bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC).
Authors: Gainor Justin F. , Lee Dae Ho , Curigliano Giuseppe , Doebele Robert Charles , Kim Dong-Wan , Baik Christina S , Tan Daniel Shao-Weng , Lopes Gilberto , Gadgeel Shirish M. , Cassier Philippe Alexandre , Taylor Matthew H. , Liu Stephen V. , Besse Benjamin , Thomas Michael , Zhu Viola Weijia , Zhang Hui , Clifford Corinne , Palmer Michael , Turner Christopher D. , Subbiah Vivek 
Published: March 2020

9008 Background: RET fusions are targetable oncogenic drivers in up to 2% of NSCLC, yet no selective RET inhibitors are approved. BLU-667 is an investigational highly potent and selective RET inhibitor targeting oncogenic RET alterations, including those that confer resistance to multikinase inhibitors (MKIs). We provide an update on the registration-enabling ARROW study (NCT03037385) of BLU-667 in pts with RET-fusion+ NSCLC. Methods: The global ARROW study includes DE (30-600 mg daily [QD or BID]) and dose expansion (DX) at the recommended phase 2 dose (RP2D; 400 mg QD) in pts with advanced solid tumors. Primary objectives are overall response rate (ORR; RECIST 1.1) and safety. Results: As of 19Dec2018, 79 pts (21 DE, 58 DX) with advanced RET fusion+ NSCLC (44 KIF5B, 16 CCDC6, 19 other/pending) received BLU-667. Median number of prior therapies was 2 (range 0-8) and includes chemotherapy (76%), immunotherapy (41%), and MKI (27%). 39% had baseline brain metastases. ORR among 57 response-evaluable pts with measurable disease and at least one follow-up disease assessment was 56% (95% CI: 42, 69; 32 partial responses (PR), 9 PR pending confirmation, 20 stable disease, 5 progressive disease). 91% (29/32) of responding pts remain on treatment; 6 have achieved response duration ≥ 6 months. Disease control rate (DCR) was 91% (52/57). Among 30 pts at the RP2D previously treated with platinum chemotherapy, ORR was 60% (18 PRs; 7 pending confirmation). Responses occur regardless of prior treatment or RET fusion genotypes. Intracranial activity has been observed with shrinkage of brain metastases. 80% of NSCLC pts treated at RP2D remain on treatment and only 3% discontinued due to related adverse event. In NSCLC patients, treatment-related toxicity (TRT), generally low-grade and reversible (28% had ≥ grade 3 events), included increased AST (22%), hypertension (18%), increased ALT (17%), constipation (17%), fatigue (15%) and decreased neutrophils (15%). Conclusions: BLU-667 demonstrated potent, durable and broad antitumor activity and was well tolerated in pts with advanced RET-fusion+ NSCLC. Enrollment of the expansion is ongoing with registrational intent. Clinical trial information: NCT03037385.
IMpower150: Analysis of efficacy in patients (pts) with liver metastases (mets).
Authors: Socinski Mark A. , Jotte Robert M. , Cappuzzo Federico , Mok Tony S. K. , West Howard , Nishio Makoto , Papadimitrakopoulou Vassiliki , Orlandi Francisco J , Stroyakovskiy Daniil , Thomas Christian A. , Nogami Naoyuki , Barlesi Fabrice , Lee Anthony , Shankar Geetha , Yu Wei , Ballinger Marcus , Bara Ilze , Sandler Alan , Reck Martin 
Published: March 2020

9012 Background: Atezolizumab (atezo) + bevacizumab (bev) + chemo (carboplatin + paclitaxel [CP]; ABCP) showed improved PFS and OS vs bev + CP (BCP) in pts with chemo-naive NSCLC (IMpower150). Benefit with ABCP vs BCP extended to key subgroups, including pts with baseline (BL) liver mets, which is a poor prognostic factor in metastatic NSCLC. Similar outcomes were not seen with atezo + chemo (IMpower150 [atezo + CP; ACP]; IMpower130; IMpower132), suggesting that the addition of bev to atezo + chemo is important for conferring clinical benefit in these pts. Here we further explore characteristics and responses of pts with BL liver mets in IMpower150. Methods: 1202 ITT pts were randomized 1:1:1 to receive ABCP, ACP or BCP. Doses were: A, 1200 mg; B, 15 mg/kg; C, AUC 6 mg/mL/min; P, 200 mg/m2. Coprimary endpoints were OS and investigator-assessed PFS in ITT–wild-type pts. Exploratory analyses included efficacy and safety in pts with liver mets. Results: The data capture ≥ 20-mo follow-up in ITT pts (data cutoff: Jan 22, 2018). 162 pts had BL liver mets (ABCP, n = 52; ACP; n = 53; BCP, n = 57), with a median of 3 metastatic sites and median BL tumor SLD of 109 mm (range, 10-249). BL characteristics in these pts were generally balanced across study arms. PFS and OS were improved with ABCP vs BCP (Table). Gr 3-4 treatment-related AEs occurred in 52.1%, 36.5% and 54.5% of pts with liver mets in the ABCP, ACP and BCP arms, respectively. Conclusions: ABCP reduced the risk of death in pts with liver mets by 48% vs BCP and may represent an important new treatment option for this population. Clinical trial information: NCT02366143. [Table: see text]
A phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952).
Authors: Bazhenova Lyudmila , Redman Mary Weber , Gettinger Scott N. , Hirsch Fred R. , Mack Philip C. , Schwartz Lawrence Howard , Gandara David R. , Bradley Jeffrey D. , Stinchcombe Tom , Leighl Natasha B. , Ramalingam Suresh S. , Tavernier Susan S , Minichiello Katherine , Kelly Karen , Papadimitrakopoulou Vassiliki , Herbst Roy S. 
Published: March 2020

9014 Background: Lung-MAP is a master protocol for patients (pts) with stage IV previously treated SqNSCLC. S1400I enrolled pts who were not eligible for a biomarker-matched sub-study. Methods: S1400I is phase III randomized trial for immunotherapy-naïve patients with ECOG 0-1 not selected by PD-L1 expression. Pts were assigned 1:1 to nivolumab and ipilimumab (N+I) vs nivolumab (N). N was given at 3 mg/kg q 2w, I was given at 1 mg/kg q 6w. The primary endpoint was overall survival (OS). Secondary endpoints: investigator-assessed progression-free survival (IA-PFS), response by RECIST 1.1, and toxicity. Results: From December 18, 2015 to April 23, 2018, 275 pts enrolled and 252 determined eligible (125 N+I and 127 N). The study was closed for futility at an interim analysis. Baseline characteristics were similar across arms. mOS was 10.0 m (8.0-12.8) and 11.0 m (8.2-13.5) for N+I and N. HR 0.97 (0.71-1.31), p 0.82. mPFS was 3.8 m (2.3-4.2) and 2.9 m (1.8-3.9) for N+I and N. HR 0.84 (0.64-1.09), p 0.19. Outcomes based on PD-L1 and TBM subsets are shown in table. Response rates were 18% (12-25%) and 17% (11-24%) for N+ I and N. Median follow up for patients still alive was 17.4 m. Grade ≥3 treatment-related AEs occurred in 48(39%) of pts on N+I vs 38(31%) on N. irAE reported in 39% of pts on N+I and 34% of patients on N. Drug-related AEs led to discontinuation in 25% and 16% of pts on N+I and N. There were 5 grade 5 AE in N+I arm and 1 in N arm. Conclusions: S1400I failed to show improvement in outcomes with N+I. Study was closed for futility at interim analysis. Toxicities were not different between two arms. Clinical trial information: 02785952. [Table: see text]
Spatial and temporal heterogeneity of PD-L1 and its impact on benefit from immune checkpoint blockade in non-small cell lung cancer (NSCLC).
Authors: Hong Lingzhi , Dibaj Seyedeh , Negrao Marcelo Vailati , Reuben Alexandre , Roarty Emily , Rinsurongkawong Waree , Lewis Jeff , Gibbons Don Lynn , Sepesi Boris , Papadimitrakopoulou Vassiliki , Glisson Bonnie S. , Blumenschein George R. , Futreal Phillip Andrew , Wistuba Ignacio Ivan , Roth Jack A. , Swisher Stephen , Heymach John , Simon George R. , Lee J. Jack , Zhang Jianjun 
Published: March 2020

9017 Background: Temporal and spatial heterogeneity of PD-L1 has been reported. However, its impact on clinical benefit from immune checkpoint inhibitor (ICI) has not been clearly defined. Methods: We queried the MD Anderson Lung Cancer GEMINI database and compared PD-L1 expression (tumor proportion score by immunohistochemistry using FDA-approved antibodies) in NSCLC specimens from different organs at different time points. We assessed the predictive value of PD-L1 for benefit from ICIs in patients with metastatic NSCLC. Results: In 1398 NSCLC patients, PD-L1 level was significantly associated with biopsy sites (p = 0.007). Adrenal and liver metastases had the highest PD-L1 level and positive rate (by 1% or 50% cutoff) while PD-L1 was the lowest in bone and brain biopsies. In addition, PD-L1 was significantly higher in fresh tissues (PD-L1 staining at < 90 days after biopsy) than archival tissues (PD-L1 staining at > 90 days after biopsy), in squamous cell carcinoma than adenocarcinoma, in EGFR wild-type (WT) than EGFR mutant, in MET amplified than METWT, and in STK11WT than mutant (p < 0.01). Among 112 patients with longitudinal specimens tested, 55 (49%) had major changes with PD-L1 at different time points falling into different clinically relevant categories ( < 1%, 1-49%, > 50%). ICIs were associated with significant decrease in PD-L1 level compared to treatment-naïve counterparts (p = 0.019). Furthermore, 398 patients with EGFR/ALKWT metastatic NSCLC who received ICIs were divided into three groups based on biopsy sites including lung (n = 252); lymph node (LN, n = 85) and distant metastasis (n = 61). Higher PD-L1 level in biopsies from lung or distant metastasis was associated with significantly higher response rate, disease control rate and significantly longer progression free survival and overall survival using either 1% or 50% cutoff. However, the PD-L1 expression from LN biopsies was not associated with either response or survival in this cohort of patients. These findings remained constant in multivariate analyses. Conclusions: PD-L1 expression varies substantially across different anatomic sites and changes during clinical courses. PD-L1 in LN biopsies may not be reliable to predict clinical benefit for ICIs in NSCLC. Repeat biopsy and PD-L1 staining should be considered if only remote tissues, particularly, LN biopsies are available.
Early clearance of plasma EGFR mutations as a predictor of response to osimertinib and comparator EGFR-TKIs in the FLAURA trial.
Authors: Zhou Caicun , Imamura Fumio , Cheng Ying , Okamoto Isamu , Cho Byoung Chul , Lin Meng Chih , Majem Margarita , Gautschi Oliver , Gray Jhanelle Elaine , Boyer Michael J. , Chmielecki Juliann , Hartmaier Ryan , Bulusu Krishna , Barrett J Carl , Hodge Rachel , Saggese Matilde , McKeown Astrid , Ramalingam Suresh S. 
Published: March 2020

9020 Background: In the Phase III FLAURA trial (NCT02296125), osimertinib, a third generation EGFR-TKI, showed superior efficacy to comparator EGFR-TKIs as first line treatment for EGFR mutation-positive (EGFRm) advanced NSCLC. In an exploratory analysis, we investigated clinical outcomes associated with detection of plasma EGFRm at 3 or 6 weeks (wks) after start of treatment. Methods: Treatment-naïve patients (pts) with EGFRm (ex19del or L858R) locally advanced or metastatic NSCLC were randomized 1:1 to receive osimertinib 80 mg once daily (QD) or comparator EGFR-TKIs (gefitinib 250 mg QD or erlotinib 150 mg QD). Plasma EGFR mutation analysis was conducted at baseline (BL), wks 3 and 6 by droplet digital PCR. Clearance was defined as undetectable levels of EGFRm in ctDNA at wks 3/6, where they were detectable at BL. Progression-free survival (PFS) was investigated based on early clearance of EGFRm. Results: In total 489/556 (88%) pts (osimertinib: 244/279; comparator: 245/277) had evaluable ctDNA at BL and wks 3/6. Of these, 342/489 (70%; osimertinib: 168/244; comparator: 174/245) had detectable BL EGFRm and were included in this analysis. See table. Conclusions: Clearance of plasma EGFRm after 3/6 wks of EGFR-TKI therapy was associated with a numerical improvement in PFS. The efficacy of osimertinib was superior to comparator EGFR-TKIs regardless of clearance status. Clinical trial information: NCT02296125. [Table: see text]
Brigatinib (BRG) versus crizotinib (CRZ) in Asian versus non-Asian patients (pts) in the phase III ALTA-1L trial.
Authors: Ahn Myung-Ju , Kim HyeRyun , Yang James Chih-Hsin , Han Ji-Youn , Lee Jong Seok , Hochmair Maximilian J. , Li Jacky Yu-Chung , Chang Gee-Chen , Lee Ki Hyeong , Gridelli Cesare , Campelo Rosario Garcia , Delmonte Angelo , Kim Dong-Wan , Kerstein David , Ni Quanhong , Zhang Pingkuan , Popat Sanjay , Camidge D. Ross 
Published: March 2020

9026 Background: We report an analysis of BRG vs CRZ in Asian vs non-Asian pts with ALK inhibitor–naive, ALK+ NSCLC from ALTA-1L (NCT02737501). Methods: Pts were randomized 1:1 to BRG 180 mg QD (7-day lead-in at 90 mg) or CRZ 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints: BIRC-assessed ORR, intracranial (i) ORR, and iPFS. Results: 275 pts were randomized; 108 Asian (BRG/CRZ, n = 59/49), 167 non-Asian (n = 78/89); median age: Asian, 55/56 y; non-Asian, 60/60 y. 32/24% of Asians vs 22/28% of non-Asians received prior chemotherapy for advanced disease; 36/33% vs 24/28% had baseline CNS metastases. As of 19 Feb 2018, median follow-up was 10.1/10.0 mo (BRG/CRZ) in Asians vs 11.0/9.0 mo in non-Asians, with 12 vs 20 PFS events in Asians and 24 vs 43 in non-Asians. In Asians, median BIRC-assessed PFS (mo) was not reached (NR; 95% CI 11.2–NR) with BRG vs 11.1 (9.2–NR) with CRZ (HR 0.41 [95% CI 0.20–0.86]; log-rank P= 0.0261); in non-Asians, BRG PFS was NR (NR) vs 9.4 (7.3–NR) with CRZ (HR 0.54 [0.33–0.90]; log-rank P= 0.0132) (Table). AE profile of each drug was similar in Asians vs non-Asians. Most common any-grade AEs (≥25%) in Asians in BRG arm: diarrhea; elevated blood CPK, ALT, and AST. Discontinuation due to AE (BRG/CRZ): 8.5/6.3% in Asian pts; 14.3/10.1% in non-Asian pts. Conclusions: BRG showed comparable improvement in PFS vs CRZ both in Asians and non-Asians in ALK inhibitor–naive ALK+ NSCLC. Clinical trial information: NCT02737501. [Table: see text]
Palbociclib (P) in patients (pts) with non-small cell lung cancer (NSCLC) with CDKN2A alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.
Authors: Ahn Eugene R , Mangat Pam K. , Garrett-Mayer Elizabeth , Halabi Susan , Dib Elie G. , Haggstrom Daniel Ernest , Alguire Kathryn B. , Alvarez Ricardo H. , Calfa Carmen Julia , Cannon Timothy Lewis , Crilley Pamela A. , Gaba Anu G. , Marr Alissa S. , Sangal Ashish , Thota Ramya , Antonelli Kaitlyn R. , Islam Samiha , Rygiel Andrew Lawrence , Bruinooge Suanna S. , Schilsky Richard L. 
Published: March 2020

9041 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of NSCLC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced NSCLC, no standard treatment options, measurable disease, ECOG PS 0-2 and adequate organ function. Genomic testing was performed using commercially available tests. Pts matched to P had NSCLC with CDKN2A loss or mutation and no RB mutations. A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-nine pts were enrolled from January 2017 to June 2018; 1 pt was unevaluable for response but is included in safety analyses. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off. Demographics and outcomes are summarized in Table (N = 28). One PR and 6 SD16+ were observed for a DC rate of 29% (90% CI, 15% to 37%). 10 pts had at least one grade 3 or 4 AE or SAE at least possibly related to P with the most common being cytopenias. Other grade 3-4 AEs or SAEs at least possibly related to P included fatigue, anorexia, febrile neutropenia, myocardial infarction, sepsis, vomiting, and hypophosphatemia. Conclusions: Monotherapy with P demonstrated evidence of anti-tumor activity in heavily pre-treated NSCLC pts with CDKN2A loss or mutation . Additional study is warranted to confirm the efficacy of P in pts with NSCLC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]
Osimertinib induced cardio-toxicity: A retrospective review of FDA adverse events reporting system (FAERS).
Authors: Anand Kartik , Ensor Joe , Trachtenberg Barry , Bernicker Eric 
Published: March 2020

9044 Background: Osimertinib is an oral third generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). In the FLAURA trial (a Phase III randomized-control trial) Osimertinib arm had higher rate of cardio-toxicity compared to standard EGFR-TKIs. We queried FAERS database to find out rate of cardio-toxicity caused by Osimertinib compared to other EGFR-TKIs. Methods: We queried FAERS for “Cardiac failure”, “Electrogram QT-prolonged”, “Atrial Fibrillation(A.fib)”, “Myocardial Infarction(MI)”, “Cardiac failure congestive(CFC)” and “Pericardial Effusion(PE)” secondary to “Osimetinib”, “Erlotonib”, “Afatinib” and “Gefitinib” from 2016-2018. Disproportionality signal analysis was done by calculating Reporting Odds Ratio (ROR) with 95% confidence interval (CI). ROR was considered significant when lower limit of 95% CI was > 1. Results: Total AEs from all drugs were 5,138,230. Total AEs from all 4 TKIs were 8450, 2454 due to Osimertinib, 5836 due to other TKIs and 160 due to combination of both Osimertinib plus any of other 3 TKIs. ROR for Cardiac failure, A.fib, QT prolongation, MI, PE and CFC due to Osimertinib was 6.4(4.7-8.7), 4(2.8-5.8), 11.2(7.9-15.8), 1.6(0.9-2.6), 8.2(4.8-14) and 3.9(2.4-6.3) respectively. ROR for Cardiac failure, A.fib, QT prolongation, MI, PE and CFC on comparing Osimertinib vs other TKIs was 2.1(1.3-3.2), 2.1(1.3-3.5), 6.6(3.4-12.8), 1.2(0.6-2.3), 1.6(0.8-3.3) and 2.3(1.2-4.6) respectively. Findings are summarized in Table. Conclusions: Rate of QT prolongation, cardiac failure, CFC and A.fib were found to be higher due to Osimertinib compared to other TKIs. EKG monitoring for QT prolongation and monitoring for signs/symptoms of heart failure should be considered while using Osimertinib. [Table: see text]
Brigatinib in pretreated patients with ALK-positive advanced NSCLC.
Authors: Descourt Renaud , Perol Maurice , Rousseau-Bussac Gaelle , Planchard David , Mennecier Bertrand , Wislez Marie , Cortot Alexis B. , Guisier Florian , Gervais Radj , Galland Loick , Schott Roland , Dansin Eric , ARRONDEAU Jennifer , Auliac Jean-Bernard , Chouaid Christos 
Published: March 2020

9045 Background: Brigatinib is a next-generation ALK inhibitor initially developed in pre-treated ALK+ NSCLC. Data on the efficacy of brigatinib in real world remain rare. Methods: This retrospective multicentric study analyzed ALK-+ advanced NSCLC patients pretreated with at least two tyrosine-kinase inhibitors, including crizotinib, and enrolled in the brigatinib French early access program. The primary endpoint was investigator-assessed progression-free survival (PFS). Results: 104 patients were included (mean age, 56.6 years; never smokers, 61.5%; adenocarcinoma, 98.1%). Patients had received a median of 3 previous treatment lines, including at least 2 ALK inhibitors, mainly crizotinib then ceritinib in 93% patients. At brigatinib initiation, 59.1% had performance status 0-1, 51.9% had ≥ 3 metastatic sites, 74.5% had central nervous system metastases (CNS) and 8.8% had carcinomatous meningitis. Median duration of brigatinib treatment was 6.7 (0.06–20.7) months. Median PFS was 6.6 (95% CI, 4.8–9.9) months for the entire population. In the 91 evaluable patients, disease control rate was 78.2% (stable, 28.2%; partial response, 45.7%; complete response, 4.3%). From brigatinib start, median overall survival was 17.2 (95% CI:11.0–not reached) months. Among the 68 patients with progressive disease after brigatinib, CNS was involved in 29.4% of cases. Ten (9.6%) patients had treatment discontinuation due to intolerance or patient request. Median OS from the diagnostic of NSCLC was 75,3 (95% CI, 38,2-174,6) months. Conclusions: This study confirms the efficacy of brigatinib in a cohort of patients heavily pretreated for ALK-+advanced NSCLC. These real-world results are consistent with clinical data reported in clinical trials.
First-in-human phase 1 study of DS-1062a in patients with advanced solid tumors.
Authors: Sands Jacob M. , Shimizu Toshio , Garon Edward B. , Greenberg Jonathan , Guevara Ferdinand M. , Heist Rebecca Suk , Kobayashi Fumiaki , Noguchi Yutaka , Okajima Daisuke , Tajima Naoyuki , Spira Alexander I. , Yamamoto Noboru , Lisberg Aaron Elliott 
Published: March 2020

9051 Background: DS-1062a is a trophoblast cell-surface antigen 2 (TROP2)-targeting antibody drug conjugate. TROP2 is highly expressed in epithelial cancers, including non-small cell lung cancer (NSCLC). Overexpression of TROP2 may be associated with poor survival in some solid tumors. Preclinical studies showed promising antitumor activity of DS-1062a in mouse models with TROP2-positive tumors. Preliminary results are reported in the dose escalation part of this phase 1 study. Methods: This is an ongoing phase 1 study of DS-1062a in patients (pts) with advanced solid tumors in the US and Japan (NCT03401385). Adult (age ≥20 years in Japan or ≥18 years in US) pts with measurable disease per RECIST v1.1 and sufficient tumor tissue sample for TROP2 measurement were eligible. Pts were excluded if they had multiple primary malignancies or untreated brain metastases. Endpoints included safety, pharmacokinetics, and efficacy. Results: As of November 16, 2018, 22 pts with advanced NSCLC were treated with DS-1062a at doses of 0.27-mg/kg (n = 4), 0.5-mg/kg (n = 5), 1.0-mg/kg (n = 7), and 2.0-mg/kg (n = 6). Overall, mean (standard deviation) treatment duration and cumulative dose were 7.8 (4.1) weeks and 181.8 (141.4) mg, respectively, with a median of 2 (range 1–6) cycles initiated. The majority (n = 18; 81.8%) of pts had ≥1 treatment-emergent adverse event (TEAE). The most common TEAE, fatigue (n = 9), was the only grade ≥3 treatment-related TEAE (n = 1; 2.0-mg/kg). Serious TEAEs, reported in 5 pts in the 0.27-mg/kg (n = 2), 0.5-mg/kg (n = 2), and 2.0-mg/kg (n = 1) cohorts, were not treatment-related. TEAEs leading to discontinuation occurred in 1 pt in the 0.27-mg/kg cohort (pleural effusion; not treatment-related). One pt died due to progressive disease. Peak concentration (Cmax) and area under the curve from time 0 to last measurable concentration (AUClast) increases were generally dose proportional. Of 18 tumor evaluable pts, 1 had a partial response (PR; 1.0-mg/kg), and 8 had stable disease (SD). Conclusions: DS-1062a was well tolerated at doses up to 2.0-mg/kg. An observable PR and multiple pts with SD warrant further evaluation of DS-1062a. The maximum tolerated dose has not been reached, and this study is ongoing. Clinical trial information: NCT03401385.