bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from A Phase 1, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: September 2024

Abstract
Purpose: To evaluate DS-6157a, an antibody-drug conjugate targeting G-protein coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST). Patients and methods: In this phase 1 multicenter, open-label, multiple-dose study, patients with previously-treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy. Results: A total of 34 patients enrolled. DS-6157a was well-tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-related adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed. Conclusions: Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.
Data from Development and multicenter case-control validation of urinary comprehensive genomic profiling for urothelial carcinoma diagnosis, surveillance, and risk prediction
Authors: Salari Keyan , Sundi Debasish , Lee Jason J. , Wu Shulin , Wu Chin-Lee , DiFiore Gabrielle , Yan Q. Robert , Pienkny Andrew , Lee Chi K. , Oberlin Daniel , Barme Greg , Piser Joel , Kahn Robert , Collins Edward , Phillips Kevin G. , Caruso Vincent M. , Goudarzi Mahdi , Garcia-Ransom Monica , Lentz Peter S. , Evans-Holm Martha E. , MacBride Andrew R. , Fischer Daniel S. , Haddadzadeh Iden J. , Mazzarella Brian C. , Gray Joe W. , Koppie Theresa M. , Bicocca Vincent T. , Levin Trevor G. , Lotan Yair , Feldman Adam S.
Published: September 2024

Abstract
Purpose: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma (UC) and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. Experimental Design: This is a multicenter case-control study utilizing banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or UC surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmpTM platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting UC tumor presence, grade, and recurrence risk were compared to cytology, cystoscopy, and pathology. Results: uCGP algorithms had a validation sensitivity/specificity of 96%/90% for initial cancer diagnosis in hematuria patients and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary UC classification demonstrated an NPV of 91%. uCGP recurrence risk prediction significantly prognosticated future recurrence (hazard ratio 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable to cytology (45% vs 42%) with much higher sensitivity (79% vs 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. Conclusions: uCGP enables noninvasive, accurate UC diagnosis and risk stratification in both hematuria and UC surveillance patients.
Data from Learning Individual Survival Models from PanCancer Whole Transcriptome Data
Authors: Kumar Neeraj , Skubleny Daniel , Parkes Michael , Verma Ruchika , Davis Sacha , Kumar Luke , Aissiou Amira , Greiner Russell
Published: September 2024

Abstract
Purpose: Personalized medicine attempts to predict survival time for each patient, based on their individual tumour molecular profile. We investigate whether our survival learner in combination with a dimension reduction method can produce useful survival estimates for a variety of cancer patients. Experimental Design: This paper provides a method that learns a model for predicting the survival time for individual cancer patients from the PanCancer Atlas: given the (16335-dimensional) gene expression profiles from 10173 patients, each having one of 33 cancers, this method uses unsupervised NMF (non-negative matrix factorization) to re-express the gene expression data for each patient in terms of 100 learned NMF Factors. It then feeds these 100 Factors into the MTLR (Multi-Task Logistic Regression) learner to produce cancer-specific models for each of 20 cancers (with >50 uncensored instances); this produces “individual survival distributions” (ISDs), which provide survival probabilities at each future time for each individual patient – which provides a patient’s risk score and estimated survival time. Results: Our NMF-MTLR concordance indices outperformed the VAECox benchmark by 14.9% overall. We achieved optimal survival prediction using pan-cancer NMF in combination with cancer-specific MTLR models. We provide biological interpretation of the NMF model and clinical implications of ISDs for prognosis and therapeutic response prediction. Conclusions: NMF-MTLR provides many benefits over other models: superior model discrimination, superior calibration, meaningful survival time estimates, and accurate probabilistic estimates of survival over time for each individual patient. We advocate for the adoption of these cancer survival models in clinical and research settings.
Data from A Phase II Study of Optimized Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma
Authors: Herr Daniel J. , Wang Chang , Mendiratta-Lala Mishal , Matuszak Martha , Mayo Charles S. , Cao Yue , Parikh Neehar D. , Ten Haken Randy , Owen Dawn , Evans Joseph R. , Stanescu Teodor , Yan Michael , Dawson Laura A. , Schipper Matthew , Lawrence Theodore S. , Cuneo Kyle C.
Published: September 2024

Abstract
Purpose: We hypothesized that optimizing the utility of stereotactic body radiation therapy (SBRT) based on the individual patient’s probability for tumor control and risk of liver injury would decrease toxicity without sacrificing local control in patients with impaired liver function or tumors not amenable to thermal ablation. Methods: Patients with Child-Pugh (CP) A to B7 liver function with aggregate tumor size >3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an IRB approved phase II clinical trial to undergo SBRT with baseline and mid-treatment dose optimization using a quantitative, individualized utility-based analysis. Primary endpoints were change in CP score of ≥2 points within 6 months and local control. Protocol-treated patients were compared with patients receiving conventional SBRT at another cancer center using overlap weighting. Results: 56 patients with 80 treated tumors were analyzed with a median follow-up of 11.2 months. Two-year cumulative incidence of local progression was 6.4% (95% CI [2.4 – 13.4]). 21% of patients experienced treatment-related toxicity within 6 months, which is similar to the rate for SBRT in patients with CP A liver function. An analysis using overlap weighting revealed similar local control (HR 0.69, 95% CI [0.25-1.91], p = 0.48) and decreased toxicity (OR 0.26, 95% CI [0.07 – 0.99], p = 0.048) compared to conventional SBRT. Conclusion: Treatment of individuals with impaired liver function or tumors not amenable to thermal ablation with a treatment paradigm designed to optimize utility may decrease treatment-related toxicity while maintaining tumor control.
Data from Prognostic markers of DNA methylation and NGS sequencing in progressive glioblastoma from the EORTC-26101 trial
Authors: Kessler Tobias , Schrimpf Daniel , Doerner Laura , Hai Ling , Kaulen Leon D. , Ito Jakob , van den Bent Martin , Taphoorn Martin , Brandes Alba A. , Idbaih Ahmed , Dômont Julien , Clement Paul M. , Campone Mario , Bendszus Martin , von Deimling Andreas , Sahm Felix , Platten Michael , Wick Wolfgang , Wick Antje
Published: September 2024

Abstract
Purpose: The EORTC-26101 study was a randomized phase 2 and 3 clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allows for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma. Experimental Design: We analyzed DNA methylation array data and panel sequencing from 170 genes of 380 tumor samples of the EORTC-26101 study. These patients were comparable to the overall study cohort in regards of baseline characteristics, study treatment and survival. Results: 295/380 (78%) of patients’ samples were classified into one of the main glioblastoma groups receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There were 10 patients (2.6%) with isocitrate dehydrogenase (IDH) mutant tumors in the biomarker cohort. Patients with RTK1 and RTK2 classified tumors had lower median OS compared to mesenchymal (7.6 vs. 9.2 vs. 10.5 months). O6-methylguanine DNA-methyltransferase (MGMT) promotor methylation was prognostic for PFS and OS. Neurofibromin (NF)1 mutations were predictive of response to bevacizumab treatment. Conclusions: Thorough molecular classification is important for brain tumor clinical trial inclusion and evaluation. MGMT promoter methylation and RTK1 classifier assignment were prognostic in progressive glioblastoma. NF1 mutation may be a predictive biomarker for bevacizumab treatment.
Data from Unique spectrum of activating BRAF alterations in prostate cancer
Authors: Chehrazi-Raffle Alex , Tukachinsky Hanna , Toye Eamon , Sivakumar Smruthy , Schrock Alexa B. , Bergom Hannah E. , Ebrahimi Hedyeh , Pal Sumanta , Dorff Tanya , Agarwal Neeraj , Mahal Brandon A. , Oxnard Geoffrey R. , Hwang Justin , Antonarakis Emmanuel S.
Published: September 2024

Abstract
Purpose:Alterations in BRAF have been reported in 3-5% of prostate cancer, although further characterization is lacking. Here, we describe the nature of BRAF alterations in prostate cancer using a large cohort from commercially available tissue and liquid biopsies subjected to comprehensive genomic profiling (CGP). Experimental Design:Tissue and liquid biopsies from patients with prostate cancer were profiled using FoundationOne®CDx and FoundationOne®Liquid CDx CGP assays, respectively. Tissue biopsies from non-prostate cancer types were used for comparison (n=275,151). Genetic ancestry was predicted using a single nucleotide polymorphism-based approach. Results:Among 15,864 tissue biopsies, BRAF-activating alterations were detected in 520 cases (3.3%). The majority (463 samples, 2.9%) harbored Class II alterations, including BRAF rearrangements (243 samples, 1.5%), K601E (101 samples, 0.6%), and G469A (58 samples, 0.4%). BRAF-altered prostate cancers were enriched for CDK12 mutations (OR 1.87, 9.2% vs 5.2%, p=0.018), but depleted in TMPRSS2 fusions (OR 0.25, 11% vs 32%, p<0.0001), PTEN alterations (OR 0.47, 17% vs 31%, p<0.0001), and APC alterations (OR 0.48, 4.4% vs 8.9%, p=0.018) relative to BRAF wild-type disease. Compared to patients of European ancestry, BRAF alterations were more common in tumors from patients of African ancestry (5.1% vs. 2.9%, p<0.0001) and Asian ancestry (6.0% vs. 2.9%, p<0.001). Conclusions: Activating BRAF alterations were detected in ~3% of prostate cancers, and most were Class II mutations and rearrangements; BRAF V600 mutations were exceedingly rare. These findings suggest that BRAF activation in prostate cancer is unique from other cancers and supports further clinical investigation of therapeutics targeting the MAPK pathway.
Data from SETD2 loss and ATR inhibition synergize to promote cGAS signaling and immunotherapy response in renal cell carcinoma
Authors: Liu Xian-De , Zhang Yan-Ting , McGrail Daniel J. , Zhang Xuesong , Lam Truong , Hoang Anh , Hasanov Elshad , Manyam Ganiraju , Peterson Christine B. , Zhu Haifeng , Kumar Shwetha V. , Akbani Rehan , Pilie Patrick G. , Tannir Nizar M. , Peng Guang , Jonasch Eric
Published: September 2024

Abstract
Purpose: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance the response. Experimental Design: We investigated the effects of SET domain-containing protein 2 (SEDT2) loss on the DNA damage response pathway, the cytosolic DNA sensing pathway, the tumor immune microenvironment, and the response to Ataxia telangiectasia and rad3 related (ATR) and checkpoint inhibition in RCC. Results: ATR inhibition activated the cyclic GMP–AMP synthase (cGAS)-Interferon regulatory factor 3 (IRF3)-dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory cytokines and immune checkpoints. Among the common RCC genotypes, SETD2 loss is associated with preferential ATR activation and sensitizes cells to ATR inhibition. SETD2 knockdown promoted the cytosolic DNA sensing pathway in response to ATR inhibition. Treatment with the ATR inhibitor VE822 concurrently upregulated immune cell infiltration and immune checkpoint expression in Setd2 knockdown Renca tumors, providing a rationale for ATR inhibition plus ICB combination therapy. Setd2 deficient Renca tumors demonstrated greater vulnerability to ICB monotherapy or combination therapy with VE822 than Setd2 proficient tumors. Moreover, SETD2 mutations were associated with a higher response rate and prolonged overall survival in ICB-treated RCC patients but not in non-ICB-treated RCC patients. Conclusions: SETD2 loss and ATR inhibition synergize to promote cGAS signaling and enhance immune cell infiltration, providing a mechanistic rationale for the combination of ATR and checkpoint inhibition in RCC patients with SETD2 mutations.
Data from Single-cell RNA analysis reveals cell-intrinsic functions of CAR-T cells correlating with response in a phase II study of lymphoma patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: September 2024

Abstract
Purpose: Although CD19 CAR-T cell therapy has shown remarkable success in B cell malignancies, a substantial fraction of patients does not obtain a long-term clinical response. This could be influenced by the quality of the individual CAR-T infusion product. To shed some light on this, clinical outcome was correlated to characteristics of CAR-T cell infusion products. Patients and Methods: In this phase II study patients with B cell lymphoma (n=23) or leukemia (n=1) received one or two infusions of third generation CD19-directed CAR-T cells (2x108/m2). The clinical trial was registered at clinicaltrials.gov: NCT03068416. We investigated the transcriptional profile of individual third generation CD19 CAR-T infusion products using targeted single-cell RNA sequencing and multicolor flow cytometry. Results: Two CAR-T infusions were not better than one in the settings used in this study. As for the CAR-T infusion products we found that effector-like CD8+CAR-T cells with a high polyfunctionality, high cytotoxic and cytokine production profile and low dysfunctional signature was associated with clinical response. An extended ex vivo expansion time during CAR-T manufacturing negatively influenced the proportion of effector CD8+CAR-T cell in the infusion product. Conclusions: We identified cell-intrinsic characteristics of effector CD8+CAR-Ts correlating with response that could be used as an indicator for clinical outcome. The results in the study also serves as a guide to CAR-T manufacturing practices.
Data from Tumor microenvironment modifications induced by afatinib in squamous cell carcinoma of the head and neck - a window-of-opportunity study (EORTC90111-24111)
Authors: Beyaert Simon P. , Loriot Axelle E. , Huyghe Nicolas D. , Goebbels Rose M. , Mendola Antonella , Govaerts Anne-Sophie , Fortpied Catherine , Baldin Pamela , Licitra Lisa F. , Lalami Yassine , Clement Paul M. , Machiels Jean-Pascal H. , Schmitz Sandra
Published: September 2024

Abstract
Purpose: The EORTC-90111-24111 phase II window study evaluated afatinib versus no preoperative treatment in patients with primary squamous cell carcinoma of the head and neck (HNSCC). We investigated afatinib-induced tumor and microenvironment modifications by comparing pre- and post-treatment tumor biopsies. Patients and methods: Thirty treatment-naïve patients with primary HNSCC were randomized. Twenty-five patients received afatinib for 14 days before surgery (40mg 1x/day) and five patients were attributed to the control arm. Biopsies were taken at work-up and during surgery. Good quality RNA samples were used for omics analyses. The control arm was enlarged by samples coming from our previous similar window study (Schmitz et al. 2013). Results: Immunohistochemistry analyses of afatinib-treated tumor biopsies showed a decrease in pEGFR (P≤.05) and pERK (P≤.05); an increase in CD3+ (P≤.01) and CD8+ (P≤.01) T-cell infiltration, and in CD3+ (P≤.05) T-cell density. RNA sequencing analyses of afatinib-treated tumor samples showed upregulation of inflammatory genes and increased expression scores of signatures predictive of response to PD-1 blockade (P≤.05). In post-treatment biopsies of afatinib-treated patients, two clusters were observed. Cluster 1 showed a higher expression of markers and gene sets implicated in epithelial-to-mesenchymal transition (EMT) and activation of cancer-associated fibroblasts (CAFs) compared to cluster 2 and controls. Conclusion: Short-term treatment with afatinib in primary HNSCC induces CD3+ and CD8+ tumor infiltration and, in some patients, EMT and CAFs activation. These results open perspectives to overcome resistance mechanisms to anti-HER therapy and to potentiate the activity of immune checkpoint inhibitors.
Data from Preclinical efficacy of LP-184, a tumor site activated synthetic lethal therapeutic, in glioblastoma
Authors: Lal Bachchu , Kulkarni Aditya , McDermott Joseph , Rais Rana , Alt Jesse , Wu Ying , Lopez-Bertoni Hernando , Sall Sophie , Kathad Umesh , Zhou Jianli , Slusher Barbara S. , Bhatia Kishor , Laterra John
Published: September 2024

Abstract
Purpose: Glioblastoma (GBM), is the most common brain malignancy with median survival <2 yrs. Standard-of-care temozolomide (TMZ) has marginal efficacy in ~70% of patients due to MGMT expression. LP-184 is an acylfulvene-derived prodrug activated by the oxidoreductase PTGR1 that alkylates at N3-adenine, not repaired by MGMT. This paper examines LP-184 efficacy against preclinical GBM models and identifies molecular predictors of efficacy in clinical GBM. Experimental Design: LP-184 effects on GBM cell viability and DNA damage were determined using cell lines, primary patient-derived cells and neurospheres. GBM cell sensitivities to LP-184 relative to TMZ and MGMT expression were examined. Pharmacokinetics and CNS bioavailability were evaluated in mice with GBM xenografts. LP-184 effects on GBM xenograft growth and animal survival were determined. Machine learning, bioinformatic tools and clinical databases identified molecular predictors of LP-184 responsiveness. Results: LP-184 inhibited viability of multiple GBM cell isolates including TMZ-resistant and MGMT-expressing cells at IC50 = ~22-310 nM. Pharmacokinetics showed favorable AUCbrain/plasma and AUCtumor/plasma ratios of 0.11 (brain Cmax=839 nM) and 0.2 (tumor Cmax = 2,530 nM), respectively. LP-184 induced regression of GBM xenografts and prolonged survival of mice bearing orthotopic xenografts. Bioinformatic analyses identified PTGR1 elevation in clinical GBM subtypes and associated LP-184 sensitivity with EGFR signaling, low nucleotide excision repair (NER) and low ERCC3 expression. Spironolactone, that induces ERCC3 degradation, decreased LP-184 IC50 3-6 fold and enhanced GBM xenograft anti-tumor responses. Conclusions: These results establish LP-184 as a promising chemotherapeutic for GBM with enhanced efficacy in intrinsic or spironolactone-induced TC-NER deficient tumors.
Data from Diagnostic Performance of a Tumor Marker Gene Test to Personalize Serum CA19-9 Reference Ranges
Authors: Dbouk Mohamad , Abe Toshiya , Koi Chiho , Ando Yohei , Saba Helena , Abou Diwan Elizabeth , Macgregor-Das Anne , Blackford Amanda L. , Mocci Evelina , Beierl Katie , Dbouk Ali , He Jin , Burkhart Richard , Lennon Anne Marie , Sokoll Lori , Canto Marcia Irene. , Eshleman James R. , Goggins Michael
Published: September 2024

Abstract
Purpose: CA19-9 synthesis is influenced by common variants in the fucosyltransferase (FUT) enzymes FUT3 and FUT2. We developed a clinical test to detect FUT variants and evaluated its diagnostic performance for pancreatic ductal adenocarcinoma (PDAC). Experimental Design: A representative set of controls from the Cancer of the Pancreas Screening study was identified for each FUT functional group. Diagnostic sensitivity was determined first in a testing set of 234 PDAC cases, followed by a 134-case validation set, all of whom had undergone resection with curative intent without neoadjuvant therapy. Tumor marker gene testing was performed in the Johns Hopkins Molecular Diagnostic Laboratory. CA19-9 levels were measured in the Hopkins Clinical Chemistry lab. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative ability of CA19-9 alone versus with the gene test. Results: Applying the CA19-9 standard cutoff (<36U/ml) to all 716 subjects yielded a 68.8% sensitivity in the test set of cases, 67.2% in the validation set, at 91.4% specificity. Applying 99th percentile cut-offs according to each individual’s FUT group, (3, 34.9, 41.8, and 89.2, for the FUT3-null, FUT-low, FUT-intermediate, and FUT-high groups, respectively), yielded a diagnostic sensitivity for CA19-9 in the first set of cases of 66.7%, 65.7% in the validation set, at 98.9% specificity. ROC analysis for CA19-9 alone yielded an area under the curve (AUC) of 0.84; with the tumor marker gene test, AUC improved to 0.92 (p<0.001). Conclusion: Using a tumor marker gene test to personalize an individual’s CA19-9 reference range significantly improves diagnostic accuracy.
Data from Axicabtagene Ciloleucel in Combination With the 4-1BB Agonist Utomilumab in Patients With Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results From ZUMA-11
Authors: Jain Michael D. , Miklos David B. , Jacobson Caron A. , Timmerman John M. , Sun Jennifer , Nater Jenny , Fang Xiang , Patel Ankit , Davis Madison , Heeke Darren , Trinh Tan , Mattie Mike , Neumann Frank , Kim Jenny J. , To Christina , Filosto Simone , Reshef Ran
Published: September 2024

Abstract
Purpose: Chimeric antigen receptor (CAR) T-cell therapies have shown clinical benefit for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), yet approximately 60% of patients do not respond or eventually relapse. We investigated the safety and feasibility of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) in combination with the 4-1BB agonist antibody utomilumab as an approach to improve efficacy of CAR T-cell therapy. Methods: In Phase 1 of the single-arm ZUMA-11 trial, patients with R/R LBCL received a single axi-cel infusion (target dose: 2×106 cells/kg) plus utomilumab 10–200 mg intravenously every 4 weeks for up to 6 months in a dose-escalation design. The primary endpoint was incidence of dose-limiting toxicities (DLTs) with utomilumab. Key secondary endpoints were safety, antitumor activity, pharmacokinetics, and pharmacodynamics. Results: No DLTs were observed among patients treated with axi-cel and utomilumab (n=12). Grade ≥3 adverse events occurred in 10 patients (83%); none were Grade ≥3 cytokine release syndrome or neurologic events. The objective response rate was 75% and 7 patients (58%) had a complete response. Peak CAR T-cell levels increased in a utomilumab dose-dependent manner up to 100 mg. Patients who received utomilumab 100 mg had persistently increased CAR T cells on Days 57–168 compared with other dose levels. Utomilumab was associated with dose-dependent increases in IL-2, IFNγ, and IL-10. Conclusions: Utomilumab-mediated 4-1BB agonism combined with axi-cel therapy had a manageable safety profile. Dual 4-1BB and CD28 costimulation is a feasible therapeutic approach that may enhance CAR T-cell expansion in patients with LBCL.
Data from Urinary tumor DNA MRD analysis to identify responders to neoadjuvant immunotherapy in muscle-invasive bladder cancer
Authors: Zhang Ruiyun , Zang Jingyu , Jin Di , Xie Feng , Shahatiaili Akezhouli , Wu Guangyu , Zhang Lu , Wang Lu , Zhang Yue , Zhao Zhixin , Du Pan , Jia Shidong , Fan Jinhai , Zhuang Guanglei , Chen Haige
Published: September 2024

Abstract
Purpose: Bladder preservation is a viable option for some muscle-invasive bladder cancer (MIBC) patients, but an effective noninvasive biomarker test to accurately identify promising candidates is lacking. Here we present the clinical application of a novel tissue-agnostic, urine-based minimal residual disease (MRD) assay in the neoadjuvant setting for personalized disease surveillance and actionable target identification to facilitate bladder-sparing treatment approaches. Patients and Methods: The urinary tumor DNA (utDNA) analysis was evaluated in an investigator-initiated phase I trial RJBLC-I2N003 in which 20 patients diagnosed with resectable MIBC were treated presurgically with the PD-1 inhibitor toripalimab followed by radical cystectomy (RC). Results: We showed that neoadjuvant toripalimab therapy was feasible, safe, and induced a 40% rate (8/20) of pathological complete response. Longitudinal utDNA profiling outperformed radiographic assessment and conventional biomarkers to predict the pathologic outcome of immune checkpoint blockade. In addition to detecting 3 exceptional responders with molecular MRD-negative status, we identified 7 other individuals characterized for utDNA clearance and 4 harboring FGFR3 mutants, all of whom (60%, 12/20) could have postponed or avoided RC. Conclusions: These findings demonstrate the safety and efficacy of neoadjuvant toripalimab, and suggest the immense potential of noninvasive utDNA MRD testing to guide tailored decision-making with regard to bladder preservation and change the current treatment paradigm for MIBC patients.
Data from Depth of radiographic response (DpR) and time to tumor regrowth (TTG) predicts overall survival following anti-VEGF therapy in recurrent glioblastoma
Authors: Ellingson Benjamin M. , Hagiwara Akifumi , Morris Connor J. , Cho Nicholas S. , Oshima Sonoko , Sanvito Francesco , Oughourlian Talia C. , Telesca Donatello , Raymond Catalina , Abrey Lauren E. , Garcia Josep , Aftab Dana T. , Hessel Colin , Rachmilewitz Minei Tamar , Harats Dror , Nathanson David A. , Wen Patrick Y. , Cloughesy Timothy F.
Published: September 2024

Abstract
Purpose. Anti-angiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In the current study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with anti-angiogenic therapy. Experimental Design. N=276 patients in two phase II trials were used as training data, including bevacizumab +/- irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N=74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival. Results: Optimized thresholds occurred at g=0.07months-1 (phase II:HR=0.2579,P=5x10-20; phase III:HR=0.2197, P=5x10-5); d=0.11months-1 (HR=0.3365, P<0.0001; HR=0.3675,P=0.0113); TTG=3.8 months (HR=0.2702,P=6x10-17;HR=0.2061,P=2x10-5); and DpR=11.3% (HR=0.6326,P=0.0028;HR=0.4785, P=0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pre-treatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth. Conclusions: Recurrent glioblastoma patients with a large, durable radiographic response to anti-angiogenic agents have significantly longer survival. This information is useful for interpreting activity of anti-angiogenic agents in recurrent glioblastoma.
Data from Safety, immunologic and clinical activity of Durvalumab in combination with Olaparib or Cediranib in advanced leiomyosarcoma: Results of the DAPPER clinical trial
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar. , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R.
Published: September 2024

Abstract
Purpose: Non-inflamed (cold) tumors such as leiomyosarcoma (LMS) do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis-, or poly-ADP ribose polymerase (PARP) inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pre-treated LMS patients. Patients and Methods: Patients were randomized to receive durvalumab 1500mg IV q4w with either Olaparib 300mg bid PO (Arm A) or Cediranib 20mg qd PO on 5 days/week (Arm B) until unacceptable toxicity or disease progression. Paired tumor biopsies, serial radiological assessments and stool collections were performed. Primary endpoints were safety, and immune cell changes in the TME. Objective responses and survival were correlated with transcriptomic, radiomic and microbiome parameters. Results: Among 30 heavily pre-treated patients (15 on each arm), grade ≥ 3 toxicity occurred in 3 (20%) and 2 (13%) on Arms A and B, respectively. On arm A, 1 patient achieved partial response (PR) with increase in CD8 T-cells and macrophages in the TME during treatment, while 4 had stable disease ≥ 6 months (SD-6m). No patients on Arm B achieved PR or SD-6m. Transcriptome analysis showed that baseline M1-macrophage and B-cell activity were associated with overall survival. Conclusions: Durvalumab plus olaparib increased immune cell infiltration of TME with clinical benefit in some LMS patients. Baseline M1-macrophage and B-cell activity may identify LMS patients with favorable outcomes on immunotherapy and should be further evaluated.
Data from Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer
Authors: Thummalapalli Rohit , Ricciuti Biagio , Bandlamudi Chaitanya , Muldoon Daniel , Rizvi Hira , Elkrief Arielle , Luo Jia , Alessi Joao V. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Hong Lingzhi , Zhang Jianjun , Heymach John V. , Gibbons Don L. , Plodkowski Andrew J. , Ravichandran Vignesh , Donoghue Mark T.A. , Vanderbilt Chad , Ladanyi Marc , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Chaft Jamie E. , Hellmann Matthew D. , Vokes Natalie I. , Awad Mark M. , Schoenfeld Adam J.
Published: September 2024

Abstract
Purpose: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICIs), and how these might differ from features predictive of short-term response (STR). Experimental Design: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs over ten years. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor PD-L1 expression, mutational burden (TMB), next-generation sequencing, and whole exome sequencing data were analyzed to identify characteristics enriched in patients achieving LTR compared to STR and non-LTR. Results: Among 3118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival of 81% and 18% among LTR and STR patients respectively. High TMB (≥ 50th percentile) enriched for LTR compared to STR (P = 0.001) and non-LTR (P < 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared to non-LTR (P < 0.001); PD-L1 ≥ 50% did not enrich for LTR compared to STR (P = 0.181). Non-squamous histology (P = 0.040) and increasing depth of response (median best overall response [BOR] -65% vs -46%, P < 0.001) also associated with LTR compared to STR; no individual genomic alterations were uniquely enriched among LTR patients. Conclusions: Among advanced NSCLC patients treated with ICIs, distinct features including high TMB, non-squamous histology, and depth of radiographic improvement distinguish patients poised to achieve long-term response compared to initial response followed by progression, whereas high PD-L1 does not.
Data from Analysis of tumor microenvironment changes after neoadjuvant chemotherapy with or without bevacizumab in advanced ovarian cancer (GEICO-89T/MINOVA study).
Authors: Tavira Beatriz , Iscar Teresa , Manso Luis , Santaballa Ana , Gil-Martin Marta , García García Yolanda , Romeo Margarita , Iglesias Maria , de Juan Ferré Ana , Barretina-Ginesta Maria Pilar , Manzano Aránzazu , Gaba Lydia , Rubio María Jesús , de Andrea Carlos E. , González-Martín Antonio
Published: September 2024

Abstract
Purpose: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. Experimental Design: Immunohistochemistry and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 ovarian cancer patients enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. Results: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells and an upregulation effector/regulatory cells ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophages-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significative associated with PFS. Conclusions: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at cellular level, changes in CD4+, CD8+lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. Based on our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first line of advanced EOC.
GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression
Authors: Stacchiotti Silvia , Martini Silvia , Pasquali Sandro , Frezza Anna M. , Beretta Alessia , Percio Stefano , Lecchi Mara , Tortoreto Monica , Barisella Marta , Collini Paola , Dagrada Gian Paolo , Merlini Alessandra , Huang Paul H. , Jenks Andrew , Jones Robin L. , Tap William D. , Ingrosso Matilde , Morosi Carlo , Brich Silvia , Giani Claudia , Verderio Paolo , Casali Paolo G. , Leonard Hugh , Gronchi Alessandro , Zuco Valentina , Zaffaroni Nadia
Published: September 2024

Purpose:

Epithelioid hemangioendothelioma (EHE), an ultra-rare sarcoma, poses therapeutic challenges because of limited efficacy of conventional chemotherapy in advanced cases, necessitating exploration of new treatment avenues and identification of novel aggressive biomarkers. This study aimed at (i) utilizing a patient-derived xenograft model of EHE and its associated cell line to assess the efficacy of sirolimus and (ii) analyzing two distinct patient cohorts to pinpoint circulating biomarkers of EHE aggressiveness.

Experimental Design:

A patient-derived xenograft model and corresponding cell line were established from a patient with advanced EHE, demonstrating consistency with the original tumor in terms of histomorphology, WWTR1::CAMTA1 fusion presence, and genomic and transcriptomic profiles. Two independent patient series were employed to investigate the association between growth/differentiation factor 15 (GDF-15) serum levels and EHE aggressiveness.

Results:

ELISA analyses on EHE cell culture medium and blood from EHE-carrying mice revealed the release of GDF-15 by EHE cells. Sirolimus exhibited markedly higher antitumor activity compared with doxorubicin, concurrently reducing GDF-15 expression/release both in vivo and in vitro. This reduction was attributed to the drug-induced inhibition of phosphorylation/activation of 4E-BP1 and subsequent downregulation of the GDF-15 transcription factors ATF4 and ATF5. Blood sample analyses from two independent patient series showed a significant correlation between GDF-15 and EHE aggressiveness.

Conclusions:

This study identifies GDF-15 as a novel biomarker of EHE aggressiveness and underscores the superior efficacy of sirolimus compared with doxorubicin in our experimental models. The observed inhibition of GDF-15 release by sirolimus suggests its potential as a biomarker for monitoring the drug’s activity in patients.
Predictive and Dynamic Signature for Antiangiogenics in Combination with a PD1 Inhibitor in Soft-Tissue Sarcoma: Correlative Studies Linked to the IMMUNOSARC Trial
Authors: Moura David S. , Lopez-Marti Jesus M. , Benesova Iva , de Andrea Carlos , di Lernia Davide , Lacerenza Serena , Mondaza-Hernandez Jose L. , Martin-Ruiz Marta , Ramirez-Calvo Marta , Grignani Giovanni , Martinez-Trufero Javier , Redondo Andres , Valverde Claudia , Stacchiotti Silvia , Lopez-Pousa Antonio , Lopez-Guerrero José A. , Gutierrez Antonio , Encinas-Tobajas Victor , Hindi Nadia , Sangiolo Dario , Lopez-Martin Jose A. , Strizova Zuzana Ozaniak , Martin-Broto Javier
Published: September 2024

Purpose:

The IMMUNOSARC trial combined an antiangiogenic agent (sunitinib) with a PD1 inhibitor (nivolumab) in advanced sarcomas. Here, we present the first correlative studies of the soft-tissue sarcoma cohort enrolled in this trial.

Experimental Design:

Formalin-fixed paraffin-embedded and peripheral blood samples were collected at baseline and week 13. Formalin-fixed paraffin-embedded samples were used for transcriptomics and multiplex immunofluorescence, whereas peripheral blood samples were used for multiplexed immunoassays. Flow cytometry and Luminex assays were performed to validate translational findings in tumor-isolated cells and peripheral blood mononuclear cells derived from patients.

Results:

The density of intratumoral CD8+ T cells, measured by multiplexed immunophenotyping, was significantly increased after treatment. This augment was accompanied by the dynamic significant increase in the gene expressions of CD86, CHI3L1, CXCL10, CXCL9, LAG3, and VCAM1 and the decrease in the expression levels of NR4A1. In peripheral blood, 12 proteins were significantly modulated by treatment at week 13. A score integrating the dynamic expression of the 7 genes and the 12 soluble factors separated 2 groups with distinct progression-free survival (PFS): 4.1 months [95% confidence interval, 3.5–not reached (NR)] versus 17 months (95% confidence interval, 12.0–NR), P = 0.014. This molecular score was predictive of PFS when applied to the normalized data determined in the baseline samples.

Conclusions:

Treatment with sunitinib and nivolumab inflamed the sarcoma microenvironment, increasing CD8+ T-cell density and the expression of several genes/proteins with relevance in the response to PD1 inhibitors. A molecular signature identified two groups of patients with distinct PFS for the combination of antiangiogenics plus PD1 inhibitor therapy.
Supplementary Data from IMiDs augment CD3-bispecific antibody induced CD8+ cell cytotoxicity and expansion by enhancing IL-2 production
Authors: Li Ji , Slaga Dionysos , Johnston Jennifer , Junttila Teemu T.
Published: September 2024

Supplementary Data
Supplementary Table S1 from Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib Plus Osimertinib in an EGFR-Mutation Positive, MET-Amplified Non-Small Cell Lung Cancer Model
Authors: Jones Rhys D.O. , Petersson Klas , Tabatabai Areya , Bao Larry , Tomkinson Helen , Schuller Alwin G.
Published: September 2024

Supplementary Table S1
Supplementary Materials and Methods from Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib Plus Osimertinib in an EGFR-Mutation Positive, MET-Amplified Non-Small Cell Lung Cancer Model
Authors: Jones Rhys D.O. , Petersson Klas , Tabatabai Areya , Bao Larry , Tomkinson Helen , Schuller Alwin G.
Published: September 2024

Supplementary Data text
Supplementary Table 1 from Novel arginase inhibitor, AZD0011, demonstrates immune cell stimulation and anti-tumor efficacy with diverse combination partners
Authors: Doshi Aatman S. , Cantin Susan , Hernandez Marylens , Srinivasan Srimathi , Tentarelli Sharon , Griffin Matthew , Wang Yanjun , Pop-Damkov Petar , Prickett Laura B. , Kankkonen Cecilia , Shen Minhui , San Martin Maryann , Wu Song , Castaldi M Paola , Ghadially Hormas , Varnes Jeffrey , Gales Sonya , Henry David , Hoover Clare , Mele Deanna A. , Simpson Iain , Gangl Eric T. , Mlynarski Scott N. , Finlay M. Raymond V. , Drew Lisa , Fawell Stephen E. , Shao Wenlin , Schuller Alwin G.
Published: September 2024

Supplementary Table 1
Supplementary Figure 20 from Arginase 1/2 inhibitor OATD-02: from discovery to first-in-man setup in cancer immunotherapy
Authors: Borek Bartlomiej , Nowicka Julita , Gzik Anna , Dziegielewski Marek , Jedrzejczak Karol , Brzezinska Joanna , Grzybowski Marcin , Stanczak Paulina , Pomper Paulina , Zagozdzon Agnieszka , Rejczak Tomasz , Matyszewski Krzysztof , Golebiowski Adam , Olczak Jacek , Lisiecki Kamil , Tyszkiewicz Magdalena , Kania Magdalena , Piasecka Sylwia , Cabaj Anna , Dera Paulina , Mulewski Krzysztof , Chrzanowski Jacek , Kusmirek Damian , Sobolewska Elzbieta , Magdycz Marta , Mucha Lukasz , Masnyk Marek , Golab Jakub , Nowotny Marcin , Nowak Elzbieta , Napiorkowska-Gromadzka Agnieszka , Pikul Stanislaw , Jazwiec Radoslaw , Dzwonek Karolina , Dobrzanski Pawel , Meyring Michael , Skowronek Krzysztof , Iwanowski Piotr , Zaslona Zbigniew , Blaszczyk Roman
Published: September 2024

Allometric scaling of human plasma clearance (CL-NAS)
Supplementary Figure 16 from Arginase 1/2 inhibitor OATD-02: from discovery to first-in-man setup in cancer immunotherapy
Authors: Borek Bartlomiej , Nowicka Julita , Gzik Anna , Dziegielewski Marek , Jedrzejczak Karol , Brzezinska Joanna , Grzybowski Marcin , Stanczak Paulina , Pomper Paulina , Zagozdzon Agnieszka , Rejczak Tomasz , Matyszewski Krzysztof , Golebiowski Adam , Olczak Jacek , Lisiecki Kamil , Tyszkiewicz Magdalena , Kania Magdalena , Piasecka Sylwia , Cabaj Anna , Dera Paulina , Mulewski Krzysztof , Chrzanowski Jacek , Kusmirek Damian , Sobolewska Elzbieta , Magdycz Marta , Mucha Lukasz , Masnyk Marek , Golab Jakub , Nowotny Marcin , Nowak Elzbieta , Napiorkowska-Gromadzka Agnieszka , Pikul Stanislaw , Jazwiec Radoslaw , Dzwonek Karolina , Dobrzanski Pawel , Meyring Michael , Skowronek Krzysztof , Iwanowski Piotr , Zaslona Zbigniew , Blaszczyk Roman
Published: September 2024

PK and PD effects after intravenous administration of OATD-02 and CB-1158 in Sprague-Dawley rats
Supplementary Table 1 from BET inhibition sensitizes immunologically-cold Rb-deficient prostate cancer to immune checkpoint blockade
Authors: Olson Brian M. , Chaudagar Kiranj , Bao Riyue , Saha Sweta Sharma. , Hong Christina , Li Marguerite , Rameshbabu Srikrishnan , Chen Raymond , Thomas Alison , Patnaik Akash
Published: September 2024

List of antibodies used in experiments
Supplementary Figure 11 from BET inhibition sensitizes immunologically-cold Rb-deficient prostate cancer to immune checkpoint blockade
Authors: Olson Brian M. , Chaudagar Kiranj , Bao Riyue , Saha Sweta Sharma. , Hong Christina , Li Marguerite , Rameshbabu Srikrishnan , Chen Raymond , Thomas Alison , Patnaik Akash
Published: September 2024

Androgen deprivation increases the frequency of infiltrating T cells and M1 tumor-associated macrophages in the tumor microenvironment.
Supplementary Figure S3 from Tyrosine Kinase Inhibitors Diminish Renal Neoplasms in a Tuberous Sclerosis Model via induction of Apoptosis
Authors: Unachukwu Uchenna , Sonett Jarrod , Woode Denzel , Shiomi Takayuki , Chada Kiran , D'Armiento Jeanine M.
Published: September 2024

Ingenuity Pathway Analysis of Drug-Induced Renal Angiomyolipoma Cells (p-values)
Supplementary Table S1 from Efficacy and Imaging Enabled Pharmacodynamic Profiling of KRAS G12C Inhibitors in Xenograft and Genetically Engineered Mouse Models of Cancer
Authors: Lee Catherine , Jiang Ziyue Karen , Planken Simon , Manzuk Lisa K. , Ortiz Roberto , Hall Michael , Noorbehesht Kavon , Ram Sripad , Affolter Timothy , Troche Gabriel E. , Ihle Nathan T. , Johnson Theodore , Ahn Youngwook , Kraus Manfred , Giddabasappa Anand
Published: September 2024

Comparative activity data for Compound A and sotorasib
Supplementary Figure S4 from Efficacy and Imaging Enabled Pharmacodynamic Profiling of KRAS G12C Inhibitors in Xenograft and Genetically Engineered Mouse Models of Cancer
Authors: Lee Catherine , Jiang Ziyue Karen , Planken Simon , Manzuk Lisa K. , Ortiz Roberto , Hall Michael , Noorbehesht Kavon , Ram Sripad , Affolter Timothy , Troche Gabriel E. , Ihle Nathan T. , Johnson Theodore , Ahn Youngwook , Kraus Manfred , Giddabasappa Anand
Published: September 2024

Baseline differences in tumor progression and histopathology of G12D versus G12C KP GEM models
Supplementary Table S16 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E-based Antibody-Drug Conjugate for treatment of Nectin-4-expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: September 2024

Summary of pharmacokinetics studies in 9MW2821 and enfortumab vedotin in tumor-bearing mice