled across 8 dose levels (63% male; median age, 60 yrs; most common tumors, biliary tract [BTC; n=14 {44%}] and gastric [n=9 {28%}]; median [range] prior treatment lines, 2 [0-7]; prior trastuzumab-based regimen, 1 [0-3]). No dose-limiting toxicities were observed; maximum-tolerated dose was not reached. Overall, 10/32 (31%) pts had treatment-related AEs (TRAEs; 1 [3%] grade ≥3; Table), most commonly pyrexia (5 [16%]) and chills (4 [13%]); 1 TRAE led to death (0.75 mg/kg). PK exposure increased slightly greater than dose-proportionally, attributable to target-mediated drug disposition. Serum s4-1BB levels showed a dose-dependent increase after YH32367 administration. Confirmed partial response was achieved in 7/31 pts overall (ORR, 23%; DCR, 55%; median [95% CI] DoR, not reached [NR; 4.2-NR]; Table), and in 4/13 pts with BTC (ORR, 31%; DCR, 62%; DoR, NR [8.3-NR]). Conclusions: YH32367, at doses ≤30 mg/kg, showed favorable safety, promising clinical benefit, and non-linear PK in previously treated pts with HER2+ a/m solid tumors, supporting further development in the dose optimization phase. Citation Format: Do-Youn Oh, SunYoung Rha, Jin Seok Ahn, Ganessan Kichenadasse, Jennifer Man, Yukyung Kim, Mikyung Kim, NaMi Lee, Yeji Lim, Jiah Kang, Mi-Jung Kwon, Eunjung Lee, Young Bong Park, Minji Choi, Sung-Bae Kim. A phase 1/2, open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics, and anti-tumor activity of YH32367 in patients (pts) with HER2+ locally advanced/metastatic (a/m) solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT068.
Abstract CT116: A first-in-human phase 1 study on the safety, PK, receptor occupancy, and pharmacodynamic markers of SPX-303, a first-in-class LILRB2×PD-L1 bispecific antibody
Authors: Justin Moser, Hao Xie, Yujie Zhao, Yousef Zakharia, Dongdong Li, Brandon William, Dinh-Duc Nguyen, Jack Hovey, Tiffany Li, Robert Cai, Jichun Ma, Jingdong Qin, Martin Siekierzycki, Anthony Haight, Hua Jin, Weiwei Mao, Kevin Bin Li, Gui-Dong Zhu
Journal: Cancer Research (2025)

Abstract Background: Leukocyte immunoglobulin-like receptor B2 (LILRB2) suppresses immune cell activation, particularly within myeloid cells in the tumor microenvironment (TME), while the PD-1/PD-L1 axis serves as a key immune checkpoint that inhibits T-cell function. SPX-303 is a novel bispecific antibody designed to simultaneously block LILRB2 and PD-L1, thereby revitalizing antitumor immune responses. Here, we present initial findings from the ongoing first-in-human Phase 1 trial of SPX-303 in patients with advanced solid tumors, including safety, pharmacokinetics (PK), and receptor occupancy (RO). Methods: This is an open-label, multicenter Phase 1 study for patients with advanced solid malignancies with 3+3 dose-escalation design, followed by an expansion cohort at the recommended Phase 2 dose (RP2D). SPX-303 is administered intravenously every three weeks and safety is assessed through CTCAE v5.0 criteria. Primary Objectives of this study are to determine the safety, tolerability, and RP2D of SPX-303. Secondary endpoints include antitumor activity as well as characterization of the PK and PD of SPX-303. This study is currently open and enrolling in escalation cohorts. Citation Format: Justin Moser, Hao Xie, Yujie Zhao, Yousef Zakharia, Dongdong Li, Brandon William, Dinh-Duc Nguyen, Jack Hovey, Tiffany Li, Robert Cai, Jichun Ma, Jingdong Qin, Martin Siekierzycki, Anthony Haight, Hua Jin, Weiwei Mao, Kevin Bin Li, Gui-Dong Zhu. A first-in-human phase 1 study on the safety, PK, receptor occupancy, and pharmacodynamic markers of SPX-303, a first-in-class LILRB2×PD-L1 bispecific antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT116.
Abstract CT085: A multi-cohort study of treatment regimens for metastatic colorectal cancer (mCRC): Subgroup analysis of sequential therapy between fruquintinib and regorafenib
Authors: Wangxia Lv, Bixia Liu, Tingting Feng, Zhong Shi, Junchi Cheng, Haijun Zhong, Meiqin Yuan
Journal: Cancer Research (2025)

Abstract Background: In the management of mCRC, the selection of optimal treatment regimens, particularly when considering sequential therapies, is crucial for improving patient outcomes. Fruquintinib (Fru) is a small-molecule tyrosine kinase inhibitor (TKI) that targets VEGFR-1/2/3 to inhibit the proliferation of vascular and lymphatic endothelial cells, thereby exerting its effects in suppressing tumor growth and metastasis. Regorafenib (Reg) exerts inhibitory effects on multiple targets including VEGFR-1/2/3, TIE-2, and CSF-1R. However, the optimal sequencing of these agents remains unclear. This study aims to compare the effectiveness of different sequential treatment approaches involving Fru and Reg. Methods: This study included mCRC patients (pts) who received sequential treatment regimens including both Fru and Reg. Pts were divided into two groups based on their treatment sequence: the Fru-Reg group (treated with Fru followed by Reg) and the Reg-Fru group (treated with Reg followed by Fru). In addition, a subgroup analysis was conducted based on the treatment regimen received before the sequential therapy, including monotherapy (mono) or combination therapy. The primary endpoint was median overall survival (mOS), and statistical analysis was performed by comparing the hazard ratio (HR) and P-value among the groups. Results: A total of 53 pts were included, with 35 pts in the Fru-Reg group and 18 pts in the Reg-Fru group. In the mono subgroup, there were 19 pts in the Fru-Reg (mono) group and 7 pts in the Reg-Fru (mono) group. In the total pts population, the mOS for the Fru-Reg (Total) group was 21.17 months compared to 19.12 months for the Reg-Fru (Total) group. Within the mono subgroup, the mOS for the Fru-Reg (mono) group was 19.05 months versus 15.79 months for the Reg-Fru (mono) group. Conclusion: This study provides valuable insights into the comparative effectiveness of sequential Fru and Reg treatment regimens in pts with mCRC. The results showed that in the overall patient population and mono subgroup, pts with Fru sequential Reg had a trend of benefit in mOS compared with pts with Reg sequential Fru opposite, but the difference was not statistically significant, we will continue to increase the sample size of the enrolled pts to further validate this finding. Citation Format: Wangxia Lv, Bixia Liu, Tingting Feng, Zhong Shi, Junchi Cheng, Haijun Zhong, Meiqin Yuan. A multi-cohort study of treatment regimens for metastatic colorectal cancer (mCRC): Subgroup analysis of sequential therapy between fruquintinib and regorafenib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT085.