bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTIM-01. NIVOLUMAB AND STEREOTACTIC RADIOSURGERY (SRS) FOR PATIENTS WITH BREAST CANCER BRAIN METASTASES: LONG TERM RESULTS AND CELL FREE DNA (CFDNA) ASSESSMENT FROM A NON-RANDOMIZED, OPEN-LABEL, PHASE IB STUDY
Authors: Ahmed Kamran , Kim Youngchul , Arrington John , Kim Sungjune , DeJesus Michelle , Soyano Aixa , Armaghani Avan , Costa Ricardo , Khong Hung , Loftus Loretta , Rosa Marilin , Caudell Jimmy , Diaz Roberto , Etame Arnold , Tran Nam , Soliman Hatem , Czerniecki Brian , Forsyth Peter , Yu Hsiang-Hsuan Michael , Han Hyo 
Published: November 2023

Abstract

BACKGROUND
We hypothesized treatment with nivolumab and SRS would be feasible and well tolerated and may improve intracranial tumor control over SRS alone for breast cancer brain metastases.

METHODS
The study is a phase Ib trial of nivolumab and SRS for breast cancer brain metastases. Clinical trial information: NCT03807765. Key eligibility criteria include breast cancer brain metastases of all subtypes, age ≥ 18, ECOG ≤ 2 with ≥ 10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg IV) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. Blood was collected at baseline and q4 weeks.

RESULTS
A total of 12 patients were treated to 17 brain metastases. Breast cancer subtypes included triple negative (50%), HR+/HER2- (33%), and HR-/HER2+ (17%). Median follow-up from start of protocol therapy is 44 months. Two lesions were noted to undergo local failure, both pathologically confirmed, for a 12-month local control of 94%. Median distant intracranial control was 7.4 months with a 12 month control rate of 33%. Median systemic progression free survival was 7.7 months with a 12 month rate of 42%. Median overall survival (OS) was 24.7 months with a 12 month OS of 75%. No cases of radionecrosis were noted. Most patients were noted to have an increase in cfDNA throughout study treatment, at week 5 compared to baseline (83%), week 25 compared to baseline (89%), and 100% at first follow-up. An increase in cfDNA 4 weeks post SRS was found to predict worse intracranial control (HR: 4.4; 95% CI: 1.1-18.5; p = 0.04).

CONCLUSIONS
Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. An increase in cfDNA 4 weeks post SRS was found to predict worse intracranial control and was eventually seen in all patients.
CTIM-04. TOPICAL DIPHENCYPRONE IMMUNOTHERAPY FOR CUTANEOUS NEUROFIBROMAS ASSOCIATED WITH NF1, A PHASE 1 STUDY
Authors: Brown Rebecca , Gulati Nicholas , Poplauski Dina , Young Jade 
Published: November 2023

Abstract
Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome affecting ~1 in 2500 people. Affected patients develop peripheral nerve sheath tumors of the skin known as cutaneous neurofibromas (CN), with variable disease burden ranging from 0-1 tumors to over 10,000. Patients cite deformity, pain, and pruritus from CN as one of the most difficult features of the disease. To date, there are no practical or effective pharmacotherapies for these tumors. This is a single-center, phase I, open label trial to evaluate the safety, tolerability, and efficacy of diphencyprone (DPCP), a topical hapten compound that induces a delayed-type. Twelve adult patients with NF1 and &gt;3 CN of maximum diameter &gt;4 mm were enrolled. DPCP 0.04% ointment was administered topically once weekly to up to 20 cNFs in a localized body region for 10 weeks. Endpoints included (primary) safety and tolerability of DPCP ointment via CTCAE reporting and subjective scoring of symptoms. Efficacy was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) guidelines in conjunction with whole body photography and manual tri-axial tumor measurements. One treated tumor is tracked throughout the study with optical coherence tomography (OCT) imaging. Skin biopsies of a CN and surrounding tissue are collected at baseline, on Day 17 after treatment initiation, and four weeks post-treatment for exploratory endpoints qRT-PCR, single-cell RNA sequencing, and immunohistochemistry to detect differences in immune cell infiltration, tumor cell density, and transcriptional changes throughout the treatment course. Clinical trial information: NCT05438290.
CTIM-08. LOCAL IMMUNOTHERAPY WITH AUTOLOGOUS CIK CELLS FOR HIGH GRADE GLIOMAS: A PILOT STUDY WITH 20 YEARS FOLLOW-UP AND FAVORABLE FACTORS FOR LONG-TERM SURVIVAL
Authors: Duan Hao , He Zhenqiang , Chen Zhongping , Mou Yonggao 
Published: November 2023

Abstract

BACKGROUND
Between November 2002 and March 2004, a pilot study was conducted to evaluate the tolerance and survival following local administration of autologous cytokine-induced killer (CIK) cells through Ommaya reservoirs implanted into the tumor resection cavity in 6 patients with high grade glioma (HGG) at Sun Yat-sen University Cancer Center.

METHODS
We reviewed the clinicopathological characteristics of these patients and updated their long-term follow-up. Profiles of tumor genome, transcriptome and immune microenvironment were also investigated by genomic target sequencing, RNA sequencing, electrochemiluminescence assay and immunohistochemistry (IHC) staining.

RESULTS
Four patients died from tumor progression and their overall survival ranged from 10.0 to 33.9 months. Remarkably, 2 patients, including one diagnosed as astrocytoma (IDH1 mutation, WHO 3) and the other diagnosed as diffuse hemispheric glioma H3 G34-mutant (G34-DHG), survived more than 19 years without evidence of recurrence. The distinctive clinical feature of the 2 long-term survivors was tumor gross total resection (GTR) before CIK therapy. Comparing with the short-term survivors, NTRK1 mutation was uniquely present and 353 genes were differentially expressed in the long-term survivors. These differential expression genes were highly associated with immune function. Electrochemiluminescence assay and IHC staining revealed higher expressions of cytokines and lower infiltrations of tumor-associated macrophages in the tumors of the long-term survivors.

CONCLUSION
These findings suggest that certain HGG patients can acquire long-term survival after local immunotherapy with CIK cells. Tumor GTR before CIK therapy and relatively weaker immunosuppressive tumor microenvironment may be the favorable factors for long-term survival.
CTIM-09. PHASE 1/1B TRIAL OF FC-ENGINEERED ANTI-CD40 AGONIST MONOCLONAL ANTIBODY (2141-V11) INFUSED WITH D2C7-IT IN ENHANCING DISEASE BY CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (RMG)
Authors: Desjardins Annick , Chandramohan Vidya , Landi Daniel , Peters Katherine , Johnson Margaret O , Low Justin , Khasraw Mustafa , Threatt Stevie , Bullock Chevelle , Herndon James , Lipp Eric , Friedman Allan , Friedman Henry , Ashley David , Osorio Juan , Ravetch Jeffrey , Bigner Darell 
Published: November 2023

Abstract

BACKGROUND
D2C7-IT is a dual-specific immunotoxin. Recombinant antibody fragments bind the wild-type epidermal growth factor receptor (EGFRwt) and its mutant EGFR variant III (EGFRvIII), triggering internalization and intracellular delivery of the Pseudomonas exotoxin, D2C7-IT cell-killing component. Single intratumoral delivery of D2C7-IT in animals generates an antitumor response by directly killing tumor cells and indirectly activating an adaptive T-cell response. However, tumor-associated macrophages (TAMs)-mediated immunosuppression limits its efficacy. Eliminating MG immunosuppression via CD40 co-stimulation enhances D2C7-IT-induced antitumor responses by activating a TAMs proinflammatory phenotype and promoting long-term tumor-specific CD8+ T-cell immunity. We initiated a phase 1 trial of D2C7-IT+2141-V11 (Fc-engineered anti-CD40 agonist) administered via CED in rMG patients.

METHODS
Eligibility includes adult patients with solitary supratentorial rMG (WHO grade 3/4); ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; and KPS ≥70%. Cohorts of 3 patients were treated with increasing doses of 2141-V11 to determine the recommended phase 2 dose (RP2D) when administered sequentially following D2C7-IT (166,075ng) via CED. Five dose levels (DLs) were evaluated (2141-V11 at: DL1: 0.70mg; DL2: 2.0mg; DL2**: 3.0mg; DL2*: 4.0mg; DL3: 7.0mg).

RESULTS
As of June 5, 2023, 27 patients had been treated (3 patients on DL1 and DL2; 2 on DL3 and DL2*; 17 on DL2**). No dose-limiting toxicities were observed; however, lower DLs were added due to higher frequency of adverse events (AEs) expected with D2C7-IT+2141-V11 within DL3 and DL2* (fever, neurologic symptoms). 13/27 patients remain alive (range 4-22months after therapy). No grade 4 or 5 AEs related to D2C7-IT+2141-V11 were observed, while grade 3 related AEs include one each of: dysphasia, encephalopathy, headache, hydrocephalus, paresthesia, and pyramidal tract disorder.

CONCLUSIONS
The RP2D for intratumoral infusion of D2C7-IT+2141-V11 via CED is identified. The protocol was amended to evaluate the addition of cervical perilymphatic injections of 2141-V11 post CED of D2C7-IT+2141-V11.
CTIM-10. A SURGICAL WINDOW-OF-OPPORTUNITY CLINICAL TRIAL EVALUATING THE PCSK9 INHIBITOR EVOLOCUMAB IN PATIENTS WITH GLIOMA
Authors: Singh Kirit , Hotchkiss Kelly , Foster Matthew , Railton Chelsea , Blandford Emily , Thomas Elizabeth , Miller Elizabeth S , Ashley David , Desjardins Annick , Friedman Henry , Johnson Margaret O , Friedman Allan , Keir Steve , Herndon James , Sampson John , Li Chuan-Yuan , Fecci Peter , Patel Anoop , Khasraw Mustafa 
Published: November 2023

Abstract
Gliomas evade the immune system by downregulating cell surface expression of major histocompatibility class (MHC)-I. Antagonism of proprotein convertase subtilisin/kexin type 9 (PCSK9) increases MHC-I expression and can enhance checkpoint inhibition in vivo. Evolocumab is an FDA approved monoclonal antibody (mAb) for hyperlipidemia that inhibits PCSK9. However, large constructs such as mAbs typically have limited penetrance across the blood-brain-barrier. We report the preliminary results of a surgical window-of-opportunity study evaluating if Evolocumab administered subcutaneously pre-preoperatively is detectable in tumor tissue from patients with newly diagnosed or recurrent glioma (PESKe; NCT04937413). Twenty contemporaneous control samples are prospectively collected from patients undergoing craniotomy without receiving Evolocumab. Although non-randomized, these specimens provide valuable information for exploratory comparison of the treated and untreated specimens in terms of drug penetrance and MHC-I expression. To date, 24 patients have been enrolled (M: 14, F: 10) with a median age of 46.5. Of these, 5 received pre-procedure subcutaneous Evolocumab (420mg), while the remaining 19 were analyzed as controls. In treated patients, Evolocumab was detectable via mass spectroscopy (LC-MS/MS) in all analyzed cases, including in tumor tissue from both contrast-enhancing and non-contrast-enhancing regions. Ratios of drug in tumor relative to intra-operative blood were markedly higher in samples from contrast-enhancing regions compared to non-contrast enhancing regions (median ratio of tumor to blood of 0.1503 vs 0.0248 respectively). The tumor proteome was also analyzed using LC-MS/MS to quantitate MHC-I and MHC-II proteins. Initial analysis found increased MHC-I (HLA-A, HLA-B, HLA-C) quantitation via mass spectroscopic analysis of the tumor proteome in treated samples compared to contemporaneous untreated controls. No significant adverse events have been reported in those who received pre-procedure Evolocumab. Ongoing analyses will seek to determine whether increased MHC-I quantities in tumor correspond with increased cell surface expression via immunofluorescence and immunohistochemistry.
CTIM-16. DEVELOPING PATIENT SPECIFIC TUMOR INFILTRATING LYMPHOCYTES (TILS) WITH INCREASED TUMOR SPECIFICITY AS A THERAPY FOR GLIOBLASTOMA
Authors: Hotchkiss Kelly , Blandford Emily , Noldner Pamela , Zhou Ying , Singh Kirit , Patel Anoop , Fecci Peter , Antonia Scott , Shaz Beth , Khasraw Mustafa 
Published: November 2023

Abstract
Immunotherapy failure in glioblastoma results from three main hurdles; limited numbers of T cells within the tumor, T cell exhaustion and significant intra-tumoral and intra-patient heterogeneity leading to lack of T cell tumor recognition. Our group has developed an expansion protocol to isolate and expand less exhausted tumor infiltrating lymphocytes (TILs) from the tumor periphery, selecting for TILs that recognize tumor antigen ex vivo. This process will increase the number of T-cells specific for an individual patient’s diverse tumor neoantigens. We have successfully expanded glioblastoma associated TILs from 66% of the novel Lukens trap substrate, which collects TILs and tumor from the tumor periphery. Cells are expanded in two stages, preREP and REP, through novel methods based on a protocol with clinical success in lung cancer and modified to increase the percent of tumor specific T cells. Through co-culture with patient matched glioma neurospheres we have identified activated T cells from each stage of culture (initial product, preREP, REP) based on CD137+ expression and tumor specific cytokine release (IFNy+TNFa+IL2+IL17a+) by flow cytometry. Through 5’scRNA sequencing paired with TCR repertoire analysis we can identify activation specific TCRs. Overrepresented TCR alpha and beta chains will be linked by a P2A site, cloned into a lentiviral vector, and transduced into TCR negative Jurkat cells to confirm tumor reactivity. This strategy will allow us to enrich and assess tumor specific TCR activity compared to bystander activation in our TIL product. Following additional preclinical assessment of cytotoxicity against autologous tumor, we will evaluate safety and feasibility of by administering our novel TIL product intrathecally in patients with glioblastoma.
CTIM-18. NRG ONCOLOGY STUDY BN007: RANDOMIZED PHASE II/III TRIAL OF IPILIMIUMAB (IPI) PLUS NIVOLUMAB (NIVO) VS. TEMOZOLOMIDE (TMZ) IN MGMT-UNMETHYLATED (UMGMT) NEWLY DIAGNOSED GLIOBLASTOMA (NGBM)
Authors: Lassman Andrew , Polly Mei-Yin , Iwamoto Fabio , Sloan Andrew , Wang Tony , Aldape Kenneth , Wefel Jeffrey , Gondi Vinai , Gutierrez Alonson , Manasawala Mohammed , Gilbert Mark , Sulman Erik , Wolchok Jedd , Green Richard , Neil Elizabeth , Lukas Rimas , Goldlust Samuel , Snuderl Matija , Dignam James , Won Minhee , Movsas Benjamin , Mehta Minesh 
Published: November 2023

Abstract

BACKGROUND
New therapies are especially needed for uMGMT nGBM. NRG Oncology BN002 (phase I) demonstrated safety and preliminary efficacy of Ipi+Nivo for nGBM, leading to BN007 as phase II/III.

METHODS
Adults with uMGMT nGBM (WHO 2016) and KPS ≥ 70 were randomized to RT and concurrent and adjuvant Ipi+Nivo or TMZ, stratified by glioma-recursive partitioning analysis class (RPA), intent to use tumor-treating fields (NCT04396860). Phase II primary endpoint was progression-free survival (PFS), powered 95% to detect a hazard ratio (HR) ≤0.58 with 1-sided 0.15 significance after 100 events. If p &lt; 0.15, then phase III would accrue with overall survival (OS) as primary endpoint. Corticosteroids were disallowed at Ipi+Nivo start. Histology, biomarkers, and PFS were assessed centrally.

RESULTS
Among 374 patients screened, 159 were randomized in phase II (79 Ipi+Nivo, 80 TMZ). Demographics (age median 60 years, range 28-79; male 66%, white 88%, not Hispanic/Latino 89%), KPS (90-100 61%), extent of resection (gross total 65% per local PI), and RPA (III 10%, IV 73%, V 17%) were well-balanced between arms. After 100 PFS events, the pre-planned phase II analysis demonstrated no improvement for Ipi+Nivo vs. TMZ [median 7.7 (95% CI: 6.5, 8.5) vs. 8.5 (95% CI: 7.1, 10.4) months; HR 1.47 (95% CI: 0.98-2.2); 1-sided p = 0.96]. OS is immature ( &gt;50% alive, 13.7 months median follow-up) but without observed difference between arms [median ~13 months each; HR 0.95 (95% CI: 0.61-1.49); 1-sided p = 0.36]. On the Ipi+Nivo arm, treatment-related grade 3, 4, and 5 events were reported in 26 (33.3%), 4 (5.1%), and 2 (2.6%; colitis and autoimmune disorder, n = 1 each) patients.

CONCLUSIONS
Ipi+Nivo did not improve PFS for uMGMT nGBM. Accrual permanently closed after phase II. No new safety signals were identified. Molecular analyses and survival follow-up are ongoing. FUNDING: NCI Grants U10CA180868, U10CA180822, U24CA196067 (NRG Oncology Operations, SDMC, Specimen Bank).
CTIM-21. T-CELL RECEPTOR REPERTOIRE ANALYSIS IN PBMCS FROM PEDIATRIC PATIENTS WITH RECURRENT MEDULLOBLASTOMA DURING ADOPTIVE CELLULAR THERAPY
Authors: Yegorov Oleg , Yang Changlin , Yegorova Yanina , Mitchell Duane 
Published: November 2023

Abstract

BACKGROUND
Adoptive cellular therapy (ACT), which involves transferring tumor-specific lymphocytes, has shown promising clinical efficacy across various cancer types. However, accurately tracking these transferred cells has been challenging. To overcome this limitation, we utilized T-cell receptor (TCR) sequencing to investigate the TCR repertoire in peripheral blood mononuclear cells (PBMCs). Specifically, we examined PBMCs stimulated ex vivo using autologous dendritic cells (DCs) loaded with total tumor RNA, which we applied for infusion in pediatric patients. We also collected blood samples prior to and following immunotherapy to compare the TCR repertoire dynamics.

METHODS
We isolated total RNA from patient PBMCs obtained before the initiation of adoptive cellular therapy (ACT) and continued collection on a weekly basis for one month, followed by monthly collections after immunotherapy treatment. To generate cDNA, we used RACE technology with the addition of a common adapter at the 5' end. The raw sequencing data obtained was then preprocessed using MiXCR software. Subsequent TCR repertoire analysis was performed using the Immunarch R-package and VDJtools software. RESULTS&

CONCLUSIONS
The analysis of T-cell receptor (TCR) diversity across ex vivo extended T-cell samples showed a range of 593 to 34,000 unique CDR3 clones among 28 patients with recurrent medulloblastoma. The observed range suggests that different patients exhibit distinct levels of TCR diversity. Our results revealed significant instability in the TCR repertoire within the peripheral blood during the initial 28 days after ACT for all patients. Subsequently, the regeneration was mainly driven by de novo thymic production of naïve T-cells. TCR sequencing of PBMCs stimulated with autologous DCs loaded with total tumor RNA allowed us to gain a deeper understanding of the TCR repertoire in the context of immunotherapy. This approach enabled us to track and analyze the tumor-specific T-cells in the repertoire, providing valuable insights into their behavior and response to the treatment.
CTIM-23. SAFETY RUN-IN RESULTS OF A PHASE I/II STUDY TO EVALUATE ATEZOLIZUMAB IN COMBINATION WITH CABOZANTINIB IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Weathers Shiao-Pei , Kamiya-Matsuoka Carlos , Majd Nazanin , Ashu Alda , Thompson Chantell , Gachimova Evguenia , Aaroe Ashley , Patel Chirag , Loghin Monica , O'Brien Barbara , Alfred Yung W K , Puduvalli Vinay , de Groot John 
Published: November 2023

Abstract

BACKGROUND
Immune checkpoint inhibitor therapy has shown limited efficacy in the treatment of glioblastoma (GBM) in both newly diagnosed and recurrent disease which underscores the need for rational combinatorial strategies. Atezolizumab is a humanized monoclonal antibody that targets PD-L1 and has been shown to enhance the magnitude of tumor-specific T cell responses. Combining PD-L1/PD-1 axis inhibition with targeted therapy like cabozantinib which has both anti-tumoral and immunomodulatory properties may result in synergistic effects. Cabozantinib may modulate the myeloid cell population to overcome resistance to anti-PD-1/PD-L1 therapy.

METHODS
Eligibility criteria were those with recurrent GBM, age &gt;18 yrs with 1st or 2nd recurrence who were naïve to antiangiogenic and receptor tyrosine kinase inhibitor treatment. The primary objective of the phase I run-in was to evaluate the safety of atezolizumab in combination with cabozantinib.

RESULTS
1 dose-limiting toxicity (DLT) of a grade 3 ALT elevation was observed in the first 6 DLT evaluable patients treated during the safety run-in phase. Regarding immune related adverse events, 1 of 6 patients developed atezolizumab-related grade 1 hypothyroidism. 1 of 6 patients developed study treatment-related grade 2 diarrhea. 2 patients after completion of 2 cycles of treatment had evidence of a partial radiographic response ( &gt; 50% decrease). 1 patient had a near partial radiographic response (45% decrease). 2 patients had stable disease after completion of 2 cycles of the combinatorial treatment. 1 patient had only completed the first 28-day cycle, DLT period, and had not yet had imaging to reassess disease status.

CONCLUSIONS
The combination of atezolizumab with cabozantinib was tolerable, and no new safety signals were noted. In this small cohort of recurrent GBM patients, radiographic responses were observed. The phase II component of the trial is recruiting patients (n = 45) to evaluate clinical efficacy. Multi-omic correlative studies and fecal microbiome analyses are planned.
CTIM-30. A PHASE 1B, OPEN-LABEL, DOSE-ESCALATION TRIAL OF THE DELTA-LIKE LIGAND 3 (DLL3)/CD3 IGG-LIKE T CELL ENGAGER, BI 764532, IN PATIENTS WITH DLL3-POSITIVE GLIOMA
Authors: van den Bent Martin , Roth Patrick , Tabatabai Ghazaleh , Burger Michael C , Martinez-Garcia Maria , von Baumgarten Louisa , Greil Richard , Studeny Matus , Simetzberger Monika , Liu Meiruo 
Published: November 2023

Abstract

BACKGROUND
Patients with progressive diffuse gliomas have limited treatment options. DLL3, a Notch ligand, is expressed on most diffuse gliomas. BI 764532, a humanized IgG-like T cell engager, binds selectively to DLL3-positive cells and promotes T cell-mediated cytotoxicity. Preclinical data showed activity of BI 764532 against intracranial tumors. In an ongoing first-in-human trial in patients with DLL3-positive small-cell lung carcinoma and other neuroendocrine carcinomas (NECs) including extrapulmonary NECs and large-cell NECs of the lung (NCT04429087), BI 764532 exhibited promising efficacy and manageable tolerability. Here we describe a planned Phase Ib dose-escalation/expansion trial of BI 764532 monotherapy in patients with DLL3-positive refractory/relapsed diffuse glioma.

METHODS
The dose-escalation part will include ~12–20 patients (≥3 patients per dose level) from 12 sites across Europe/USA. Dose escalation will be guided by Bayesian logistic regression model with overdose control. BI 764532 will be administered intravenously. Treatment will continue until disease progression, undue toxicity, informed consent withdrawn, or other reasons requiring treatment discontinuation. Once a recommended dose for expansion is established, ~15 patients from Europe will be treated in a dose-expansion phase. Key inclusion criteria: ≥18 years old; histologically confirmed primary progressive diffuse glioma who have failed on standard-of-care therapies; DLL3-positivity by IHC on archived tumor tissue by central pathology review. Key exclusion criteria: extracranial metastatic or leptomeningeal disease; previous treatment with DLL3-targeting therapies; prior treatment with bevacizumab/other anti-VEGF/anti-angiogenic treatment ≤6 months prior to first administration of BI 764532; persistent toxicity from previous treatments that has not resolved to ≤CTCAE Grade 1; diagnosis of immunodeficiency, or intake of immunosuppressive therapy ≤7 days prior to first administration of BI 764532. Primary endpoints: dose-limiting toxicities (DLTs) during the maximum tolerated dose evaluation period (escalation phase); DLTs during the entire treatment period (expansion phase). Other objectives include pharmacokinetics, pharmacodynamics, preliminary efficacy and evaluation of DLL3 as a potential biomarker.