bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and tolerability of BION-1301 in adults with relapsed or refractory multiple myeloma.
Authors: Bensinger William , Raptis Anastasios , Berenson James R. , Spira Alexander I. , Nooka Ajay K. , Chaudhry Maria , van Zandvoort Peter , Nair Nitya , Lo Jeannette , Elassaiss-Schaap Jeroen , Walling Jackie , Hari Parameswaran
Published: March 2020

8012

Background: BION-1301 (BION) is first in class humanized monoclonal antibody directed against a proliferation-inducing ligand (APRIL) for treatment of relapsed/refractory (R/R) multiple myeloma (MM). APRIL secreted by cells in the bone marrow (BM) niche binds to BCMA (B-Cell maturation antigen) and TACI (transmembrane activator and CAML interactor) expressed on human MM cells to drive their proliferation and survival. In patients (pts) with MM, serum APRIL levels are elevated and are correlated with promotion of malignancy, chemo- and immune-resistance. This study evaluated tolerability and clinical activity of BION monotherapy in R/R MM pts. Methods: Adults with MM, progression after ≥3 systemic therapies, and ECOG 0-1 were enrolled in this phase 1/2, open-label study. The phase 1 study is evaluating 6 cohorts with increasing BION doses of 50, 150, 450, 1350, and 2700 mg administered Q2W intravenously (cohort 6 - 1350 mg dose given QW and Q2W). Response was assessed by investigators Q4W. Serum was analyzed for BION, anti-drug antibodies (ADA), and soluble unbound “free APRIL” (fAPRIL) and evaluated by PK-PD modeling. Results: As of 7Dec2018, 15 pts were enrolled in 4 cohorts at doses between 50-1350 mg given Q2W. 5/15 (33%) had ECOG 0 and pts received median of 6 prior systemic therapies (range: 4-17). Related treatment emergent adverse events (TEAE) were reported in 8/15 (36%); most common related TEAE included anemia (n=3), arthralgia (n=2), and dysgeusia (n=2). 1 subject receiving 4th dose of BION experienced grade 3 wheezing considered infusion-related and serious. No dose-limiting toxicities were observed. Of 14/15 evaluable for response, no objective response was observed and 5/14 (36%) had stable disease. Median time on treatment was 2 months (range: 0.9-4.9+) and median of 3 doses of BION (range: 2-11) were administered. BION exposure increased dose proportionally from 50-1350 mg, and half-life (T1/2) and clearance (CL) did not differ significantly (median T1/2 = 9.0 days [range: 3.9-20], median CL = 0.52 L/day [range: 0.32-0.72]). Levels of fAPRIL in serum and BM decreased with increasing BION doses. By 450 mg, 95% target engagement (TG) was achieved around peak exposure levels. Non-neutralizing ADA was detected in 1/15 pts. Conclusions: BION, at doses 50-1350 mg given Q2W, was well-tolerated and dose-dependently reduces serum levels of fAPRIL. To date, objective responses have not been observed. The study is ongoing with pts exposed to higher and/or more frequent doses with the objective of achieving accelerated and sustained APRIL TG. Clinical trial information: NCT03340883.
Multimorbidity patterns and their association with survival in a large national cohort of older veterans with multiple myeloma.
Authors: Fillmore Nathanael , DuMontier Clark , Cheng David , Cirstea Diana , Yellapragada Sarvari , Pyarajan Saiju , Do Nhan , Kim Dae , Abel Gregory A. , Brophy Mary T. , Driver Jane A. , Munshi Nikhil C.
Published: March 2020

8033

Background: The majority of older adults carry two or more chronic conditions (multimorbidity). Although comorbidity in multiple myeloma (MM) has often been described with comorbidity counts, the impact of multimorbidity clusters has yet to be investigated. Methods: In a national cohort of 7815 patients aged ≥60 years diagnosed with and treated for MM in Veterans Affairs Healthcare System, we extracted 53 chronic conditions from claims in the 3 years preceding diagnosis using the Centers of Medicare and Medicaid Services-defined chronic and disabling conditions. We performed latent class analysis to identify patterns of multimorbidity that coexisted with MM at diagnosis. We then assessed whether these multimorbidity patterns were associated with survival in 5992 non-transplanted patients initially treated with either doublet or triplet chemotherapy regimens, adjusting for MM stage, sociodemographic factors, and prognostic lab values. Results: Mean follow up time was 3.1 years (SD, 2.6). We identified 6 multimorbidity clusters at the time of MM diagnosis: minimal disease (1302 patients, 16.7%), cardiovascular disease (2011, 25.7%), diabetes and complications (1820, 23.3%), psychiatric and substance use disorders (931, 11.9%), chronic lung disease (759, 9.7%), and multisystem impairment (992, 12.7%). In patients initially treated with doublet or triplet chemotherapy, survival varied across multimorbidity patterns (p < 0.001); patients with minimal disease had the best survival (median survival [MS] = 4.5 years, 5-year survival = 47.5%), and patients with multisystem impairment had the worst (MS = 2.4 years, 5-year survival = 24.3%). After adjustment for covariates, patients with clusters of chronic lung disease (HR = 1.40 [1.22-1.60]), psychiatric and substance use (HR = 1.57 [1.37-1.79]), and multisystem impairment (HR = 1.71 [1.50-1.94]) had higher hazards of death than patients with minimal disease. Conclusions: We found higher-impact and lower-impact multimorbidity clusters among older veterans with newly-diagnosed MM treated with chemotherapy. Unique combinations of chronic diseases may interact with MM itself to drive differences in mortality.
Impact of age on efficacy and safety of daratumumab in combination with lenalidomide and dexamethasone (D-Rd) in patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (NDMM): MAIA.
Authors: Usmani Saad Zafar , Facon Thierry , Kumar Shaji , Plesner Torben , Moreau Philippe , Basu Supratik , Nahi Hareth , Macro Margaret , Quach Hang , Perrot Aurore , Venner Chris , Weisel Katja , Raje Noopur S. , Attal Michel , Leleu Xavier , Krevvata Maria , Wang Jianping , Kobos Rachel , Hulin Cyrille
Published: March 2020

8035

Background: D-Rd significantly reduced the risk of progression/death by 44% in transplant-ineligible NDMM pts vs Rd in the phase 3 MAIA study. To examine the impact of age on efficacy/safety of D-Rd vs Rd in this population, a subgroup analysis was conducted in pts <75 and ≥75 y of age. Methods: Transplant-ineligible NDMM pts were randomized 1:1 to Rd ± DARA; stratification was based on age (<75 vs ≥75 y), ISS (I, II, III), and region (North America vs Other). Pts received 28-day cycles of either R 25 or 10 mg (based on renal function) PO QD on Days 1-21 and either d 40 or 20 mg (based on age or BMI) PO/IV weekly until progression. In the D-Rd arm, pts received daratumumab 16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter until progression. PFS is the primary endpoint. Results: Among 737 randomized pts (D-Rd, n=368; Rd, n=369), 321 (44%) were ≥75 y of age. For D-Rd vs Rd, relative median dose intensity for R was 79% vs 93% for <75 y subgroup and 66% vs 89% for ≥75 y subgroup, respectively. After median follow-up of 28 mo, significant PFS benefit of D-Rd vs Rd was maintained in both <75 and ≥75 y subgroups (Table). Deeper responses and MRD-negative rate (10-5 threshold) remained higher with D-Rd vs Rd in both subgroups (Table). Most common (≥10%; D-Rd/Rd) grade 3/4 TEAEs in ≥75 y pts were neutropenia (60%/41%), lymphopenia (19%/12%), anemia (16%/22%), pneumonia (15%/10%), leukopenia (12%/6%), and thrombocytopenia (8%/11%). Fewer pts receiving D-Rd vs Rd discontinued treatment due to TEAEs (<75 y: 5% vs 12%; ≥75 y: 10% vs 21%). Conclusions: D-Rd pts received less R vs Rd group regardless of age. Efficacy of D-Rd in <75 and ≥75 y pts was consistent with the ITT population, and D-Rd demonstrated acceptable tolerability regardless of age. Together with the phase 3 ALCYONE study, these studies confirm clinical benefit of daratumumab plus standard-of-care in transplant-ineligible NDMM pts ≥75 y of age. Clinical trial information: NCT02252172. [Table: see text]
Analysis of time to next treatment (TTNT) in melflufen and dexamethasone-treated patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Authors: Bringhen Sara , Richardson Paul G. , Voorhees Peter Michael , Plesner Torben , Mellqvist Ulf-Henrik , Zonder Jeffrey A. , Reeves Brandi Nikcole , Zavisic Stojan , Harmenberg Johan , Obermüller Jakob , Sonneveld Pieter
Published: March 2020

8043

Background: Melflufen is a novel peptide-conjugated alkylator potentiated by intracellular aminopeptidases, which are markedly overexpressed in MM. Melflufen + dex had encouraging activity in pts with RRMM and ≥2 prior lines of therapy in the phase 1/2 O-12-M1 study (overall response rate 31%; median overall survival of 20.7 mo; Richardson et al. ASH 2017. Abs. 3150). TTNT is used in Real World Evidence (RWE) to assist treatment decisions and support economic reimbursement modeling. We report TTNT after melflufen + dex in O-12-M1. Methods: Pts with RRMM and ≥2 prior lines of therapy, including bortezomib and lenalidomide (len) received 40 mg IV melflufen on d 1 of each 28-d cycle + 40 mg weekly dex until progressive disease (PD)/unacceptable toxicity. Pts were followed up for 2 y after PD, and TTNT was retrospectively reviewed for subsequent therapy. Results: As of 9 Nov 2017, 45 pts were treated: median age, 66 y (47-78); ISS stage II/III, 60%; high-risk cytogenetics, 44%. Pts had 4 median prior lines of therapy; 87% were refractory to last line of therapy including alkylators (24%), proteasome inhibitors (PIs; 27%), IMiDs (56%), and monoclonal antibodies (mAbs, 9%); 11% were last-line double refractory. At data cutoff, 44 pts (98%) discontinued melflufen + dex, mainly due to adverse events (40%) and PD (29%). 26 pts received subsequent therapy. Median time from start of melflufen + dex to first subsequent therapy or death, whichever occurred first, (TTNT) was 7.9 mo (95% CI: 5.7-11.0); next therapy included alkylators (27%), PIs (38%), IMiDs (58%), and mAbs (8%). Conclusions: Types of subsequent salvage therapy used after melflufen + dex were similar to studies of approved agents in RRMM; TTNT was also similar (Table). Further trials are ongoing, including melflufen + dex vs pomalidomide (pom) + dex in pts with RRMM refractory to len (Phase 3 OCEAN study; NCT03151811). Clinical trial information: NCT01897714. [Table: see text]
Chromosome 1 abnormalities and clinical outcomes in multiple myeloma in the era of novel agents.
Authors: Giri Smith , Huntington Scott F. , Wang Rong , Zeidan Amer Methqal , Podoltsev Nikolai Alexandrovich , Gore Steven , Ma Xiaomei , Gross Cary Philip , Davidoff Amy J. , Neparidze Natalia
Published: March 2020

8044

Background: Abnormalities of chromosome 1 (C1A) are common genetic mutations in patients (pts) with Multiple Myeloma (MM). While several small studies have reported worse outcomes for C1A, the prevalence, real-world treatment and outcomes for pts with C1A are unknown. Methods: We used the Flatiron Health Electronic Health Record (EHR)-derived database to identify pts with newly diagnosed MM from 01/2011 to 03/2018 with Fluorescence In situ Hybridization (FISH) testing within 90 days of diagnosis and defined lines of therapy. We identified pts with C1A and other high-risk mutations (HRM; 17p deletion, t14;16 and t4;14). Pts were followed until 3/31/2018 or death. The primary outcome was overall survival (OS). We used Kaplan Meier methods and compared OS for pts with/without C1A using log-rank tests stratified for HRM. We used Cox regression analysis to compare OS across groups, adjusting for age, gender, performance status, stage, HRM and treatment (triple regimen vs other). Results: The total sample included 3,578 pts: median age at diagnosis was 69 yrs (IQR 31-85), with 54% males and 60% whites. IgG(57%) and IgA(22%) were the most common M-protein subtypes. At baseline, 844 (24%) had C1A. Pts with C1A had higher stage (ISS III 35% vs 26%; p < 0.01) and other HRM (27% vs 14%, p < 0.01). Common first line-therapies included bortezomib(V), lenalidomide(R) and dexamethasone (D) (35%), RD (20%) followed by VD(15%). Use of VRD was higher with C1A vs without (40% vs 33% respectively, p < 0.01). Median OS was 66.9 months for the entire cohort and was lower for pts with C1A vs without (median OS 46.6 vs 70.1 months; log rank p < 0.01). Multivariable Cox survival analysis showed that C1A was independently associated with worse OS (adjusted HR 1.64; 95% CI 1.23-2.19); p < 0.01). Other predictors of worse survival included older age, black ethnicity, higher ISS stage, poor performance status and HRM. Conclusions: In this large study of real-world practice, C1A was associated with inferior OS independent of other HRM, despite higher use of VRD. Future studies are needed to assess whether specific regimens improve outcomes for C1A compared to patients without HRM.
Project Switch: Lenalidomide and dexamethasone (Len-Dex) as a potential synthetic control arm (SCA) in relapsed or refractory multiple myeloma (rrMM).
Authors: Kanapuru Bindu , Gong Yutao , Mishra-Kalyani Pallavi Shruti , Menefee Michael E. , Sridhara Rajeshwari , Farrell Ann T. , Blumenthal Gideon Michael , Pazdur Richard
Published: March 2020

8047

Background: Len-Dex is a common comparator arm to test novel therapies in rrMM trials. There is interest in evaluating if the control data from one clinical trial can be borrowed to another clinical trial, thus creating SCAs which could potentially improve accrual to trials, make better go/no-go decisions, and increase patients access to promising experimental therapies (ETs). We looked at legacy rrMM trials to assess the impact of switching and pooling Len-Dex control arms among different trials when evaluating ETs. Methods: We identified 4 contemporary rrMM trials that enrolled 2,729 patients testing ET + Len-Dex vs. Len-Dex alone. We calculated progression-free survival (PFS), Hazard Ratio (HR) and 95% Confidence Interval (CI) for ET compared to the original trial control, the switch Len-Dex controls, a pooled Len-Dex control, and a matched pooled control using bootstrapping sampling methods to match the experimental arm baseline demographics and prior lines with the pooled control. Results: See table. Conclusions: In this analysis, the switch and pooled controls matched the original control for Trials 1 and 2, but not for Trials 3 and 4. The bootstrapping methods did not substantially assist in replicating the original results. This could be due to several factors including heterogeneity of the enrolled populations including different lines of therapy, different pharmacologic classes of drugs studied in the ETs, and missing prognostic data including cytogenetics. Further investigations into propensity score matching will be explored to determine if SCAs can be improved.[Table: see text]
Randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine /cisplatin (Vnr/Cis) for completely resected stage II-IIIA non-squamous non-small-cell lung cancer (Ns-NSCLC): The JIPANG study.
Authors: Kenmotsu Hirotsugu , Yamamoto Nobuyuki , Yamanaka Takeharu , Yoshiya Katsuo , Takahashi Toshiaki , Ueno Tsuyoshi , Goto Koichi , Daga Haruko , Ikeda Norihiko , Sugio Kenji , Seto Takashi , Toyooka Shinichi , Date Hiroshi , Mitsudomi Tetsuya , Okamoto Isamu , Yokoi Kohei , Saka Hideo , Okamoto Hiroaki , Takiguchi Yuichi , Tsuboi Masahiro
Published: March 2020

8501

Background: Although previous trials demonstrated the efficacy and safety of postoperative cisplatin–based adjuvant chemotherapy for resected NSCLC, no phase III study has so far evaluated Pem/Cis in this population. Methods: Patients with completely resected pathological stage II-IIIA Ns-NSCLC were randomized in a 1:1 ratio to receive either Pem (500 mg/m2, day 1)/Cis (75 mg/m2, day 1) or vinorelbine (Vnr) (25 mg/m2, days 1 and 8)/Cis (80 mg/m2, day 1), and stratified according to sex, age, pathologic stage, EGFR mutation status and institution. The primary endpoint was recurrence-free survival (RFS), and, the planned sample size was 800 patients in total to detect the superiority of Pem/Cis over Vnr/Cis (Trial Identifier, UMIN000006737). Results: Between March 2012 and August 2016, 804 patients were randomized. Of 784 for the efficacy analysis (389 in Pem/Cis and 395 in Vnr/Cis), median age was 65/65 years; stage IIIA 52/52%; Adenocarcinoma, 96/96%; and EGFR mutation, 24/25%. With a median follow-up of 45.2 months (mo), median RFS was 38.9mo in Pem/Cis and 37.3mo in Vnr/Cis with a hazard ratio (HR) of 0.98 (95% CI, 0.81—1.20; log-rank test, P= 0.948), whereas HRs in patients with and without EGFR mutations were 1.38 (95% CI, 0.95—1.99) and 0.87 (95% CI, 0.69—1.09), respectively (Interaction, P= 0.046). Overall survival rate at 3 years was 83.5% versus 87.2% with a HR of 0.98 (95% CI, 0.71—1.35). Incidences of grade 3 or 4 febrile neutropenia (0.3/11.6%, P< 0.001), neutropenia (22.8/81.1%, P< 0.001), and anemia (2.8/9.3%, P< 0.001); any grade alopecia (12.8/30.1%, P< 0.001). One treatment-related death was observed in each arm. Rates of treatment completions were 87.9% (Pem/Cis) and 72.7% (Vnr/Cis), respectively (P < 0.001). Conclusions: Although this phase III study did not meet the primary endpoint, Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability as postoperative adjuvant chemotherapy for Ns-NSCLC patients. A significant interaction for RFS was found between treatment and EGFR mutation status. Clinical trial information: UMIN000006737.
Phase II trial of carfilzomib and irinotecan in relapsed small cell lung cancer (NCT01941316).
Authors: Arnold Susanne M. , Chansky Kari , Baggstrom Maria Quintos , Thompson Michael A. , Sanborn Rachel E. , Villano John , Waqar Saiama Naheed , Hamm John Turner , Leggas Mark , Willis Maurice , Rosales Joseph G , Crowley John
Published: March 2020

8513

Background: Relapsed small cell lung cancer (SCLC) is incurable with limited therapeutic options. This phase II study evaluated efficacy and tolerability of carfilzomib + irinotecan in SCLC pts who progressed after prior platinum-based therapy, based on expected synergy of proteosome inhibitor carfilzomib and topisomerase 1 inhibitor irinotecan. Methods: SCLC pts who progressed after one platinum-containing regimen (no maintenance therapy allowed) for recurrent/metastatic disease were eligible. Pts were stratified by response to platinum-based therapy: sensitive (progressive disease (PD) > 90 days after chemo) versus refractory (PD 30 to 90 days after chemo). Pts were treated with up to 6 cycles of carfilzomib (20/36 mg.m2 D1, 2, 8, 9, 15, 16 q28D) and irinotecan (125 mg/m2 D1, 8, 15 q28D), imaging was performed every 2 cycles. The primary efficacy endpoint was 6-month overall survival (OS). Results: 62 pts enrolled and were evaluable for efficacy and adverse events. The 6-month OS was 59% in the platinum sensitive stratum and 54% in the platinum refractory stratum. Overall response rate: sensitive stratum 21.6% (1.6% CR + 16.4% PR) and refractory stratum 12.5% (all PR). Disease control (SD+PR+CR) was 68% in platinum sensitive and 56% in refractory patients. Progression free survival and OS were 3.6 months (95% CI 2.6 - 4.6) and 6.9 months (95% CI 4.3 - 12.3) in the sensitive stratum, and 3.3 months (95% CI 1.8 – 3.9) and 6.8 months (95% CI 4.1-11) in the refractory stratum. Twenty-nine pts (47%) experienced at least one grade 3 AE and 8 subjects had grade 4 toxicities: decreased neutrophils, leukocytes, and lymphocytes, diarrhea, vomiting, sepsis, hypokalemia, hypocalcemia, and dehydration. There were three treatment related deaths: myocardial infarction (possible), lung infection (possible), sepsis (probable). Conclusions: In previously treated pts with relapsed SCLC, irinotecan and carfilzomib was effective in platinum-sensitive and, notably, platinum-refractory pts with similar toxicity profile. This combination is a viable option in relapsed SCLC, can be considered following progression on immunotherapy (IO) or in subjects who cannot receive IO, and should be further explored in a randomized phase III trial. Clinical trial information: NCT01941316.
Phase II, prospective single-arm study of adjuvant pembrolizumab in N2 positive non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy followed by curative resection: Preliminary results.
Authors: Ahn Myung-Ju , Park Sehhoon , Jung Hyun Ae , Cho Jong Ho , Sun Jong-Mu , Lee Se-Hoon , Choi Yong Soo , Ahn Jin Seok , Kim Jhingook , Park Keunchil , Zo Jae Ill , Shim Young Mog , Kim Kyung Hwan , Shin Eui-Cheol , Kim Hong Kwan
Published: March 2020

8520

Background: The standard treatment option for stage IIIA-N2 subgroup is still under discussion with controversies. We hypothesize that immune checkpoint inhibitor consolidation therapy could have an additional role in prolongation of the disease-free survival (DFS) for stage IIIA-N2 NSCLC treated with tri-modalities therapy. Methods: This is a phase 2 study evaluating the clinical efficacy of pembrolizumab treatment after CCRT with curative resection in stage IIIA-N2 NSCLC pts. Pathologically confirmed pts were treated with five cycles of CCRT, weekly paclitaxel (50mg/m2) and cisplatin (25mg/m2) combined with radiotherapy (total of 44Gy over 22 fractions) followed by curative resection. Adjuvant Pembrolizumab (200mg fixed dose) is applied every three weeks up to 2 years or until disease recurrence. The primary objective is disease-free survival of more than 20 months. The first patient was recruited in October 2017, and the data for this abstract was locked at 20th of January, 2019. Results: Total of 40 pts were screened, and 37 pts received treatment. Median age was 64 years (range 39-74), and twenty-three pts were male (62.2%). As a curative surgery, pts received lobectomy (n=34), bi-lobectomy (n=2), or pneumonectomy (n=1). Adenocarcinoma was predominant (n=27, 73.0%). After the neoadjuvant CCRT, down-staging were observed in nine pts (24.3%). The median follow-up duration was 10.6 months (range 3.1-17.2), and pts received a median of 11 cycles (range 1-22) of adjuvant pembrolizumab. DFS is not reached. Fourteen patients discontinued treatment due to disease progression (n=9), adverse events (n=4) and withdraw consent (n=1). There was a case of grade 4 pneumonitis and a case of grade 3 autoimmune hepatitis which lead to discontinuation of the treatment. Otherwise, grade 1-2 hypothyroidism (n=6), pneumonitis (n=5), skin rash (n=3) were observed. Patients with sever immune-related adverse event showed a significantly high percentage of Ki-67 + cells among CD8 T-cells in peripheral blood. Conclusions: This study is the first study to demonstrate the feasibility of adjuvant pembrolizumab monotherapy in stage IIIA-N2 patients. Updated and detail clinical and exploratory biomarker outcome will be presented at the annual meeting. Clinical trial information: NCT03053856.
Neoadjuvant pembrolizumab (Pembro) for early stage non-small cell lung cancer (NSCLC): Updated report of a phase I study, MK3475-223.
Authors: Bar Jair , Urban Damien , Ofek Efrat , Ackerstein Aliza , Redinsky Ilanit , Golan Nir , Kamer Iris , Simansky David , Onn Amir , Raskin Stephen , Shulimzon Tiberiu , Peled Michael , Zeitlin Nona , Halparin Sharon , Jurkowicz Menucha , Abukhalil Ramez , Perelman Marina , Ben-Nun Alon
Published: March 2020

8534

Background: Resected NSCLC clinical stage I or II harbor a 5 year survival of only 30-50%. Immunotherapy might be more effective in low-burden disease. We hypothesized that neo-adjuvant immunotherapy is a feasible, safe and effective treatment (Tx) for early stage NSCLC. Methods: MK3475-223 is an ongoing phase I study of neoadjuvant pembrolizumab in stage I-II NSCLC. All Pembro Txs are 200mg q 3 weeks (wks). Objectives: determine safety; recommended phase 2 dose/schedule; pathological & radiological response. Doses-schedule limiting toxicities (DLT) were defined as significant surgical complications (bleeding, delayed wound healing, ARDS, prolonged air-leak) or a significant delay of surgery. The doses-schedule escalation cohorts were (i) single pembro dose 3 wk prior to surgery; (ii) 2 pembro doses, 2 wks later surgery; (iii) 2 pembro doses, 1 wk later surgery. Expansion cohort received the doses-schedule of cohort (iii). Percentages of remaining viable tumor in the post-Tx were assessed, 10% or less was considered amajor pathological response (MPR). IHC for pre-Tx PDL1 was done. Efficacy was evaluated for the patients who had received 2 doses of pembrolizumab. Results: No DLT occurred in the dose-schedule escalation cohorts. 10 patients received 2 cycles of neo-adjuvant pembrolizumab. 4 patients achieved a MPR (4/10 who received 2 cycles of pembro; 40%; 95% C.I. 16.7-68.8%). No correlation is seen between the levels of PDL1 pre-Tx and the pathologic response. Size of the tumor and N status was also not in any apparent correlation with MPR (data not shown). Interestingly, all of the MPR cases had a relatively long interval from 1st Tx till surgery. Clinical trial information: NCT02938624. Conclusions: Neo-adjuvant pembro is safe and feasible. A promising sign of efficacy is seen. Achieving MPR might require a longer 1st-Tx-surgery interval. Predictive biomarkers for response might be different from those in advanced disease. Recruitment and correlative studies are ongoing.[Table: see text]
Comprehensive genomic profiling in Chinese patients with lung squamous cell carcinoma.
Authors: Lian Zuping , Li Heng , Lei Youming , Xian Lei , Bu Kunpeng , Wang Xiangping , Chen Zhonghai , Guo Honglin , Chen Xiaoqian , Guo Fei , Zhang Lin
Published: March 2020

8540

Background: Lung squamous cell carcinoma (LUSC) is a major histological subtype of non-small cell lung cancer (NSCLC) and accounts for 30% of NSCLC. Previous studies had revealed the genomic characterization of LUSC in Western patients (pts). However, the comprehensive genomic features of LUSC in Chinese pts have not been well understood. Methods: Deep sequencing targeting 450 cancer genes was performed on FFPE and matching blood samples collected from 311 LUSC pts. Genomic alterations (GAs) including single nucleotide variations, short and long insertions and deletions, copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Results: The median age of LUSC pts was 63 years old (range 57-68.5), of which 88% were male. The most frequently mutated genes were TP53 (88%), PIK3CA (34%), CDKN2A (33%), SOX2 (26%), LRP1B (22%), KLHL6 (21%), KMT2D (19%), PRKCI (19%), NFE2L2 (18%) and MAP3K13 (17%). Interestingly the mutation rates of PIK3CA (p = 1.93e-05) and CDKN2A (p = 2.48e-05) were significantly higher than that in TCGA cohort. Genomic alterations in eight druggable genes recommended by the NCCN guideline occurred in 32% of pts, and alterations to PI3K/mTOR signaling pathway related genes occurred in 52% of pts. One patient with PIK3CA amplification achieved stable disease for eight months after everolimus treatment. Moreover, variants in the homologous recombination (HR) pathway were identified in 17% of pts. The median TMB of LUSC pts was 10.8 Muts/MB (range 6.9-14.5 Muts/MB) which was higher than Western populations [PMID: 28420421]. The 1st Quartile (TMB-L), median and 3rd Quartile (TMB-H) TMB value was 6.9, 10.8 and 14.5 Muts/Mb respectively. Comparing with the TMB-L group, frequencies of CDKN2A (39% vs 19%, p= 0.005), LRP1B (45% vs 8%, p< 0.001) and KMT2D (27% vs 8%, p= 0.002) were higher in TMB-H group. Conclusions: In summary, we characterized the genomic alteration profile of Chinese LUSC pts. Consistent with previous reports, high mutation rates of TP53, PIK3CA and CDKN2A are the most important genomic features of LUSC. However, the proportion of PIK3CA and CDKN2A mutations in Chinese LUSC pts is higher than that of Western populations. In addition, we also found targetable pathways (including PI3K/mTOR) along with gene related variations and high TMB in many pts, providing potential targeted therapy and immunotherapy options for LUSC pts.
Phase I study on preliminary safety and efficacy of rovalpituzumab tesirine in Japanese patients (pts) with advanced, recurrent small cell lung cancer (SCLC).
Authors: Akamatsu Hiroaki , Udagawa Hibiki , Tanaka Kentaro , Takeda Masayuki , Kanda Shintaro , Kirita Keisuke , Teraoka Shunsuke , Nakagawa Kazuhiko , Fujiwara Yutaka , Yasuda Ikuko , Okubo Sumiko , Shintani Masayuki , Leibman Rachel S , Scripture Charity D. , Tamura Tomohide , Okamoto Isamu
Published: March 2020

8557

Background: SCLC rapidly recurs after first-line platinum therapy, and while several agents are approved in the relapsed/refractory setting, there is no approved agent or existing standard of care for third-line in Japan. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting Delta-like 3 protein (DLL3), an atypical Notch ligand that is highly expressed in SCLC but not in normal tissue. This was the first study evaluating safety, PK, and preliminary anti-tumor activity of Rova-T in Japanese pts. Methods: This was an open label Phase 1, 3+3 dose-escalation study of Rova-T in Japanese pts with advanced recurrent SCLC (NCT03086239). Eligibility: progressive disease after ≥2 prior systemic regimens incl. ≥1 platinum-based regimen; ECOG 0-1. Pts received 0.2 or 0.3 mg/kg Rova-T IV on Day 1 of a 6-week cycle for 2 cycles. Objective was to evaluate safety, tolerability, PK, and preliminary efficacy and expression of DLL3. Antitumor activity was measured by RECISTv1.1, and DOR, PFS, OS were evaluated. Results: 29 pts were treated with Rova-T (6 at 0.2mg/kg, 23 at 0.3 mg/kg). Median age 68 yrs; 76% male; 64% DLL3 high (≥75% expression); 86% DLL3 positive (≥25%). 20 pts (69%) had received ≥3 prior lines of therapy. Similar PK and AEs were seen compared to previous studies in non-Japanese pts. The most frequently reported study drug-related AEs were platelet count decreased, pleural effusion, oedema peripheral, and aspartate aminotransferase increased, the majority Grade 1/2. No DLTs occurred, and both dose levels were tolerated. Three pts previously treated with ≥3 prior lines of therapy had confirmed partial response by investigator (10% of all pts; 17% of DLL3 high pts). For DLL3 high pts, mDOR was 3.0 mos (95% CI: 2.9, 4.1), mPFS was 2.9 mos (1.2-3.6), and mOS was 7.4 mos (4.1-11.9). Individual responses were analyzed in detail and radiographic data with tumor shrinkage will be shown. Conclusions: Rova-T demonstrated a manageable safety profile with promising preliminary efficacy in Japanese SCLC pts, in particular pts with DLL3 high expression. These data support further exploration of Rova-T treatment in Japanese pts with SCLC in global Phase 3 studies. Clinical trial information: NCT03086239.
Phase II study of S-1 in patients (pts) with previously treated Invasive thymoma (IT) and thymic carcinoma (TC): North Japan Lung Cancer Study Group Trial 1203.
Authors: Tsurumi Kyoji , Sugawara Shunichi , Kuyama Shoichi , Nakagawa Taku , Harada Daijiro , Tsukita Yoko , Tanaka Hisashi , Watanabe Kana , Mori Yoshiaki , Harada Toshiyuki , Hino Toshihiko , Fujii Masanori , Inoue Akira
Published: March 2020

8564

Background: Invasive thymoma and thymic carcinoma are rare epithelial neoplasms arise in the anterior mediastinum. Platinum-based chemotherapies are widely used for the first-line treatment for unresectable IT and TC. Although no standard treatment has been established for previously treated IT and TC, S-1 has demonstrated promising efficacy in some retrospective studies. Thus we conducted the first prospective multicenter phase II trial to evaluate the efficacy of S-1 for previously treated pts with advanced IT and TC. Methods: Eligible pts were aged 20 years or older with: advanced IT or TC not feasible to potentially curative treatments; disease progression after at least one regimen of platinum-based chemotherapy; Eastern Cooperative Oncology Group performance status 0-2; adequate organ function; written informed consent. Pts received S-1 orally, at a dose based on body surface area for 2 weeks in 3 weeks cycle until tumor progression or unacceptable toxicities. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile. Assuming that ORR of 25% in eligible pts would indicate potential usefulness while ORR of 10% would be the lower limit of interest, with alpha = 0.05 and beta = 0.2 according to a Simon’s two-stage design, the estimated accrual was 40 pts. Results: Between June 2012 and August 2018, 40 pts were enrolled and all pts were eligible (IT, n = 20; TC, n = 20). Median age was 64.5 years (range, 40-82), 75% (30/40) were male. Median treatment cycle was 5.5 (range, 1-82). ORR was 17.5% (95% CI: 7.3-32.8; IT, 10%, TC, 25%), and disease control rate was 85% (IT, 95%, TC, 75%). With a median follow-up of 51.9 months, median PFS was 7.0 months (IT, 11.3 months; TC, 5.4 months), and median OS was 40.3 months (IT, 58.5 months; TC, 22.7 months). The major grade 3-4 toxicities were anorexia (10%) and pneumonitis (5%). No treatment-related death was observed. Conclusions: Although the primary endpoint was unmet, S-1 monotherapy showed the moderate effects and could be available option especially for previously treated advanced TC. Clinical trial information: 000008174.
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]