bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot study of nivolumab in pediatric patients with hypermutant cancers.
Authors: Morgenstern Daniel A. , Collins Natalie Bucheimer , Deyell Rebecca , Dvir Rina , Edwards Melissa , Faure-Conter Cecile , Hassall Timothy E. , Sambira Lauren , Taylor Emily L. , Tabori Uri , Bouffet Eric 
Published: June 2021

10011 Background: Responses to immune checkpoint inhibitors (ICI) in unselected pediatric solid tumors have been disappointing. We hypothesized that pediatric cancers with an increased tumor mutation burden (TMB) and/or replication repair deficiency (RRD) may be uniquely susceptible to ICI therapy. Methods: OZM-075 (NCT2992964) is a multicenter pilot study in patients (pts) aged 1-25 yrs with relapsed/refractory cancers (including CNS tumors). Pts were eligible only if tumor showed evidence of RRD (based on immunohistochemistry showing loss of expression of relevant RR protein) or elevated TMB > 5mut/Mb determined by gene panel DNA sequencing. Pts with measurable or evaluable disease were eligible. Enrolment began in May 2017 and was completed in Nov 2020. Pts received programmed death-1 (PD-1) inhibitor nivolumab (NIVO) at a fixed dose of 3mg/kg every 2 weeks. Primary objective was objective response rate (ORR) by iRECIST or iRANO for those with measurable disease. Tumor tissue and serial blood samples were collected for analysis of biomarkers of response and survival. Results: As of 26Jan2021, 6 male and 5 female patients aged 9-18 yrs received treatment with NIVO (5 glioblastoma (GBM), 2 anaplastic astrocytoma (AA), 2 neuroblastoma, 1 colorectal adenocarcinoma (CRC), 1 adrenocortical carcinoma). 3pts had TMB 5-10mut/Mb, 5pts had TMB > 10mut/Mb (range 14-837, median 64), 3 pts enrolled on basis of RRD. Time on treatment ranged from 0-21 months and 2 pts remain on therapy. Best OR was partial response (PR) in 2 pts (both GBM), with an additional patient with CRC achieving pathological CR. Remarkably one of the pts with PR showed early evidence of progression on imaging and elected to discontinue NIVO. Without further therapy, subsequent imaging 7 months later showed PR. Best response of stable disease was demonstrated in 5 further pts, lasting ≥5 months in 3 pts. Median overall survival (OS) not reached. Of 7 patients with relapsed GBM/AA, 5 were alive for ≥12 months following start of NIVO including 4 pts with confirmed TMB > 10mut/Mb. Conclusions: This pilot study showed evidence of impressive clinical benefit particularly for relapsed GBM/AA patients for whom median survival is typically ̃6 months (JCO 1995 13(1):112-). These data contrast previous pediatric data and suggest that in the context of RRD and hypermutation ICI therapy may provide profound long-term response and survival for these children. Analysis of other correlative biomarkers is ongoing. Clinical trial information: 2992964.
Naxitamab and GM-CSF for consolidation of high-risk neuroblastoma (HR-NB) patients in complete remission.
Authors: Mora Jaume , Castañeda Alicia , Perez-Jaume Sara , Gorostegui Maite , Santa-María Vicente , Muñoz Juan Pablo , Varo Amalia , Mañe Salvador 
Published: June 2021

10021 Background: Naxitamab was recently approved in the US in combination with GM-CSF for the treatment of patients (pts) with relapse/refractory HR-NB in the bone/bone marrow who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we describe the use of 5 cycles of naxitamab and GM-CSF through compassionate use for consolidation of HR-NB pts in first or subsequent complete remission (CR). Methods: HR-NB pts in CR (first or subsequent) after initial multimodal induction treatment were eligible. Disease status was assessed at study entry by histology of BM biopsies/aspirates obtained from bilateral posterior and bilateral anterior iliac crests, I-MIBG SPECT scan, and whole body MRI. FDG-PET was used for MIBG non-avid cases at diagnosis. Quantitative reverse transcription-polymerase chain reaction was used to assess MRD in pooled heparinized BM aspirates. Disease response was defined according to the revised INRC. Four BM aspirates and 123I-MIBG SPECT scan or FDG-PET scans were performed after cycles 2 and 5 and every 3 months thereafter for one year in all pts to assess response. Naxitamab was administered over ≥30 min in the outpatient setting on Days 1, 3 and 5 at 3.0 mg/kg/infusion (9.0 mg/kg/cycle) in combination with GM-CSF at 250 ug/m2/day on Days -4 to 0 and at 500 ug/m2/day on days 1 to 5. Treatment cycles were repeated every 4 weeks. Survival curves were built from the time of naxitamab treatment initiation by Kaplan-Meier methods and compared using the log-rank test. Results: From June 2017 to November 30 2020, 73 pts were treated: 55 (75%) in first CR and 18 (25%) in second or more CR. Majority of pts were MYCN non-amplified (n=56, 77%), all stage 4, median age at treatment initiation 4.5 years. 61 (84%) pts had received >5 cycles of induction chemotherapy; 22 (30%) high-dose chemotherapy and autologous stem cell transplant (ASCT); and 36 (49%) radiotherapy before receiving naxitamab. 58 (79.5%) pts completed naxitamab therapy, 53 (73%) in continued CR. 10 (14%) pts relapsed during treatment and 5 (7%) had grade 4 toxicities: 2 apnea related to naxitamab; and 2 non-related: 1 opioid related chest rigidity syndrome and 1 stroke. 3-y event-free-survival (EFS) for all pts is 58% [95% CI, 43.5; 78.4], 74% for first CR and 19% for second or more CR (p=0.0029). 3-y OS for the whole group is 82% [95% CI, 66.8; 100.0], 92% for first CR and 66% for second or more CR pts (p=0.18). Univariate Cox models for CR group, MYCN status, number of chemotherapies, ASCT, radiotherapy, MRD, and age showed significant p value only for prior relapse as predictor of EFS (p=0.047). Conclusions: Naxitamab for HR-NB pts in CR provided excellent 3-y OS rates regardless of previous management. The only predictor for relapse is prior history of recurrence.
Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for metastatic breast cancer with hormone receptor-positive and HER2-positive: The sysucc-002 randomized clinical trial.
Authors: Yuan Zhongyu , Huang Jia-Jia , Hua Xin , Zhao Jian-Li , Lin Ying , Zhang Yuan-Qi , Wu Zhiyong , Zhang Lehong , Bi XiWen , Xia Wen , Zhong Yong-yi , Wang Shu-Sen , Xu Fei , Hong Ruoxi , Jiang Kuikui , Shi Yanxia , Xue Cong , An Xin 
Published: June 2021

1003 Background: For metastatic breast cancer with hormone receptor-positive and HER2-positive, no evidence showed that which first-line regimens were preferred, either anti-HER2 therapy plus endocrine therapy or anti-HER2 therapy plus chemotherapy. This study aimed to determine whether trastuzumab plus endocrine therapy is as efficacious as trastuzumab plus chemotherapy and with decreased toxic effects. Methods: We conducted an open-label, non-inferiority, phase 3, randomized, controlled trial at nine hospitals in China. Patients with hormone receptor-positive and HER2-positive histologically confirmed advanced breast cancer were randomly assigned (1:1) to receive trastuzumab plus chemotherapy (CT group) or endocrine therapy (ET group). The primary endpoint was progression-free survival with a non-inferiority upper margin of 1.35 for the hazard ratio (HR). This trial is registered with ClinicalTrials.gov, number NCT01950182. Results: Between Sep 16, 2013, and Dec 28, 2019, 392 patients were enrolled and randomly assigned to receive trastuzumab plus endocrine therapy (n = 196) or trastuzumab plus chemotherapy (n = 196). In the intention-to-treat population, the median PFS was 14.8 months (95% CI 12.8-16.8) in the CT group and 19.2 months (95% CI 16.7-21.7) in the ET group (HR 0.88, 95% CI 0.71-1.09; Pnon-inferiority < 0.0001). Significantly higher frequency of toxicities were observed in CT group compared with ET group, including: leucopenia (98 [50%] vs 13 [6.6%]), nausea (93 [47%] vs 24 [12%]), fatigue (47 [24%] vs 31 [16%]), vomiting (45 [23%] vs 12 [6%]), headache (65 [33%] vs 24 [12%]) and alopecia (125 [64%] vs 8 [4%]). No patients died from treatment-related causes. Conclusions: Trastuzumab plus endocrine therapy was non-inferior to and had decreased toxicities to trastuzumab plus chemotherapy in patients with metastatic breast cancer with hormone receptor-positive and HER2-positive. Trastuzumab plus endocrine therapy could provide more convenient treatment and allow better treatment tolerance. Clinical trial information: NCT01950182 .
Molecular characterization of the Ras-MAPK pathway in metastatic breast cancer.
Authors: Tiu-lim Justin Wayne Wong , Yin Jun , Xiu Joanne , Korn Wolfgang Michael , Lenz Heinz-Josef , In Gino Kim , Roussos Torres Evanthia T. , Lu Janice M. , Spicer Darcy V. , Xia Bing , Hoon Dave S. B. , Krill-Jackson Elisa , Heeke Arielle Lutterman , Sammons Sarah , Isaacs Claudine , Ademuyiwa Foluso Olabisi , Ma Cynthia X. , Tan Antoinette R. , Kang Irene 
Published: June 2021

1034 Background: The Ras-MAPK pathway is a known driver of tumorigenesis and therapeutic target in a variety of cancers. Alterations in this pathway have been linked to decreased tumor immunogenicity. However, molecular alterations in the Ras-MAPK are rare in breast cancer (BC) and their clinical implications remain unclear. As mutational status does not accurately correlate with transcriptional activity, a MAPK pathway activity score (MPAS, Wagle et al., 2018, npj Precision Medicine) is indicative of MAPK activation and correlates with response to MEK (MEKi) or BRAF inhibition (BRAFi). Our goal was to determine the frequency of molecular alterations in the Ras-MAPK and correlate to MAPK pathway activation in MBC. Methods: A total of 6464 BC samples underwent comprehensive molecular profiling at Caris Life Sciences. Analyses included next generation sequencing of DNA (592 Gene Panel, NextSeq; whole exome sequencing, NovaSEQ), RNA (NovaSeq, whole transcriptome sequencing, WTS) and IHC. MPAS and immune cell fraction (ICF, Quantiseq) were assessed by mRNA analysis. Wilcoxon, Fisher’s exact, or Dunnett’s test was used. All results shown were statistically significant (p < 0.05). Results: The predominant alteration of RAS genes was mutation followed by amplification, no fusions were detected (Table). Only 0.17% of all tumors harbor KRAS G12c mutations. The highest MPAS scores were found in KRAS mutants (mut), HRAS mut (Q61, G1213), BRAF V600 (class 1) mut and NRAS Q61 mut (Table) and therefore used to define Genomic MAPK Activated Tumors (GMAT). GMAT compared to wild type (WT) had significantly higher PD-L1 expression, TMB and MSI/dMMR. GMAT had less B cells (3.4% vs 4.4%), more M1 Macrophages (4.4% vs 3.4%) and neutrophils (5.5% vs 2.7%) regardless of HR status but less NK cells (2.3% s 3.0%), MSDCs (0.9% vs 3.0%) only in HR- tumors with respect to WT. GMAT tumors showed more frequent mutation rate (mr) of PIK3CA (HR+: 57.3% vs 40%; HR-: 41.9% vs 17.9%). HR+ tumors had a higher mr of MSH3 (11.8% vs 0.6%) while HR- tumors had higher mr of PIK3R1 (9.6% vs 3.8%), RhoA (5.3% vs 0.5%), DNA repair genes (TERT, 18.2% vs 1.0%; ARID1A, 18.2% vs 5.9%; PRKDC, 3.9% vs 0) and lower TP53 mr (54.5% vs 85.8%) compared to WT. Conclusions: Our study demonstrates that RAS, BRAF and MEK1 mutations are associated with MAPK pathway activation indicative of benefit from MEKi or BRAFi. GMAT warrant further investigation for combinations targeting the RAS-MAPK pathway and immune checkpoint inhibitors.[Table: see text]
Pyrotinib plus capecitabine for HER2-positive metastatic breast cancer patients with brain metastases (PERMEATE): A multicenter, single-arm phase II study.
Authors: Yan Min , Ouyang Quchang , Sun Tao , Niu Limin , Yang Jin , Li Li , Song Yuhua , Hao Chunfang , Chen Zhanhong 
Published: June 2021

1037 Background: HER2-positive metastatic breast cancer (BC) has a high risk of brain metastases (BM), leading to poor survival. Small molecule tyrosine kinase inhibitor (TKI) with enhanced penetrability to the blood brain barrier combined with capecitabine have demonstrated promising clinical outcomes in HER2-positive metastatic BC patients with untreated (such as lapatinib) or previously treated (such as neratinib) BM. The randomized phase III PHOEBE trial has proved better efficacy of pyrotinib, an irreversible pan-HER receptor TKI, versus lapatinib when in combination with capecitabine in HER2-positive local relapsed or metastatic BC. This study was conducted to investigate the efficacy and safety of pyrotinib plus capecitabine in HER2-positive metastatic BC patients with BM. Methods: In this multicenter phase II trial (NCT03691051), eligible patients received pyrotinib 400 mg orally once daily without breaks and capecitabine 1000 mg/m2 orally twice daily for 14 days followed by 7 days off. Treatment was continued until disease progression or intolerable toxicity. Prior HER2 TKIs were not allowed. Cohort A included patients with radiotherapy-naive BM, and cohort B included those with progressive BM after whole brain radiotherapy or stereotactic conformal radiotherapy. The primary endpoint was confirmed central nervous system (CNS) objective response rate (ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. Results: Between January 2018 and July 2020, a total of 78 female patients were included (Table). For cohort A (n = 59), the CNS ORR was 74.6% (95%CI: 61.6%-85.0%). For cohort B (n = 19), the CNS ORR was 42.1% (95%CI: 20.3%-66.5%). By the cutoff date on 25 January 2021, the median progression-free survival was 12.1 months (95%CI: 9.0-14.7) in cohort A and 5.6 months (95%CI: 3.4-10.7) in cohort B. The most common grade ≥3 adverse events were diarrhea (23.1% [18/78]), neutrophil count decreased (12.8% [10/78]), white blood cell count decreased (12.8% [10/78]), anemia (9.0% [7/78]), hand-foot syndrome (7.7% [6/78]), hypertriglyceridemia (6.4% [5/78]), and hypokalemia (5.1% [4/78]). Conclusions: Pyrotinib plus capecitabine resulted as an effective and safe treatment for HER2-positive BC patients with radiotherapy-naive BM, but the efficacy was modest in those with radiotherapy-treated BM. Clinical trial information: NCT03691051 .[Table: see text]
Mismatch repair gene alteration subtypes impact age of onset of mismatch repair-deficient cancers.
Authors: Wang Aifen , Hu Weidong , Feng Ninghan , Yin Yong , Pei Zhe 
Published: June 2021

10521 Background: This study investigated whether mismatch repair (MMR) gene alterations and alteration subtypes impacted age at onset of MMR-deficient cancers. Methods: A retrospective study of association of MMR-deficient alterations and age of onset of MMR-deficient lung, breast, prostate, bladder, colorectal, endometrial, and/or ovarian cancers was conducted by using cBIPORTAL dataset. Results: A total of 815 participants with MMR-deficient alterations were enrolled, 346 males and 469 females (median age 63 years; age range, 20-90 years). Males were diagnosed as colorectal and bladder cancer at later ages than females. When stratified by alteration type, individuals with MSH6 or PMS2 missense alterations had later ages of onset of colorectal cancer than those with no missense alterations. Participants with MSH2 AMP alterations were older at the diagnosis of endometrial cancer than those without MSH2 AMP alterations. Females with MLH1 missense alterations had later ages of onset of ovarian cancer than those with no missense alterations. Individuals with PMS2 AMP alterations were confirmed with lung cancer at later ages than those with no PMS2 AMP alterations. Carriers with MSH6or PMS2 missense alterations were older at the time of diagnosis of prostate cancer than those with no missense alterations. Conclusions: Gene alterations and subtype of alterations could stratify carriers with MMR-deficiency in bespoke surveillance. The mechanism of the association of MMR-deficient alterations and alteration subtypes and age at the diagnosis of MMR-deficient cancers needs to be further study.[Table: see text]
Germline alterations among Hispanic men with prostate cancer.
Authors: Shaya Justin , Nielsen Sarah M. , Hatchell Kathryn E. , Esplin Edward D. , Nussbaum Robert Luke , Weise Nicole , Madlensky Lisa , Murphy James Don , Martinez Elena , McKay Rana R. 
Published: June 2021

10534 Background: With the growing indications for germline testing in prostate cancer (PCa), there is accumulating evidence that African American and Hispanic men with PCa are significantly under-tested compared to non-Hispanic white (NHW) men. Given this, little is known about the pathogenic germline variant landscape in Hispanic men with PCa. Methods: This was a retrospective cohort analysis of 17,256 men with PCa who underwent diagnostic germline testing through a commercial laboratory (Invitae) from 2015-2020. Self-identified Hispanic and NHW men were selected for comparative analysis. The primary endpoint was the rate of pathogenic/likely pathogenic (PLP) germline alterations in Hispanic men among 25 genes associated with PCa. Secondary endpoints included comparison of PLP rates in Hispanic vs NHW men, the rate of specific PLP alterations, and the rate of variants of uncertain significance (VUS). Fisher’s exact test was used to compare germline alteration rates for significance. Results: We identified 508 Hispanic and 12,542 NHW men with PCa who underwent testing during the study period. Median age at the time of testing was 69 vs 67 years in Hispanic vs NHW cohorts. A family history of PCa was reported in 21.1% (N=108) vs 27.3% (N=3428) in the Hispanic vs NHW cohorts, respectively (p=0.002). The PLP alteration rate was 7.1% in the Hispanic cohort and this rate was numerically lower but not significantly different when compared to the NHW cohort (9.7%) (p=0.058). A significantly higher rate of VUS was seen in the Hispanic cohort (Table). The four most frequently detected genes with PLP alterations in both cohorts were ATM, BRCA1, BRCA2, and CHEK2. Only the rate of CHEK2 alterations was significantly different between cohorts among all 25 genes analyzed (Table). Conclusions: In this analysis, the PLP alteration rate among Hispanic men was 7.1%, a much higher rate than has been previously reported, and the germline genomic landscape was similar to that of NHW men. The VUS rate was significantly higher among Hispanic men, a known consequence of under-testing among minority populations.These data support germline testing in Hispanic men with prostate cancer and emphasize the importance of improving testing rates.[Table: see text]
Impact of the sessile serrated polyp pathway on predicted colorectal cancer outcomes in the CRC-AIM model.
Authors: Kisiel John B. , Itzkowitz Steven H. , Ozbay A. Burak , Saoud Leila , Parton Marcus , Lieberman David A. , Limburg Paul J. 
Published: June 2021

10545 Background: Approximately 20–30% of colorectal cancers (CRC) arise from the serrated polyp pathway. The multitarget stool DNA (mt-sDNA) test has greater sensitivity to detect sessile serrated polyps (SSPs) than a leading fecal immunochemical test (FIT). However, most modeling analyses do not account for the contribution of the SSP pathway to risk of CRC. We used the CRC-AIM model to assess the impact of the SSP pathway on predicted CRC outcomes with mt-sDNA or FIT screening. Methods: A simulated cohort of average-risk US patients underwent triennial mt-sDNA or annual FIT screening from ages 50–75. The percentage of CRCs arising from the SSP pathway were modeled at 0% (base case), 20%, and 30%, with stool screening adherence based on theoretical (100%) or previously reported (mt-sDNA 71%; FIT 43%) rates. Published SSP sensitivities for mt-sDNA and FIT were used. All other model inputs were identical to CISNET models. Sensitivity analyses used screening adherence rates of 40–70%. Key outcomes were life-years gained (LYG), CRC incidence and CRC mortality per 1000 patients. Results: Including SSPs in the model demonstrated a greater loss of LYG with FIT than mt-sDNA (Table). At 100% adherence, compared with base case, modeling 20% or 30% SSP pathway CRCs resulted in a decrease of 9–15 LYG with FIT and 2–4 LYG with mt-sDNA, a decrease in CRC incidence reduction of 3.9–6.1% with FIT and 0.7–1.1% with mt-sDNA, and a decrease in CRC mortality reduction of 2.6–4.0% with FIT and 0.4–0.8% with mt-sDNA. Using previously reported adherence, compared with base case, modeling 20% or 30% SSP pathway CRCs resulted in a decrease of 13–20 LYG with FIT and 2–5 LYG with mt-sDNA, a decrease in CRC incidence reduction of 4.4–6.9% with FIT and 0.6–1.1% with mt-sDNA, and a decrease in CRC mortality reduction of 3.5–5.4% with FIT and 0.4–0.9% with mt-sDNA. Assuming reported adherence and 30% SSP pathway CRCs, mt-sDNA had 48 more LYG, 14.6% greater CRC incidence reduction, and 12.4% greater CRC mortality reduction than FIT. Assuming 30% SSP pathway CRCs, outcomes favored mt-sDNA vs FIT even after modeling equivalent adherence rates ranging from 40–70%. Conclusions: After incorporating the SSP pathway into the model, outcomes with mt-sDNA neared those of FIT at 100% screening adherence rates and surpassed FIT at more realistic reported screening adherence rates.[Table: see text]
AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with palbociclib (palbo) in postmenopausal women with ER+/ human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).
Authors: Chandarlapaty Sarat , Linden Hannah M. , Neven Patrick , Petrakova Katarina , Bardia Aditya , Kabos Peter , Braga Sofia A. D. S. , Boni Valentina , Gosselin Alice , Cartot-Cotton Sylvaine , Doroumian Séverine , Celanovic Marina , Cohen Patrick , Paux Gautier , Campone Mario 
Published: June 2021

1058 Background: AMEERA-1 (NCT03284957) investigates amcenestrant, an oral SERD, as monotherapy and combined with targeted therapies in ER+/HER2– mBC. Here we report data from dose escalation (Part C) and dose expansion (Part D) of amcenestrant + palbo. Methods: Patients (pts) were postmenopausal women with ER+/HER2– mBC and ≥ 6 mos prior advanced endocrine therapy (ET) or adjuvant (adj) ET resistance (relapse on adj ET started ≥ 24 mos ago or < 12 mos after completing adj ET). Prior chemotherapy (≤ 1) for advanced disease was allowed; targeted therapies were not except ≤ 1 CDK4/6i in Part C. Part C assessed dose-limiting toxicities (DLTs) and aimed to establish the recommended phase 2 dose (RP2D) for amcenestrant (200 or 400 mg once daily [QD], in 28-day cycles) in combination with palbo (125 mg QD for 21 days on/ 7 days off). Safety (treatment-emergent adverse events [TEAEs] and lab abnormalities per CTCAE v4.03) and pharmacokinetics (PK) were evaluated. Antitumor activity at the RP2D for amcenestrant + palbo was evaluated in a subset of Part C pts and Part D, according to RECIST v1.1, determined locally by investigators. Results: Feb 8, 2021 data cutoff. In Part C (n = 15; 200 mg: 9; 400 mg: 6), no DLTs occurred and amcenestrant 200 mg QD was selected as the RP2D with palbo, based on PK and safety data. In the pooled safety population at the RP2D (n = 39; Part C: 9; Part D: 30), median (range) age was 59 y (33–86) with ECOG PS 0 (74.4%) or 1 (25.6%) and 2 (1–6) organs involved. Immediate prior therapy was neo/adj (41.0%, all ET resistant) or advanced (59.0%, range 1–4 lines). Median (range) exposure was 32 wks (1–66) with 59.0% pts on ongoing therapy. No amcenestrant dose reductions occurred; 25.6% had ≥ 1 palbo dose reduction. Most common non-hematological TEAEs related to amcenestrant were Grade 1–2 nausea and fatigue (17.9% each), asthenia and hot flush (10.3% each); to palbo were fatigue (30.8%), nausea (25.6%), asthenia and dysgeusia (10.3% each). Two pts discontinued due to AEs. The majority (94.9%) had neutrophil count decrease (53.8% Grade ≥ 3). Preliminary antitumor activity after at least 6 cycles of therapy (unless early treatment discontinuation) is reported in the table below. Conclusions: In pts with ER+/HER2– mBC, safety at the RP2D of amcenestrant + palbo was favorable, with no safety signals of bradycardia or eye disorders. Preliminary antitumor activity was observed (ORR: 31.4% and CBR: 74.3%). Clinical trial information: NCT03284957 .[Table: see text]