Updated safety and efficacy of MSB2311 (an anti-programmed death-ligand 1 antibody) in Chinese patients with advanced solid tumors and hematological malignancies from a phase 1 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14547-e14547
Author(s):  
Lin Shen ◽  
Jifang Gong ◽  
Jian Zhang ◽  
Dongmei Ji ◽  
Haijun Zhong ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Solid Tumor ◽  
Phase 1 ◽  
Chinese Patients ◽  
Binding Property ◽  
Advanced Solid Tumors ◽  
Tumor Patients ◽  
Durable Response ◽  
Programmed Death ◽  
Grade 3

e14547 Background: MSB2311 is a novel humanized PD-L1 antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration. Methods: Patients with metastatic solid tumors or selected lymphoma progressed on or after standard treatments were enrolled in this phase I study. In dose escalation part, MSB2311 was given at dose levels of 3, 10, and 20 mg/kg intravenously every 3 weeks. At the dose expansion part, patients with enriched biomarker expression, including EBV+, PD-L1+ (TPS≥50%), MSI-High or TMB-High (≥10muts/Mb), were dosed at 20mg/kg Q3W or 10mg/kg Q2W. Primary objectives are to evaluate the safety and tolerability and to identify MTD and RP2D. Secondary objectives include the assessment of pharmacokinetic parameter, immunogenicity, and preliminary anti-cancer activity per RECIST1.1. Results: As of data cutoff by Aug 31, 2020, 33 Chinese patients had been treated, including 27 heavily pre-treated solid tumor patients and 6 lymphoma patients. No dose limiting toxicity was reported and MTD has not been reached. The most common AEs (>20%) included: anemia, hypothyroidism, aspartate aminotransferase elevated, proteinuria, weight loss. 13 patients (39.4%) experienced grade 3 AEs, and 6 patients (18.2%) experienced SAEs. No treatment related grade 4 or 5 event was reported. Of the 17 efficacy evaluable solid tumor patients with biomarker selection, 6 achieved confirmed partial response with 35% ORR: 2/8 (25%) at 10 mg/kg Q2W and 4/9 (44%) at 20 mg/kg Q3W. Additionally, one patient achieved sustained iPR via iRECIST. 4 out of 7 responding patients (including one iPR) achieved tumor shrinkage of more than 50%, 3 of them got durable response (≥24 weeks).1 out of 6 lymphoma patients achieved PR. Conclusions: MSB2311 demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors and selected lymphomas. Clinical trial information: NCT04272944.

MSB2311, an anti-programmed death-ligand 1 antibody, in advanced solid tumors and hematological malignancies: Safety and tolerability, early anti-cancer activities from a phase I study in Chinese patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15011-e15011
Author(s):  
Xichun Hu ◽  
Jifang Gong ◽  
Dongmei Ji ◽  
Lin Shen ◽  
Yufeng Li ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Phase I Study ◽  
Hematological Malignancies ◽  
Chinese Patients ◽  
Binding Property ◽  
Advanced Solid Tumors ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Experienced Grade

e15011 Background: MSB2311 is a novel humanized programmed death-ligand 1 (PD-L1) antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration. Methods: Patients with metastatic solid tumors and selected hematological malignancies progressed after standard treatments were enrolled in this Phase I study. In dose escalation part, MSB2311 was given at levels of 3, 10, and 20 mg/kg intravenously every 3 weeks. At the dose expansion part, patients with enriched biomarker expression, either EBV positive, PD-L1 positive, MSI-High or TMB-High, were enrolled and dosed either in 20mg/kg Q3W or 10mg/kg Q2W. Primary objectives are to evaluate the safety and tolerability and to identify MTD/MAD and RP2D. Secondary objectives include the assessment of pharmacokinetics, immunogenicity, and preliminary efficacy per RECIST1.1. Results: At data cut-off at Jan 19, 2020, 27 Chinese patients have been treated, 18 (66.7%) of them received at least 4 cycles of MSB2311. No dose limiting toxicity was reported and MTD has not been identified. The most common treatment-emergent adverse events (TEAEs) ( > 10%) included: anemia, hypothyroidism, hyperglycemia, hypertriglyceridemia, nausea, vomiting, fatigue, malaise, pyrexia and cough. Eleven patients (40.7%) experienced Grade 3 TEAEs, and 6 patients (22.2%) experienced SAEs. One lymphoma patient experienced grade 4 hypercalcemia and platelet count decreased, which were assessed as related to study drug by the investigator. MSB2311 displayed a linear pharmacokinetic profile with calculated T1/2 of about 10-13 days. Among 18 evaluable patients treated with 20 mg/kg Q3W, the best response of PR was observed in 4 out of 12 patients with solid tumors including NSCLC, NPC and Gastric cancer, and 1 out of 6 patients with lymphoma. The mean duration of response was 127 (range 38-278) days. Conclusions: MSB2311 demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors and hematological malignancies.

scholarly journals Safety and clinical activity of intratumoral MEDI9197 alone and in combination with durvalumab and/or palliative radiation therapy in patients with advanced solid tumors

2020 ◽  
Vol 8 (2) ◽  
pp. e001095 ◽  
Author(s):  
Lillian Siu ◽  
Joshua Brody ◽  
Shilpa Gupta ◽  
Aurélien Marabelle ◽  
Antonio Jimeno ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Solid Tumors ◽  
Phase 1 ◽  
Objective Response ◽  
Clinical Activity ◽  
Advanced Solid Tumors ◽  
Palliative Radiation ◽  
Cell Counts ◽  
Palliative Radiation Therapy ◽  
Grade 3

BackgroundMEDI9197 is an intratumorally administered toll-like receptor 7 and 8 agonist. In mice, MEDI9197 modulated antitumor immune responses, inhibited tumor growth and increased survival. This first-time-in-human, phase 1 study evaluated MEDI9197 with or without the programmed cell death ligand-1 (PD-L1) inhibitor durvalumab and/or palliative radiation therapy (RT) for advanced solid tumors.Patients and methodsEligible patients had at least one cutaneous, subcutaneous, or deep-seated lesion suitable for intratumoral (IT) injection. Dose escalation used a standard 3+3 design. Patients received IT MEDI9197 0.005–0.055 mg with or without RT (part 1), or IT MEDI9197 0.005 or 0.012 mg plus durvalumab 1500 mg intravenous with or without RT (part 3), in 4-week cycles. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics, pharmacodynamics, and objective response based on Response Evaluation Criteria for Solid Tumors version 1.1. Exploratory endpoints included tumor and peripheral biomarkers that correlate with biological activity or predict response.ResultsFrom November 2015 to March 2018, part 1 enrolled 35 patients and part 3 enrolled 17 patients; five in part 1 and 2 in part 3 received RT. The maximum tolerated dose of MEDI9197 monotherapy was 0.037 mg, with dose-limiting toxicity (DLT) of cytokine release syndrome in two patients (one grade 3, one grade 4) and 0.012 mg in combination with durvalumab 1500 mg with DLT of MEDI9197-related hemorrhagic shock in one patient (grade 5) following liver metastasis rupture after two cycles of MEDI9197. Across parts 1 and 3, the most frequent MEDI9197-related adverse events (AEs) of any grade were fever (56%), fatigue (31%), and nausea (21%). The most frequent MEDI9197-related grade ≥3 events were decreased lymphocytes (15%), neutrophils (10%), and white cell counts (10%). MEDI9197 increased tumoral CD8+ and PD-L1+ cells, inducing type 1 and 2 interferons and Th1 response. There were no objective clinical responses; 10 patients in part 1 and 3 patients in part 3 had stable disease ≥8 weeks.ConclusionIT MEDI9197 was feasible for subcutaneous/cutaneous lesions but AEs precluded its use in deep-seated lesions. Although no patients responded, MEDI9197 induced systemic and intratumoral immune activation, indicating potential value in combination regimens in other patient populations.Trial registration numberNCT02556463.

scholarly journals Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000437
Author(s):  
Lin Shen ◽  
Jun Guo ◽  
Qingyuan Zhang ◽  
Hongming Pan ◽  
Ying Yuan ◽  
...  
Keyword(s):  
Cell Death ◽  
Antitumor Activity ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Phase 1 ◽  
Chinese Patients ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Dose Verification ◽  
Open Label

BackgroundTislelizumab is an investigational, humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death-1 (PD-1) that was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy.MethodsThe purpose of this phase 1/2, open-label, non-comparative study was to examine the safety, tolerability, and antitumor activity of tislelizumab in adult (≥18 years) Chinese patients with histologically or cytologically confirmed advanced solid tumors with measurable disease. The phase 1 portion of the study consisted of a dose-verification study and a pharmacokinetic (PK) substudy; phase 2 was an indication-expansion study including 11 solid tumor cohorts. Patients previously treated with therapies targeting PD-1 or its ligand, programmed cell death ligand-1 were excluded. During dose-verification, dose-limiting toxicities (DLTs) were monitored; safety and tolerability were examined and the previously determined recommended phase 2 dose (RP2D) was verified. The primary endpoint of phase 2 was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors V.1.1.ResultsAs of December 1, 2018, 300 patients were treated with tislelizumab 200 mg intravenously once every 3 weeks (Q3W). Median duration of follow-up was 8.1 months (range 0.2–21.9). No DLTs were reported during the phase 1 dose-verification study and the RP2D was confirmed to be 200 mg intravenously Q3W. Most treatment-related adverse events (62%) were grade 1 or 2, with the most common being anemia (n=70; 23%) and increased aspartate aminotransferase (n=67; 22%). Of the 251 efficacy evaluable patients, 45 (18%) achieved a confirmed clinical response, including one patient from the PK substudy who achieved a complete response. Median duration of response was not reached for all except the nasopharyngeal carcinoma cohort (8.3 months). Antitumor responses were observed in multiple tumor types.ConclusionsTislelizumab was generally well tolerated among Chinese patients. Antitumor activity was observed in patients with multiple solid tumors.Trial registration numberCTR20160872.

Phase I trial of chloroquine (CQ)/hydroxychloroquine (HCQ) in combination with carboplatin-gemcitabine (CG) in patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3027-3027 ◽  
Author(s):  
Nagla Fawzy Abdel Karim ◽  
Imran Ahmad ◽  
Ola Gaber ◽  
Ihab Eldessouki ◽  
Olugbenga Olanrele Olowokure ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Early Stage ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Late Phase ◽  
Survival Rates ◽  
Maximum Tolerated Dose ◽  
Advanced Solid Tumors ◽  
Dose Escalation Study ◽  
Grade 3

3027 Background: Autophagy is a catabolic process triggered in cells during periods of stress to enable their survival. Established tumors utilize autophagy to survive periods of metabolic or hypoxic stress. Inhibition of early stage autophagy can rescue cancer cells, while inhibition of late stage autophagy will lead to cell death due to accumulation of damaged organelles. The antimalarial drugs CQ and HCQ inhibit late phase autophagy. The goal of our study is to assess the safety, tolerability and activity of combining CQ/HCQ with CG in advanced solid tumor patients who either progressed on other therapies or in whom CG is a therapeutic option. Methods: This single institution phase 1 dose-escalation study was designed to evaluate the maximum tolerated dose (MTD) of CQ, later substituted with HCQ, in combination with CG in patients with previously treated advanced solid tumors. Secondary objectives were to determine ORR, PFS and OS. A starting dose of 50 mg of CQ/HCQ was used in conjunction with CG, and increased in increments of 50 mg in each dose cohort. Grade 3 or greater toxicity that is treatment-related, and was not self-limited, or controlled in less than 7 days was considered dose limiting toxicity (DLT). Results: Twenty-three patients were enrolled with a median follow up of 6 months. HCQ 100 mg was found to be the MTD in combination with CG with ≥Grade 3 thrombocytopenia and/or neutropenia as dose-limiting. Median OS was 11 months, and the 1- and 3- year overall survival rates were 30% and 7%, respectively. Median progression free survival was 5 months and the 6-, 12-, and 18-months progression-free survivals were 48%, 21% and 14%, respectively (Table). Conclusions: The MTD identified for CQ/HCQ was lower than previously reported with concomitant use of chemotherapeutic regimes, likely due to the myelosuppressive nature of CG. Clinical trial information: NCT02071537. [Table: see text]

scholarly journals Surufatinib Plus Toripalimab in Patients with Advanced Solid Tumors: A Single-Arm, Open-Label, Phase 1 Trial

2020 ◽  
Author(s):  
Yanshuo Cao ◽  
Ming Lu ◽  
Yu Sun ◽  
Jifang Gong ◽  
Jie Li ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Phase 1 Trial ◽  
Open Label Phase ◽  
Grade 3

Abstract BackgroundPreclinical studies have supported a potential synergistic antitumor activity between surufatinib and anti-programed death ligand-1 (PD-L1). We describe here the results of a single-arm, open-label phase 1 trial to evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) in patients with advanced solid tumors treated with surufatinib combined with toripalimab, an inhibitor of PD-L1.MethodsThis is an open-label, dose escalation and expansion study in patients with solid tumors who had failed standard therapies or had no effective treatment. In the dose escalation stage, 3 cohorts of patients were treated with surufatinib, at dose levels of 200, 250, or 300 mg once daily (QD) in combination with a fixed dose of toripalimab 240 mg, every 3 weeks (Q3W), to evaluate maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Additional patients were enrolled in the dose expansion phase to further assess the efficacy, safety, and PK profile.ResultsFrom April 1, 2019 to July 10, 2020, 31 patients were screened, of which 28 patients were enrolled. One patient in the 300 mg cohort experienced dose limited toxicity (DLT), a grade 3 hyperthyroidism. The top 3 most common treatment-related adverse events of ≥ grade 3 were transaminases increased (17.9%), hypertension (14.3%) and blood bilirubin increased (10.7%). No treatment-related death or treatment discontinuation was identified. The RP2D was determined to be surufatinib 250 mg QD plus toripalimab 240 mg Q3W. Overall objective response rate was 22.2% [95% confidential interval (CI) 8.6‒42.3], and disease control rate reached 81.5% (95% CI 61.9‒93.7). ConclusionsSurufatinib plus toripalimab was well-tolerated, with no unexpected safety signals, and showed promising antitumor activity in patients with advanced solid tumors. Trial registrationclinicaltrials.gov, NCT03879057; Registered March 18, 2019, https://clinicaltrials.gov/ct2/show/NCT03879057

SWOG S1221: A phase 1 dose escalation study co-targeting MAPK-dependent and MAPK-independent BRAF inhibitor resistance in BRAF mutant advanced solid tumors with dabrafenib, trametinib, and GSK2141795 (ClinicalTrials.gov NCT01902173).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2578-2578 ◽  
Author(s):  
Alain Patrick Algazi ◽  
James Moon ◽  
Bartosz Chmielowski ◽  
Roger Lo ◽  
Kari Lynn Kendra ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Braf V600e ◽  
Advanced Solid Tumors ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Braf Mutant

2578 Background: Aberrant PI3K/AKT signaling in BRAF mutant cancers contributes to resistance to MAPK pathway blockade. We conducted parallel phase 1 dose escalation studies of the doublet of the BRAFi dabrafenib with the AKT inhibitor GSK2141795 and of the triplet of dabrafenib, the MEKi trametinib, and GSK2141795. Methods: Patients (pts) with BRAF-V600E/K mutant advanced solid tumors with adequate end-organ function were eligible regardless of prior BRAFi and MEKi exposure. All pts received dabrafenib at 150 mg twice daily (bid), in the doublet cohorts together with dose escalation (3 + 3 scheme) of GSK2141795 started at 50 mg daily (qd), and in the triplet cohorts with dose escalation of both trametinib starting at 1.5 mg qd and GSK2141795 starting at 25 mg qd. DLTs included significant grade 3 and 4 adverse events (CTCAE v4) within the first 56 days of treatment. Radiographic responses were assessed at 8-week intervals. Results: No DLTs were observed in the doublet cohorts (N = 8) up to dabrafenib 150 mg bid and GSK2141795 75 mg qd. In the triplet cohorts (N = 11), no DLTs were observed at doses of up to trametinib 1.5 mg daily with GSK2141795 75 mg daily. At the highest triplet dose with dabrafenib 150 mg bid, trametinib 2 mg qd with GSK2141795 75 mg qd, 1 of 2 evaluable pts had a DLT of grade 3 febrile neutropenia and grade 3 maculo-papular rash. 2/2 treatment-naïve in the doublet cohorts had PRs (1 melanoma and 1 thyroid) the latter lasting over 1 year. 1/6 BRAF inhibitor-refractory (melanoma) pts also had an objective response. In the triplet cohorts, 3 of 6 treatment-naïve pts had a PR (1 melanoma, 2 lung). One lung pt remains in PR at 2 months and the otherhas an uPR at 1.2 months. Conclusions: Inhibition of both MAPK and PI3K/AKT pathways was well tolerated, leading to durable objective responses in pts with metastatic melanoma, thyroid cancer, and lung cancer. Further study of dual pathway inhibition is warranted. Funding: Supported in part by NIH/NCI grants CA180888, CA180819; and in part by Novartis Pharmaceuticals Corporation and GlaxoSmithKline, LLC. Clinical trial information: NCT01902173.

A phase I, open-label, nonrandomized, pharmacokinetic study of trifluridine/tipiracil (TAS-102) in Chinese patients with solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14079-e14079
Author(s):  
Xicheng Wang ◽  
Jianfeng Zhou ◽  
Yan Li ◽  
Yuping Ge ◽  
Yanping Zhou ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase 1 ◽  
Chinese Patients ◽  
Open Label ◽  
Significant Difference ◽  
Inactive Metabolite ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Experienced Grade ◽  
Clinical Trial Information

e14079 Background: Trifluridine/tipiracil (TAS-102) is an oral combination of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and the thymidine phosphorylase inhibitor, tipiracil (TPI). Trifluridine/tipiracil is demonstrated as a valid treatment choice for Asian and Western patients (pts) with metastatic colorectal cancer refractory or intolerant to standard chemotherapies in earlier studies. Its pharmacokinetic (PK) profile was also investigated in American and Japanese phase 1 studies, but never in Chinese pts. This study was conducted to investigate the PK profile of Trifluridine/tipiracil in a Chinese population with solid tumors. Methods: Pts who has responded poorly to existing standard treatment received Trifluridine/tipiracil (35 mg/m2/dose), orally BID, on days 1-5 and days 8-12 every 4 weeks until one of discontinuation criteria was met. Blood samples for PK analysis of FTD (the active compound), fluorothymine (FTY, inactive metabolite) and TPI were collected after single and multiple doses of Trifluridine/tipiracil on days 1 and 12 of cycle 1. The safety, tolerability, and antitumor activity of Trifluridine/tipiracil were also assessed as secondary endpoints. Results: A total of 15 pts were administered Trifluridine/tipiracil and analyzed for PKs. The PKs of FTD, FTY, and TPI in Chinese pts were comparable to those in Japanese pts. Compared with American pts, although the AUC0-t of TPI on day 12 was significantly lower in Chinese pts, the Cmax and AUC0-t of FTD were not significantly different. Thirteen (86.7%) pts reported treatment-emergent adverse events (TEAEs), and eight (53.3%) pts experienced grade 3 TEAEs, of which anemia and fatigue were most frequently (≥10% of patients) reported. Grade 4 or 5 TEAEs were not observed. Conclusions: The PKs of Trifluridine/tipiracil in Chinese pts were comparable to those in Japanese pts. The exposure of FTD was showed without significant difference between Chinese, Japanese and American pts. Trifluridine/tipiracil was well-tolerated in Chinese pts and had the similar safety profile in comparison with previous studies. Clinical trial information: NCT02261532.

Evolving development of PD-1 therapy: Cetrelimab (JNJ-63723283) from monotherapy to combination with erdafitinib.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3055-3055
Author(s):  
Victor Moreno ◽  
Yohann Loriot ◽  
Piotr Rutkowski ◽  
Carmen Beato ◽  
Enriqueta Felip ◽  
...  
Keyword(s):  
Solid Tumors ◽  
San Francisco ◽  
Phase 1 ◽  
Response Rates ◽  
Nonsmall Cell Lung Cancer ◽  
Complete Response ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Duration Of Treatment ◽  
Grade 3

3055 Background: Cetrelimab (CET) is an investigational checkpoint inhibitor (CI). In part 1 of a first-in-human (FIH) trial (LUC1001; NCT02908906), pts with advanced solid tumors with ≥1 prior treatment received CET 80–800 mg Q2W or 480 mg Q4W. Response rates and safety profiles were similar to other CIs. Based on preclinical and clinical data, a phase 1/2 study (NORSE; NCT03473743) of CET + erdafitinib (ERD) in metastatic urothelial carcinoma (mUC) + FGFR alterations (alt) was initiated and is ongoing. Methods: In LUC1001 Part 2, pts with nonsmall cell lung cancer (NSCLC), melanoma (MEL), or MSI-H/dMMR colorectal cancer (CRC) received CET IV 240 q2w. Overall response rates (ORR = % complete response + partial response [PR] confirmed) were assessed as per RECIST v1.1. Adverse events (AEs) were assessed for all patients receiving CET IV 240 q2w in parts 1 and 2. Results: As of July 1, 2019, 122 pts with NSCLC (n=30); MEL (n=50); or CRC (n= 42) had been treated in Part 2. Median age ranged from 58 to 64 yrs (overall range, 23–86 yrs). Duration of treatment was 8.1 mos (range, 0.0-24.7) for NSCLC; 5.5 mos (range, 0.0-25.0) for MEL; and for 3.0 mos (0.0-16.1) for CRC. ORR was 37% in NSCLC; 53% in PD-L1+ NSCLC (≥50% by IHC), 28% in MEL; 32% in non-uveal MEL, 14% in CRC and 24% in centrally confirmed MSI-high CRC. In all CET IV 240 q2w treated pts in the FIH study (N= 162), treatment-related grade ≥3 and serious AEs were reported in 15% and 12% of pts, respectively. All grade and grade ≥3 immune-related (ir) AEs were reported in 41% and 8% of pts, respectively Most common ir AE: hypothyroidism (8%), asthenia (6%), diarrhea (4%), rash (4%), hyperthyroidism (4%), dyspnea (3%), pruritis (3%) and pneumonitis (3%). There was 1 treatment-related death due to myasthenia gravis. In the phase 1 combination study (NORSE), pts with mUC + FGFR alt (n=17) received fixed-dose CET IV 240 q2w + ERD 6mg, 8 mg or 8mg + up titration (UpT) to 9 mg to establish the RP2D for the combination as CET + ERD 8mg + UpT. In the RP2D group (n=10), 60% had treatment-related grade ≥3 AEs. ORR (all confirmed PR) was 50% in the all treated response-evaluable group (n=16). Conclusions: CET is a CI with efficacy and safety profiles in advanced solid tumors similar to approved CIs. In NORSE phase 1, CET+ ERD demonstrated antitumor activity in mUC with an acceptable safety profile. NORSE phase 2 is evaluating this combination as first-line therapy in pts with mUC with FGFR alt. References: Rutkowski, et al J Clin Oncol.2019; 37 (8 suppl): 31-31. Moreno, et al. ASCO-GU Genitourinary Cancers Symposium. February 13-15, 2020. San Francisco, CA. Clinical trial information: NCT02908906 and NCT03473743 .

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