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Chimeric antigen receptor (CAR) T-cell therapy has been shown to produce profound results in the treatment of certain hematologic malignancies, however treatment of solid tumors with CAR T cells has not been as successful. Studies have suggested that T-cell exhaustion plays a role in limiting the ability of CAR T cells to eradicate solid tumors. Additionally, stem-like qualities of T cells have been associated with better outcomes in patients treated with cellular therapies, including CAR T cells. Therefore, maintaining stem-like qualities and overcoming T-cell exhaustion may be key to improving clinical efficacy of CAR T cells in patients with solid tumors. ROR1 is a cell surface antigen expressed in several solid tumor types and chronic lymphocytic leukemia (CLL). ROR1 expression has been reported in 57% of triple-negative breast cancer (TNBC), as well as 42% of adenocarcinoma and 12% of squamous cell carcinoma subtypes of non-small cell lung cancer (NSCLC). These expression data of ROR1 in TNBC and NSCLC provide support for anti-ROR1 agents as a therapeutic strategy for these cancers. LYL797 is a novel, ROR1-targeted chimeric antigen receptor (CAR) T-cell product that incorporates genetic and epigenetic reprogramming technologies, Gen-R and Epi-R, to overcome barriers of CAR T-cell therapies in solid tumors. The ROR1-specific CAR contains a single-chain variable fragment (scFv) derived from an R12 rabbit monoclonal antibody that recognizes and binds with high specificity to human ROR1. Gen-R is ex vivo genetic reprogramming technology that engineers CAR T cells to overexpress c-Jun. Dysregulation of activator protein 1 (AP-1) has been implicated in CAR T-cell exhaustion, and studies have demonstrated that overexpression of c-Jun renders CAR T cells less susceptible to exhaustion, enhancing both anti-tumor efficacy and persistence in preclinical models of hematologic and solid tumors. Epi-R is a proprietary optimized manufacturing process that results in maintenance of stem-like phenotype and function of T-cell products. In preclinical studies LYL797 cells reprogrammed with Gen-R and Epi-R led to improved functional activity in the presence of ROR1+ tumor cells compared to conventional ROR1 CAR T cells. Additional studies are underway to determine the mechanisms by which antitumor activity of LYL797 in ROR1-positive solid tumor xenograft models is enhanced. LYL797 is anticipated to enter into Phase 1 clinical trials for TNBC and NSCLC in 2022. Citation Format: Spencer Park, Courtney Simianer, Sydney Spadinger, Xiao Wang, Purnima Sundar, Shobha Potluri, Rachel Lynn, Bijan Boldajipour, Grace Wang, Neeraj Sharma, Hajime Hiraragi, Veena Krishnamoorthy, Suman Kumar Vodnala, E-Ching Ong, Chang-Chih Wu, Martin Wohlfahrt, Byoung Ryu, Lisa Song, Brian D. Weitzner, Howell Moffett, Marc Lajoie, Scott Boyken, Tamer Shabaneh, Shivani Srivastava, Tina Albertson, Blythe Sather. LYL797, a ROR1 CAR T-cell therapy with genetic and epigenetic reprogramming for solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2754.

e20046 Background: Clinical studies of liso-cel show low incidences of severe CRS and NEs. Pts with high tumor burden and inflammation are at higher risk of CRS and NEs (Borrega, Hemasphere 2019). Here, we characterize the presenting symptoms, timing, and management of CRS and NEs in pts with R/R LBCL treated with liso-cel in TRANSCEND NHL 001 (NCT02631044). A deeper understanding of CRS/NEs after liso-cel treatment may help clinicians identify and manage these toxicities. Methods: Pts with R/R LBCL and ≥2 lines of therapy received liso-cel after lymphodepletion (LD) with fludarabine and cyclophosphamide. Bridging therapy was allowed for pts with PET-positive disease before LD (Abramson, ASH 2019 #241). Investigators were educated on prospectively identifying liso-cel–related NEs and CRS, which were collected and graded per NCI CTCAE v4.03 (NEs) or 2014 Lee criteria (CRS). Timing and severity of individual CRS/NE symptoms and interventions were also collected. Results: The analysis included 269 pts (median age, 63 y): 38% had sum of perpendicular diameters ≥50 cm2 or lactate dehydrogenase ≥500 U/L, and 59% received bridging therapy. CRS and NEs had delayed onset (median, 5 and 9 d, respectively) and a low incidence of grade (Gr) ≥3 events (CRS 2%; NE 10%). CRS occurred before NEs in most pts and was Gr 1/2 at onset in all but 2 pts (Table). The most common CRS symptoms were pyrexia (40%), hypotension (20%), and tachycardia (18%). Overall, 20% of pts received tocilizumab and/or corticosteroids for CRS (10% tocilizumab only; 2% corticosteroids only; 8% both); 3% received vasopressors. The most common NE symptoms were confusional state (11%), tremor (9%), and aphasia (8%); most were low grade. A total of 17% of pts received tocilizumab and/or corticosteroids for NEs (13% corticosteroids only; < 1% tocilizumab only; 3% both); < 1% received vasopressors. Overall, 4% of pts were admitted to the ICU for CRS and/or NEs. Additional analyses on timing of intervention and type/severity of initial symptoms will be presented. Conclusions: In pts with high-risk, aggressive R/R LBCL, liso-cel treatment was associated with a low incidence of severe CRS/NEs, late onset of mostly low-grade events at presentation, and low use of tocilizumab/corticosteroids. Clinical trial information: NCT02631044 . [Table: see text]

CD19, a member of the immunoglobulin superfamily, is a B-cell specific marker that is found on B cells as early as the pro-B cell stage. CD19 is maintained upon malignant transformation and is expressed in the majority of patients with B-lineage acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL). SGN CD19A is a novel antibody-drug conjugate (ADC) composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl (mc) linker. Upon binding to CD19, SGN-CD19A internalizes and releases cys-mcMMAF, which binds to tubulin and induces G2/M arrest and apoptosis in the targeted cells. In mice bearing B-lineage ALL and lymphoma xenografts, SGN-CD19A induced dose-dependent tumor growth delay and extended survival. Two first-in-human, phase 1, dose-escalation studies are ongoing to investigate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN CD19A; one trial in adult and pediatric patients with relapsed or refractory (R/R) B cell ALL or highly aggressive B-cell lymphoma (CT.gov NCT01786096) and the second trial in adult patients with R/R B-cell NHL (CT.gov NCT01786135). Both trials employ a modified continual reassessment method (CRM) to estimate the dose-toxicity relationship and to estimate the maximum tolerated dose. Exploratory analyses include correlation of target (CD19) expression, target saturation, and apoptotic cellular markers with clinical response and clearance of leukemic blasts; dose and PK of SGN-CD19A will also be correlated with target saturation and intracellular levels of cys-mcMMAF. Early PK analyses indicate that plasma SGN-CD19A ADC generally increases with higher doses. Rapid clearance of ADC was observed at low doses in patients with leukemia, suggesting target-mediated drug disposition. Dose escalation of SGN-CD19A is ongoing in both clinical trials. In preliminary safety analyses, SGN-CD19A was generally tolerable at doses examined to date. Encouraging antitumor activity has been observed, with multiple patients achieving complete remissions in both trials. Citation Format: Tina M. Albertson, Lali Sandalic, Baiteng Zhao, Ana Kostic, Che-Leung Law. SGN-CD19A: A novel Anti-CD19 antibody drug conjugate. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr DDT01-04. doi:10.1158/1538-7445.AM2014-DDT01-04

JCAR017 is a CD19-directed 41BB chimeric antigen receptor (CAR) T cell product administered in a defined composition at a precise dose of CD8 and CD4 CAR T cells. JCAR017 manufacturing employs process controls that enable precise independent control of the infused dose of CD8 and CD4 cells. Preliminary safety data from JCAR017 administered in relapsed/refractory B cell non-Hodgkin lymphoma (NHL) demonstrated lower rates of cytokine release syndrome (CRS) and neurotoxicity (NT) compared to those reported for other CD19-directed CAR T cell therapies with heterogeneity in total infused dose and CD8 and CD4 composition. Multiple patient factors and blood biomarkers have been identified that correlate with JCAR017 CAR T cell in vivo expansion, antitumor activity, and toxicity (Heipel M et al. and Siddiqi T et al. ASH 2017). However, little is known regarding the contribution of CAR T cell product differentiation state to pharmacokinetics (PK), clinical outcome, or toxicity. Product characterization is executed on JCAR017 to define the CAR T cell memory phenotype composition and antigen-specific function. Product attributes were assessed for relationships with clinical response, safety, and PK through univariate, multivariate, and machine learning-based analyses. JCAR017 memory T cell composition demonstrated strong relationships with cytokine production profile observed following in vitro CD19 stimulation of the CAR T cell drug product. Specifically, products with elevated frequencies of CCR7+ central memory T cells exhibited increased production of IL-2 (Spearman ρ=0.55, P Citation Format: Ryan P. Larson, Rachel Lower, Todd DeVries, Yue Jiang, Ronald J. Hause, Rich Getto, Brian Christin, Nathan K. Yee, Michael A. Bowen, Clinton Weber, Daniel Li, Tina Albertson, Claire Sutherland, Christopher G. Ramsborg. Defined cell composition and precise control over JCAR017 dose enables identification of relationships between chimeric antigen receptor T cell product attributes, pharmacokinetics, and clinical endpoints in NHL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 960.

7505Background: Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in defined composition at a precise dose of CD8 and CD4 CAR T cells. A multicen...

120 Background: JCAR017 is a defined composition, CD19-directed 4-1BB CAR T cell product administered at a precise dose of CD8 and CD4 CAR T cells in a seamless design Phase 1 pivotal trial of relapsed/refractory (R/R) B-cell NHL (TRANSCEND NHL 001; NCT02631044). Methods: Patients (pts) with R/R DLBCL NOS, PMBCL, FL grade 3B, or MCL and adequate organ function are eligible. The FULL dataset includes all pts in the DLBCL cohort (i.e. excludes MCL). The CORE dataset includes pts meeting inclusion for a planned pivotal DLBCL cohort (DLBCL NOS [ de novo or transformed from follicular lymphoma], ECOG 0-1, no prior allo-SCT). Results: As of July 7, 2017, 69 pts were treated in the DLBCL cohort and evaluable for safety. In the FULL dataset, 21 pts (30%) had cytokine release syndrome (CRS), with 1 serious CRS event (1%; Gr 4). Neurotoxicity (NT) at any grade developed in 14 (20%), including 10 (14%) with Gr 3-4 events. There were no Gr 5 CRS or NT events. Median time to onset of first CRS and NT was 5 days and 10 days, respectively, 13 (19%) received anti-cytokine therapy and only one required vasopressor support. In the CORE dataset (n = 49), similar rates of CRS and NT were shown. The majority of pts, 64% (44/69), had no CRS or NT, and median onset of CRS and NT were 5 and 11 days, respectively, suggesting outpatient delivery of JCAR017 may be feasible. In the DLBCL cohort, 68 pts were evaluable for efficacy; best overall response, 3-month, and 6-month response rates in the FULL dataset were 75% (51/68), 49% (27/55), and 40% (14/35), respectively; and, in the CORE dataset, were 84% (41/49), 65% (26/40), and 57% (13/23). The best overall, 3-month, and 6-month CR rates were 61% (30/49), 53% (21/40), and 52% (12/23), respectively, in the CORE dataset. Among 16 double/triple hit pts, best ORR was 81%, and 3-month CR rate was 60%. A trend toward improved response rate at 3 months was observed in pts treated at DL2 compared to DL1. Conclusions: At the symposium, we will report updated efficacy and the preliminary safety profile for JCAR017, which supports potential outpatient administration in R/R Aggressive B-NHL patients. Clinical trial information: NCT02631044.

7513 Background: JCAR017 is a second-generation, CD19-directed, 4-1BB CAR T cell product comprising CD8 and CD4 CAR T cells in a 1:1 ratio. A multicenter phase 1 trial of JCAR017 in R/R B-cell NHL (NCT02631044) is underway. Methods: Patients with R/R DLBCL, PMBCL, FL grade 3B, or MCL and adequate organ function are eligible. There was no minimum ALC requirement for apheresis; no test expansion was required. Treatment includes lymphodepletion with fludarabine and cyclophosphamide, followed by JCAR017. Multiple dose levels (DLs)/administration schedules of JCAR017 are being evaluated. Study objectives include safety, PK, and antitumor response. Results: As of November 23, 2016, 28 patients have been treated and are evaluable for safety and efficacy. Nineteen were male, 9 female; 25 DLBCL, 2 MCL, and 1 FL grade 3B. Median age was 63 years (range 37-79), median number of prior therapies was 4 (range 1-8), 23 (82%) were refractory to their last chemotherapy, and 16 (57%) had prior transplant. No severe cytokine release syndrome (sCRS) was observed; 10 patients had grade 1-2 CRS (1 received tocilizumab). Five patients developed neurotoxicity, including 4 grade 3-4; all events resolved in the 4 patients who had adequate follow up. Median onset of CRS and neurotoxicity were 5 and 11 days, respectively. Four deaths after disease progression occurred, none related to JCAR017. In 20 patients treated at DL1 (5×107 cells), the RR was 80% with 60% achieving CR. One patient with secondary CNS involvement achieved CR without neurotoxicity. JCAR017 was detected at 3 and 6 months in responding patients, including some who relapsed; higher mean peak levels were detected in patients with durable response at 3 months. Data on patients treated at DL2 (1×108 cells), alternative dose schedules, tumor biopsy, and additional biomarkers will be presented. Conclusions: Treatment with JCAR017 results in high CR rate in patients with heavily pretreated R/R DLBCL. Relapses can occur despite persistence of JCAR017, suggesting tumor immune evasion mechanisms may contribute to relapse. Observed toxicities are manageable and occurred at rates lower than those reported for other CD19-directed CAR T cell products. Clinical trial information: NCT02631044.

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA SGN-CD19A is an antibody drug conjugate (ADC) that recognizes CD19, a B-cell specific marker expressed in B-cell malignancies including non-Hodgkin lymphoma (NHL). SGN-CD19A is currently in a phase I clinical trial for adult patients with relapsed refractory B-cell NHL (CT.gov [NCT01786135][1]) in which it has shown evidence of single-agent activity (1). This ADC binds CD19, internalizes, and releases cys-mcMMAF, which ultimately induces apoptosis in targeted cells (2). Lymphoma tumor xenografts treated with SGN-CD19A show growth delay in a dose dependent manner. Here we show that SGN-CD19A in combination with standard of care [rituximab/ifosfamide/carboplatin/etoposide (R-ICE), rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP), or components] exceeds the activity of SGN-CD19A alone and results in impressive anti-tumor activity in multiple xenograft models. It was notable that in some xenograft models, SGN-CD19A + R-CHOP or SGN-CD19A + R-ICE yielded activity that was similar to SGN-CD19A plus rituximab alone. This strong interaction between rituximab and SGN-CD19A was modeled in vitro. SGN-CD19A synergized with rituximab, in the absence of cross-linking, to cause decreased cell viability in NHL cell lines. These data suggest that cell autonomous signaling contributes to the unique interaction between rituximab and SGN-CD19A. Our in vivo and in vitro data support R-CHOP, R-ICE, or rituximab as viable combination therapies for NHL patients with SGN-CD19A. 1) Uma Borate et al. A first-in-human phase 1 study of the antibody-drug conjugate SGN-CD19A in relapsed or refractory B-lineage acute leukemia and highly aggressive lymphoma. Blood 2013 122:1437 2) Che-Leung Law et al. Preclinical characterization of an auristatin-based anti-CD19 drug conjugate, SGN-19A. Abstract number 625. In: Proceedings of the 102th Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Citation Format: Heather A. Van Epps, Kerry Klussman, Martha Anderson, Weiping Zeng, Devra Olson, Maureen Ryan, Tina Albertson, Che-Leung Law. Preclinical results of SGN-CD19A in combination with R-ICE or R-CHOP in non-Hodgkin lymphoma models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2541. doi:10.1158/1538-7445.AM2015-2541 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01786135&atom=%2Fcanres%2F75%2F15_Supplement%2F2541.atom

Introduction: Positron emission tomography (PET) imaging is a non-invasive tool to quantitatively describe the drug distribution in vivo. To answer the question whether radiolabeled antibody-drug conjugates (ADCs) can be utilized as PET imaging probes, and to explore PET imaging sensitivity for detecting antigen expression, we conducted preclinical microPET/CT imaging studies with radiolabeled SGN-35 in SCID mice bearing tumors with varying levels of CD30 expression. Methods: SGN-35 was either directly labeled with 124Iodine or conjugated with the chelator desferrioxamine (DFO) and subsequently labeled with 89Zirconium. Karpas 299, TF1-α, and Daudi were selected as the representative high (CD30high), low (CD30low) and negative (CD30neg) CD30 expressing tumor cell lines, respectively. Expression of CD30 and receptor copy number on each cell line was confirmed by quantitative FACS assay. One mouse from each CD30 expression group was administered a single IV bolus dose of either 124I-SGN-35 (0.5 mg/kg) or 89Zr-Df-SGN-35 (1 mg/kg), and serially imaged 0 - 2 hours (dynamic scan), and at 4, 24, 48, 72, 96 and 144 hours (10 min static scans). An additional 3 mice with CD30high and CD30low tumors, and 2 mice with CD30neg tumors, were dosed and imaged at 72, 96 and 144 hours (10 min static scans). Blood samples (10 μL) were taken from mice at 0, 4, 24, 48, 72, 96 hours and by cardiac puncture at 144 hours for pharmacokinetic (PK) analysis. Additional mice (n=4 per group) were sacrificed at 72 and 144 hours to determine tissue biodistribution via gamma counting. Results: The elimination of 124I-SGN-35 and 89Zr-Df-SGN-35 followed 2-compartment PK, and the calculated elimination T1/2 was 3.6-3.9 days. In mice bearing CD30high tumors with ∼291,000 CD30 copies per cell, the tumor:blood ratio of 124I-radioactivity after a dose of 124I-SGN-35 fell from 1.24 after 72 hours to 0.78 after 144 hours, whereas after a dose of 89Zr-Df-SGN-35, mean tumor:blood ratio of 89Zr-radioactivity increased from 7.38 at 72 hours to 15.05 (157.5 %ID/g) at 144 hours. The 124I-radioactivity and 89Zr-radioactivity tumor:blood ratio in the CD30neg tumors was 0.2 and 0.5 after 144 hours, respectively. The tumor:blood ratio of 89Zr-radioactivity continued to increase from 0.57 after 72 hours to 0.90 (13.4 %ID/g) at 144 hours after a dose of 89Zr-Df-SGN-35 in TF1-α (CD30low) tumor bearing mice. Conclusions: These results indicate that 89Zr-Df-SGN-35 retains the specific anti-CD30 immune-reactivity and PK of the parent SGN-35 molecule. 89Zr labeling generated superior imaging results compared with 124I labeling. With respect to specificity, a favorable tumor:blood ratio was observed in the CD30high tumor bearing mice in contrast to the lack of accumulation of 89Zr-radioactivity in the CD30 negative tumors. The accumulation of 89Zr-radioactivity in CD30low TF1-α tumors suggests that 89Zr-Df-SGN-35 is a very sensitive CD30 targeted PET/CT imaging agent. Citation Format: Aaron Moss, Jean Gudas, Tina Albertson, Nancy Whiting, Che-Leung Law. Preclinical microPET/CT imaging of 89Zr-Df-SGN-35 in mice bearing xenografted CD30 expressing and non-expressing tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 104. doi:10.1158/1538-7445.AM2014-104

8505 Background: CD19, a member of the immunoglobulin superfamily, is expressed in most patients with B-cell NHL. SGN-CD19A is a novel antibody-drug conjugate composed of a humanized anti-CD19 mono...

Background. CD19 is a member of the immunoglobulin superfamily that regulates B-lineage cell development and differentiation. It is not known to be expressed by any cell outside of the B-lineage and expression is maintained upon malignant transformation. Due to its restricted normal tissue expression profile, CD19 is an attractive target for antibody-based therapeutics for the treatment of B-lineage malignancies. SGN-CD19A is a novel antibody-drug conjugate composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl (mc) linker. Upon binding to CD19, SGN-CD19A internalizes and releases cys-mcMMAF, which binds to tubulin and induces G2/M arrest and apoptosis in the targeted cells. We describe two first-in-human, dose-escalation studies of SGN-CD19A. Methods. The objectives of both studies include evaluation of safety, tolerability, the pharmacokinetic (PK) profile, and antitumor activity of SGN-CD19A in patients with relapsed or refractory B-lineage malignancies. SGN19A-001 will evaluate a weekly (days 1 and 8 of 21-day cycles) and an every 3 week (q3wk) IV dosing schedule in adult and pediatric patient populations with B-lineage acute lymphoblastic leukemia and aggressive lymphoma. SGN19A-002 will enroll adult patients with B-lineage non-Hodgkin lymphoma and will test a q3wk IV dosing schedule. Both trials will employ a modified continual reassessment method (CRM) to estimate the dose-toxicity relationship, estimate the maximum tolerated dose (MTD), and allocate patients to dose levels. Each trial has an additional dose-finding expansion phase that can be initiated to further evaluate multiple doses and schedules to help identify a recommended phase 2 dose based on a utility score that weighs both toxicity and efficacy in different patient populations. The CRM algorithm estimates the efficacy and toxicity of each patient population and disease subgroup by borrowing information across groups (age and disease). Exploratory analyses will include correlation of target (CD19) expression, target saturation, and apoptotic cellular markers with clinical response and clearance of leukemic blasts; dose and PK of SGN-CD19A will also be correlated with target saturation and intracellular levels of cys-mcMMAF. These studies are scheduled to be initiated by late 2012. Expected Results. The CRM design will allow the MTDs to be identified with high probability. As designed, we expect 10 pediatric and/or 20 adult patients to be treated at or around the estimated MTDs during dose escalation. During the dose-finding expansion portions, refined estimates of the MTDs and estimates of antitumor activity at multiple dose levels will provide rationale for the best dosing regimen for future phase 2 trials. Citation Format: Tina M. Albertson, Lali Sandalic, Che-Leung Law, Kristine Broglio, Scott Berry. Phase 1, open-label, dose-escalation studies of SGN-CD19A in patients with relapsed or refractory B-lineage acute leukemia and non-Hodgkin lymphoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2412. doi:10.1158/1538-7445.AM2013-2412

3069 Background: CD30 is commonly expressed in Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL), and testicular embryonal carcinoma. Expression of CD30 in other solid tumors and non-lymphomatous malignancies has been reported but not investigated systematically. CD30 is the target of brentuximab vedotin (Adcetris), an antibody drug conjugate (ADC) that is approved for the treatment of patients with relapsed HL and systemic ALCL after failure of other therapies. A study was initiated to determine the incidence of CD30 expression in non-lymphomatous malignancies and to identify patients who may be candidates for treatment with brentuximab vedotin. Methods: Patients with non-lymphomatous malignancies were eligible for screening if they were relapsed or refractory to previous therapy or had no effective treatment options available. Archived tissue from solid tumors was tested for CD30 expression by immunohistochemistry (IHC); fresh bone marrow or blood samples from multiple myeloma or leukemia patients were tested by flow cytometry. Patients were considered CD30 positive and eligible for a companion treatment protocol with brentuximab vedotin if ≥10% of malignant cells stained positive by IHC or ≥20% by flow cytometry. Results: At this interim analysis, a total of 875 patients have been tested for CD30 expression: 95% had solid tumors, 3% had leukemia, and 2% had multiple myeloma. Twenty-two patients (2.5%) were CD30 positive, including 7 of 94 patients with ovarian cancer (7%), 5 of 20 with melanoma (25%), 2 of 5 with mesothelioma (40%), 1 of 4 with skin squamous cell carcinoma (25%), 2 of 41 with triple negative breast cancer (5%), 1 of 37 with pancreatic cancer (3%), 1 of 26 with small cell lung cancer (4%), and 1 of 3 with anal cancer (33%), and thyroid carcinoma (33%). One patient was identified with CD30-positive mast cell leukemia. In positive patients, the percent of CD30-positive malignant cells varied between 10 and 80%. Conclusions: CD30 expression was observed in multiple types of non-lymphomatous malignancies, thereby identifying additional populations who may be candidates for treatment with a CD30-targeted ADC, such as brentuximab vedotin. A companion clinical trial with brentuximab vedotin is currently ongoing.