tbuckley/cabot-search huggingface dataset:
CD8 radiomics signature to assess inter-lesion spatial heterogeneity and cold liver lesions in advanced non-small cell lung cancers treated with durvalumab.
Authors: Roger Sun, Yanis Emeriau, Samir Achkar, Diana Mitrea, Adrien Laville, Nicolas Deny, Sophie Bockel, Ines Chaffai, Linda Mrissa, Vjona Cifliku, Fereshteh Talebi, Wenxia Wu, Cecile Le Pechoux, Fabrice Barlesi, Charlotte Robert, Antonin Levy, Eric Deutsch
Journal: Journal of Clinical Oncology (2024)

2511 Background: The objective of this study was to assess whether a validated CD8 radiomics signature may help to evaluate patient inter-lesion heterogeneity and to predict the clinical outcome of advanced non-small cell lung cancers (NSCLC) patients treated with durvalumab in Study 1108 phase I/II trial (NCT01693562). Methods: Clinical data and imaging data from patients with naïve and pretreated advanced NSCLC who received durvalumab monotherapy were used. Radiomic features were extracted on contrast-enhanced CT scans and a validated CD8 radiomics signature was applied. A progressive lesion was defined by an increase in lesion longest diameter of 20% at 8 weeks. Dispersion metrics of the radiomics signature were estimated to evaluate the impact of inter-lesion heterogeneity on patient’s response. Results: A total of 188 patients were included in this study, accounting for a total of 1137 lesions (median [IQR] = 4 [3 - 9] lesions per patient) evaluated at baseline using a radiomics approach. A low CD8 radiomics score at baseline was associated with a significantly higher risk of progression at the lesion-level (AUC=0.59, P-value&lt;0.0001), and was especially performant for liver lesions (AUC=0.66, P-value=0.0002). At the patient level, the least infiltrated lesion of a patient according to the radiomics score of CD8 T-cells was positively associated with OS (HR=0.70, P-value=0.029) and PFS (HR=0.68, P-value=0.014), the highest values being associated with the best outcomes. 55 patients had liver lesions, with worse prognosis than patients without liver lesion (HR=2 for OS and PFS, P-value = 0.00012 and 0.00022 respectively). In these patients, the CD8 radiomic score enabled the stratification of patients according to hot and cold liver metastasis (HR=0.6, P-value=0.072 and HR=0.54, P-value=0.038 for OS and PFS respectively). A 4-class stratification of the whole cohort based on the least infiltrated (cold/hot) and liver or non-liver lesion was independently associated with clinical outcomes. These radiomics approaches have shown independent prognostic values when adjusting for PD-L1 status in multivariate analyses (Table). Conclusions: These results confirm the predictive value at a lesion level and the patient level of the biologically inspired CD8 radiomics score for advanced NSCLC patients treated with durvalumab. It has shown interesting results in discriminating outcomes of patients with liver lesions by identifying hot and cold lesions. [Table: see text]
Safety and preliminary efficacy of EIK1001 in combination with pembrolizumab in participants with advanced solid tumors.
Authors: Anthony W. Tolcher, Drew W. Rasco, Melissa Lynne Johnson, Manish R. Patel, Angela Tatiana Alistar, Julia Wanda Cohen, Carolyn Cho, Meihua Wang, Etah Kurland
Journal: Journal of Clinical Oncology (2024)

2521 Background: Immune checkpoint inhibitors (ICIs) relieve immunosuppression of tumor-reactive T cells and enhance antitumor immune response; however, not all patients benefit and some become refractory. EIK1001 is a Toll-like receptor (TLR)7/8 agonist that stimulates myeloid and plasmacytoid dendritic cells, activating immune and inflammatory responses. This dual activity provides another pathway, distinct from effects on checkpoint proteins, to enhance antitumor T-cell activity alone or in combination with ICIs. Methods: Study BDB001-101 was a Phase 1, open-label, dose-escalation/expansion study of EIK1001 as either monotherapy (mono Rx; previously reported) or combined with pembrolizumab (comb Rx). Enrollment criteria included participants (pts) ≥ age 18 with confirmed, RECIST-measurable advanced solid tumors. Primary study objectives included safety and tolerability, and secondary objectives included evaluation of dose-limiting toxicities, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy by RECIST 1.1. During comb Rx dose escalation, pts received a range of doses of EIK1001 (QW IV) in combination with pembrolizumab (200 mg Q3W). Results: Fifty-one pts (median age 67 [range 33 to 86]) with multiple, distinct histological tumor types and with a median of 3 prior Rx regimens were enrolled. Overall, a total of 42/51 (82.4%) comb Rx pts experienced a treatment-related adverse event (TRAE). A total of 9/51 (17.7%) experienced a ≥ Grade 3 TRAE, including fatigue, cytokine release syndrome (CRS), hemiparesis, hypertension, joint range of motion reduced, muscular weakness, pancreatitis, rash (maculopapular), skin plaque, and stomatitis. Overall, 5/51 (9.8%) experienced manageable CRS, with only 1 discontinuation due to CRS. There were no deaths due to TRAEs. Of the efficacy-evaluable pts (n = 50), complete response (CR) or partial response (PR) was observed for 7/50 (14.0%), including 3 CR and 4 PR. Disease control (including CR, PR, or stable disease) was observed in 24/50 (48.0%). The median duration of response was 10 months (range = 4 to 32 months). Responses were observed in pts with prior anti-PD-1 exposure as well as in those with low or negative PD-L1 tumor expression. EIK1001 PK was linear and dose-proportional, and combination with pembrolizumab did not affect EIK1001 PK. Conclusions: Overall, EIK1001 was well-tolerated with a manageable safety profile and showed encouraging preliminary efficacy across several tumor types in combination with pembrolizumab. Responses were observed even in heavily pretreated patients not anticipated to respond to pembrolizumab monotherapy. Further development of EIK1001 is underway. Clinical trial information: NCT03486301 .
High-dimensional longitudinal immune profiling uncovers a dual role of the CXCL9/CXCR3, CXCL13/CXCR5, and CCL11/CCL3 axis in the coupling of immune-related adverse events to immune checkpoint inhibitor response.
Authors: Michel Obeid, Victor Joo, Douglas Daoudlarian, Robin Bartolini, Hasna Bouchaab, Sofiya Latifyan, Nuria Mederos, Karim Abdelhamid, Valérie Mosimann, Nabila Ferahta, Keyvan Shabafrouz, Giuseppe Pantaleo, Solange Peters
Journal: Journal of Clinical Oncology (2024)

2512 Background: Additional characterization is required to understand the immune network signatures and immunophenotypes that link immune-related adverse events (irAEs) to immune checkpoint inhibitor (ICI) therapy responses in cancer patients. Methods: A comprehensive immune profiling analysis was conducted on whole blood and peripheral blood mononuclear cells (PBMC) from 165 oncology patients with various irAEs, including colitis (n=64), myocarditis (n=19), pneumonitis (n=25), arthritis (n=24), and cytokine release syndrome CRS (n=33), and compared to a cohort of 219 cancer patients prior to ICI treatment. Results: Following ICI therapy on cycle 2 day 1 (C2D1), we observed significant increases in IL-6, CCL2, CXCL9, CXCL10, and CXCL13 levels preceding irAEs. CXCL9 was specifically upregulated during the development of colitis, arthritis, CRS, and myocarditis, while CXCL13 increased only in CRS, and CCL3 only in myocarditis and CRS, with no CCL11 upregulation in any irAE. High levels of CXCL9, high CCL11 and low CXCL13 strongly correlated with improved oncologic outcomes in different irAEs. Compared to other cluster, in the high CXCL9 cluster, 5-year overall survival (OS) was significantly improved (HR = 10.26 [95% CI, 1.27-82.82], p = 0.029) in colitis (n=20), in CRS (n=21) (HR = 6.45 [95% CI, 1.60-25.99], p = 0.009), and in arthritis. In the high CCL11 cluster, 5-year OS was significantly improved in pneumonitis (n=15), (HR = 4.04 [95% CI, 1.05-15.46]). Conversely, in myocarditis, the high CXCL13 cluster (n=9) was associated with decreased 2-year OS (HR = 6.05 [95% CI, 1.03-35.48], p = 0.046). It is important to note that the CXCL9-driven immunophenotypes were characterized by low IL-6. Notable observations include CD38 upregulation and large-scale activation of CD8 memory subsets during ICI therapy, concomitant with increased circulation of immature neutrophils at the onset of irAEs diagnosis. This event may increase the migration of TCRγδ, NK, DC, and CD8 cells to tumor sites through CXCR3/CXCL9 interactions. Conclusions: This study unravels intricate connections between immune activation and tumor response. CXCL9, CCL11, and CXCL13 emerge as pivotal biomarkers bridging the gap between ICI therapy effectiveness and distinct irAEs-associated immunophenotypes.
Results from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma.
Authors: Susanna Varkey Ulahannan, Thomas Urban Marron, Haeseong Park, John M. Kaczmar, Ryan D. Stephenson, Nehal J. Lakhani, Greg Andrew Durm, Jaspreet Singh Grewal, Anthony B. El-Khoueiry, Jason J. Luke, Courtney Beers, Swaminathan Murugappan, Patricia LoRusso, Douglas Adkins, J. Randolph Hecht
Journal: Journal of Clinical Oncology (2024)

2524 Background: TTX-080 is an IgG1 monoclonal antibody targeting HLA-G. This Ph1a/1b study evaluated the safety and preliminary efficacy of TTX-080 alone or in combination with cetuximab (Cetx) or pembrolizumab (Pem) in multiple solid tumor cohorts (NCT04485013). Herein, we report the safety from the Ph1a and preliminary efficacy data from Ph1b cohorts evaluating TTX-080 + Cetx in pts with head and neck squamous cell carcinoma (HNSCC) and WT RAS/BRAF, HER2-Neg metastatic colorectal cancer (mCRC) tumors. Methods: In Ph1a, pts with advanced solid tumors received single agent TTX-080 at escalating doses in a 3+3 design from 0.2-20 mg/kg IV Q3W. In the mCRC and HNSCC arms of Ph1b, pts were treated with RP2D of TTX-080 + Cetx. Patients were followed for safety and anti-tumor activity. Biopsies and blood samples were collected for biomarker analyses. Results: As of 08-Dec-23, 202 pts have received TTX-080 alone or in combination (40 pts in Ph1a and 162 pts in Ph1b). In Ph1a TTX-080 monotherapy dose-escalation, MTD was not reached and no DLT was reported. TTX-080 treatment-related AE (TRAE) of arthralgia, fatigue, and decreased appetite were seen in at least 5% of pts. R2PD for TTX-080 was determined to be 20 mg/kg IV Q3W. In Ph1b of TTX-080 alone or in combination (Cetx or Pem), the most common TRAEs in at least 5% of subjects were fatigue, nausea, anemia, diarrhea, AST increase, headache, vomiting and pruritis. Preliminary efficacy data from the select Ph1b TTX-080 + Cetx subset of pts are shown in Table. Significant HLA-G related immune cell changes in the peripheral blood and in tumors will be presented. Conclusions: TTX-080 is well tolerated alone and in combination with Cetx. TTX-080 + Cetx demonstrates promising activity in pts with HPV-Neg HNSCC and WT RAS/BRAF/Her2-Neg mCRC as manifested by the responses and PFS. These early findings warrant further investigation of TTX-080 + Cetx in a randomized controlled study against standard of care in mCRC and HNSCC. Clinical trial information: NCT04485013 . [Table: see text]
Phase I study of GUCY2C CAR-T therapy IM96 in patients with metastatic colorectal cancer.
Authors: Changsong QI, Chang Liu, Jian Li, Jifang Gong, Xicheng Wang, Zhenghang Wang, Xin-an Lu, Ting He, Yanping Ding, Fei Wu, Dongqun Liu, Lin Shen
Journal: Journal of Clinical Oncology (2024)

2518 Background: The clinical outcomes of metastatic colorectal cancer (mCRC) therapies are limited, especially for liver metastasis. Guanylyl cyclase 2C (GUCY2C) is ectopically expressed in all stages of CRC and intestinally restricted. GUCY2C-targeted CAR-T (IM96) was developed and phase I study was conducted to evaluate the safety and efficacy (NCT05287165). Methods: In this open-label, 3+3 dose-escalation study, IM96 was evaluated in GUCY2C-positive mCRC patients (pts) failed to ≥3 lines of therapies. Pts were pre-treated with fludarabine and cyclophosphamide, and received a single infusion of IM96 at the dose of 3×10 8 (DL1), 6×10 8 (DL2), 12×10 8 (DL3), or 20×10 8 (DL4) CAR-T cells. Dose-expansion study was performed at DL3. The primary objectives were safety and toxicity, and the secondary objectives were efficacy and pharmacokinetic profile. Results: As of December 2023, 20 pts were enrolled and infused with IM96. The follow-up time was 7-19 months for all pts. The median age was 52.5, and 11/20 cases were male. Liver metastasis was found in 11/20 cases (55%), proficient mismatch repair (pMMR) in 20/20 pts (100%), KRAS mutation in 12/20 pts (60.0%), NRAS mutation in 1/20 pts (5.0%), and BRAF mutation in 3/20 pts (15.0%). Bridging therapies were used in 19 pts. Only 1/20 pt (5.0%) showed neurotoxicity and ≥grade 3 cytokine release syndromes (CRS). Grade 1-2 CRS occurred in 16/20 pts (80.0%) with dramatic increase of interleukin-6. Grade 1-3 rash was observed in 14/20 pts (70.0%). Grade 3 diarrhea occurred in 11/20 pts (55.0%), and grade 1-3 oral mucositis appeared in 7/20 pts (35.0%), only in DL2, DL3 and DL4 groups. Dose-limiting toxicity and maximum tolerated dose were not achieved. Among 19 evaluable pts, the disease control rate (DCR) was 73.7%, and the objective response rate (ORR) was 26.3%. In DL3 group, pts showed an ORR of 40.0%, nevertheless of liver metastasis or not. The median progression-free survival time was 7 months, and the median duration of response was 10 months in DL3 group. No responding pts showed disease progression within 6 months. Tumor responses were correlated with significant decreases in carcinoembryonic antigen levels among all pts. Conclusions: This study demonstrated that IM96 has durable efficacy with acceptable safety profile in pMMR mCRC pts, in particularly, showing high therapeutic potential in liver metastasis pts. Clinical trial information: NCT05287165 .
The impact of proton-pump inhibitor use on the incidence and severity of gastrointestinal toxicity to checkpoint inhibition.
Authors: Yinghong Wang, Malek Shatila, Christine Catinis, Samanthika Devalaraju, Stephen Glombicki, Irene Jeong-AH Lee, Sean Ngo, Kei Takigawa, Linfeng Lu, Nitish Mittal, Elliot Baerman, Abdullah Sagar Aleem, Antonio Pizuorno Machado, Anusha Thomas
Journal: Journal of Clinical Oncology (2024)

2657 Background: Checkpoint inhibitors (ICIs) for cancer come with the risk of immune-related adverse events (irAE). Upper and lower gastrointestinal (UGI and LGI, respectively) tract inflammation are common toxicities. Proton pump inhibitors (PPIs) are frequently used to treat immune-mediated UGI irAEs. Studies have suggested that these agents may worsen LGI irAEs. Our study aims to observe the effect of PPI use on the incidence and severity of GI irAEs. Methods: This was a single-center retrospective chart review including all patients who received ICIs. Patients were categorized based on PPI usage and screened for upper or lower GI toxicities. PPI use was counted if the medication was received at least three months before starting ICI and one year after the last ICI dose. Results: 16,849 patients were included. 2,114 (12.5%) patients received PPIs (PPI group – PG), while 14,735 (87.5%) did not (non-PPI group - NPG). 46 (2.2%) PG patients developed UGI irAE compared to 43 (0.3%) in the NPG (p&lt;0.001), with no difference in severity or need for immunosuppression (p&gt;0.05). PG patients were more likely to be hospitalized however (p=0.021). 115 (5.4%) PG patients developed an LGI irAE compared to 173 (1.2%) in the nPG (p&lt;0.001). 80.7% of the PG presented with ≥grade 2 diarrhea and 52.0% with ≥grade 2 colitis, compared to 69.1% and 38.5% of the NPG, respectively (p&lt;0.05). PG patients more frequently needed steroid treatment (60.0% vs. 42.2% in the NPG, p=0.004) and SIT (41.7% vs. 24.9%, p=0.003), and were less likely to have symptom resolution (78.5% in the PG vs. 89.6% in the NPG, p=0.020). A dose-dependent effect was observed. Every 10mg increase in PPI dose led to more frequent hospitalization for UGI irAEs (OR: 1.6, p=0.049) and more reliance on steroids (OR:1.3, p=0.044) and SIT (OR: 1.3, p=0.037) for LGI irAEs. This was also associated with less hospitalization and recurrence rates for LGI irAEs (p&lt;0.05). Conclusions: Our study shows that PPI use during immunotherapy may increase the risk of developing a GI irAE. PPI use does not seem to impact the severity of upper GI irAEs aside from a higher hospitalization rate. However, PPI use may lead to a more severe disease course for lower GI toxicities. Prospective studies are needed to validate these results. [Table: see text]
Publisher Correction: APOE4 homozygosity represents a distinct genetic form of Alzheimer’s disease
Authors: Juan Fortea, Jordi Pegueroles, Daniel Alcolea, Olivia Belbin, Oriol Dols-Icardo, Lídia Vaqué-Alcázar, Laura Videla, Juan Domingo Gispert, Marc Suárez-Calvet, Sterling C. Johnson, Reisa Sperling, Alexandre Bejanin, Alberto Lleó, Víctor Montal
Journal: Nature Medicine (2024)
First-in-human study of ZGGS18, a dual specific antibody targeting VEGF and TGF-β, as monotherapy in patients with advanced solid tumors.
Authors: Chuan Hua Zhao, Jianhua Shi, Xiaoli Chai, Lirong Tan, Lihua Wu, Li Zheng, Dan Cao, Gang Mai, Lianlian Fan, Yanjun Mi, Jufeng Wang, Xinghua Han, Jianming Xu
Journal: Journal of Clinical Oncology (2024)

2523 Background: ZGGS18 is a bifunctional antibody fusion protein, which consists of a monoclonal antibody (optimized Bevacizumab) against vascular endothelial growth factor A (VEGF-A) and an engineered human transforming growth factor-β receptor II extracellular domain (TGF-β RII ECD). It can specifically bind VEGF-A and "capture" TGF- β isomers. It plays a synergistic role in inhibiting tumor growth, such as inhibiting tumor angiogenesis and reducing tumor metastasis. In addition, ZGGS18 can also improve and regulate the tumor microenvironment, so it can enhance the tumor-killing effect in combination with anti-PD-(L) 1 antibody and other tumor immunotherapeutic drugs. We conducted a Phase 1 clinical study to assess the tolerability and safety of this drug. Methods: It was a dose-escalation study. Subjects were patients with advanced solid tumors who failed to the available standard treatments. The dose groups were set from 0.3 to 20 (0.3, 1, 3, 6, 10, 15, 20) mg/kg, intravenous infusion, once every 2 weeks. An accelerated titration design (ATD) was utilized in the first three dose groups and a standard "3+3" design was used in the rest doses. The first 28-day period was defined as the dose-limiting toxicity (DLT) observation period. Subjects could continue to receive ZGGS18 until treatment discontinuation criteria were met. Tumor response was assessed by RECIST1.1. Results: At the data cut-off (4 Jan 2024), 21 patients (14 males and 7 females) were enrolled, with a median age of 60 years. 13 (61.9%) of them received at least 2 lines of antineoplastic therapies. 76.2% (16/21) of patients experienced treatment-related adverse events (TRAEs) and 19.0% (4/21) of patients had grade 3 TRAEs (1 Lower gastrointestinal hemorrhage in the 10 mg/kg, 1 pneumonia in the 15 mg/kg, 1 anemia in the 20 mg/kg, and 1 blood fibrinogen decreased in the 20 mg/kg dose group). Wherein, the grade 3 blood fibrinogen decreased was a DLT event. The most frequent TEAEs (with incidence &gt;10%) were anemia, lymphocyte count decreased, gingival bleeding, epistaxis, hypoalbuminemia, proteinuria, hypocalcemia, hypokalemia, fever, aspartate aminotransferase increased, bile acids increased, and disease progression. There is one subject with endometrial carcinoma who has received 19 infusions of ZGGS18 and is remaining in this study, and another subject with rectal carcinoma had 29.65% tumor shrinkage at week 12. The C max and AUC increased from 0.3-20 mg/kg approximately in dose proportion. Conclusions: ZGGS18 demonstrated its safety and tolerability in this dose-escalation study, along with a good PK profile, providing a good basis for monotherapy and/or combination therapy for future use. Clinical trial information: NCT05584800 .
Author Correction: Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease
Authors: Anubha Agarwal, Priya M. Mehta, Tyler Jacobson, Nilay S. Shah, Jiancheng Ye, JingJing Zhu, Q. Eileen Wafford, Ehete Bahiru, Angharad N. de Cates, Shah Ebrahim, Dorairaj Prabhakaran, Anthony Rodgers, Mark D. Huffman
Journal: Nature Medicine (2024)

In the version of the article initially published, the sentence "The scientific foundation underlying the concept of a fixed-dose combination, or polypill, therapy targeting multiple modifiable ASCVD risk factors was first proposed in patents GB 0100548.7 and GB 008791.
Safety and preliminary efficacy results of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: A phase 1 dose escalation and expansion study.
Authors: Li Zheng, Dai Ruihong, Ying Jieer, Qi Xu, Zengqing Guo, Changlu Hu, Yuping Sun, Zuoxing Niu, Jihui Hao, Mingjun Zhang, Dai Guanghai, Dong Hua, Yueyin Pan, Xin Wang, Shuqing Wei, Xiaobing Chen, Xinhe Yu, Yulong Zhang, Hui Zhou, Feng Bi
Journal: Journal of Clinical Oncology (2024)

2519 Background: CLDN18.2 expression has been observed in various solid tumors especially in gastric cancer, indicating its potential as a novel target for anti-tumor therapy. IBI389 is an anti-CLDN18.2/CD3 bispecific antibody that induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the membrane of tumor cells. Herein, we report preliminary results from a phase I study to evaluate safety and efficacy of IBI389 in patients (pts) with advanced solid tumors. Methods: Eligible pts with advanced solid tumors who failed or were intolerant to standard treatments were enrolled. The dose escalation of IBI389 monotherapy used intra-patient dose escalation with accelerated titration and the classic 3+3 design (0.003 µg/kg to 600 µg/kg). Selected dose levels were expanded in pts with advanced gastric/gastroesophageal junction cancer (G/GEJ C) and pancreatic ductal adenocarcinoma (PDAC). The primary objective was safety. Secondary objective was efficacy assessed by investigator per RECIST v1.1 including objective response rate (ORR) and disease control rate (DCR). Results: As of January 9, 2024, a total of 114 pts were enrolled (males: 67.5%, median age: 60.0 years, G/GEJ C: 32.5%, PDAC: 57.9%, stage IV: 81.6%). No dose-limiting toxicity (DLT) was observed during dose escalation. The MTD was not reached. In all pts, treatment-emergent adverse events (TEAEs) occurred in 112 (98.2%) pts including 76 (66.7%) pts with grade ≥3 TEAEs. Treatment-related adverse events (TRAEs) occurred in 111 (97.4%) pts including 63 (55.3%) pts with grade ≥3 TRAEs. The most common grade ≥3 TRAEs (≥ 4%) were gamma-glutamyl transferase increased (21.9%), lymphocyte count decreased (13.2%) and nausea (4.4%). Cytokine release syndrome (CRS) related adverse events occurred in 65 (57.0%) pts including 1 (0.9%) pts with grade 3 CRS and no grade 4 or 5 CRS. TEAEs leading to dose interruption and treatment discontinuation occurred in 44 (38.6%) and 8 (7.0%) pts. Preliminary efficacy of IBI389 was observed in pts with CLDN18.2 expression ≥10% (immunohistochemistry 2+/3+). In G/GEJ C pts with previous treatments ≥2 lines receiving IBI389 at various dose levels ranging from 10µg/kg to 600 µg/kg (n=26), 8 pts had partial response (PR) and 11 pts had stable disease (SD). The ORR was 30.8% (95%CI: 14.3-51.8) and DCR was 73.1% (95%CI: 52.2-88.4). Conclusions: IBI389 showed manageable safety profiles in pts with advanced solid tumors and preliminary efficacy in CLDN18.2-positive pts with G/GEJ C. Clinical trial information: NCT05164458 .