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Myung-Ju Ahn



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    MA08 - Clinical Trials in Brain Metastases (ID 906)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
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      MA08.08 - Discussant - MA 08.05, MA 08.07 (ID 14601)

      15:55 - 16:10  |  Presenting Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
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      MA26.09 - Lazertinib, a Third Generation EGFR-TKI, in Patients with EGFR-TKI-Resistant NSCLC: Updated Results of a Phase I/II Study (ID 12817)

      14:30 - 14:35  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Background

      Lazertinib (YH25448) is a highly mutant-selective, irreversible 3rd-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that can penetrate the blood-brain barrier, and targets the activating EGFR mutations Del19 and L858R, as well as the T790M mutation, while sparing wild type. We report the updated results from a Phase I/II study of lazertinib (NCT03046992)

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced and metastatic NSCLC who had progressed after treatment with EGFR-TKIs with/without asymptomatic brain metastases (BM) were enrolled in an open-label, multicenter, phase I/II study with dose-escalation and expansion cohorts. Lazertinib was administered once daily at doses between 20 to 320 mg in a 21-day cycle. Patients were assessed for safety, tolerability, pharmacokinetics and efficacy. T790M status was confirmed in the dose-expansion cohorts.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 115 patients (median age 62 years, female 62%) were enrolled. The dose-escalation cohort included 38 patients administered with 20 to 320 mg across 7 dose levels, and 77 patients in the dose-expansion cohort were administered with 40 to 240 mg across 5 dose levels. No dose-limiting toxicities were observed in the dose-escalation cohort. Systemic exposure increased dose-dependently. Of the evaluable patients (n=110) at data cut-off, the objective response rate (ORR) was 65% (95% confidence interval [CI], 54.9 to 73.4). The ORR for 93 of the T790M+ patients was 69% (95% CI, 58.4 to 78.0). In patients with BM (n=12), the intracranial ORR was 50% (95% CI, 21.1 to 78.9). The most common treatment-emergent adverse events (TEAEs) were pruritus (19%), decreased appetite (17%), rash (14%), and constipation (12%). The most frequently reported TEAEs of grade ≥ 3 were hyponatraemia (2%), nausea (2%) and pneumonia (2%).

      ORR in T790M+ patients
      Dose QD 20 mg 40 mg 80 mg 120 mg 160 mg 240 mg
      Evaluable patients*, n 2 25 18 22 18 8
      ORR, n (%) 2 (100) 17 (68) 11 (61) 17 (77) 11 (61) 6 (75)
      * Patients were deemed evaluable for response if they underwent a post-baseline radiological assessment (RECIST 1.1) or were discontinued prior to the post-baseline assessment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lazertinib was safe, well-tolerated and exhibited promising systemic and intracranial antitumor activity in EGFR T790M+ NSCLC patients. The dose-expansion cohort as the first and second-line setting has been initiated from April 2018.

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    MS28 - IO Combinations in Advanced NSCLC (ID 806)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 106
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      MS28.02 - Combination IO+IO (ID 11521)

      13:45 - 14:00  |  Presenting Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    OA02 - Novel Therapies in ROS1, HER2 and EGFR (ID 893)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 105
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      OA02.01 - Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) (ID 13903)

      10:30 - 10:40  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Background

      Entrectinib is a central nervous system (CNS) active, potent, and selective inhibitor of ROS1, TRKA/B/C and ALK. Entrectinib is more potent against ROS1 than crizotinib, the only agent currently approved for the treatment of ROS1-positive NSCLC. Interim data demonstrated that entrectinib was tolerable and achieved high objective response rates (ORR) in patients with ROS1-positive, ROS1 inhibitor-naive NSCLC, including patients with baseline CNS disease (Ahn MJ WCLC 2017).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Phase 1/2 studies of entrectinib (ALKA, STARTRK-1, STARTRK-2; EudraCT 2012-000148-88; NCT02097810; NCT02568267) enrolled patients with locally advanced or metastatic solid tumors. The safety-evaluable population included patients who received ≥1 dose of entrectinib. The integrated efficacy analysis included ROS1-positive NSCLC patients enrolled based on identification of ROS1 fusions via nucleic acid-based diagnostic platforms. Safety was assessed by monitoring adverse events (AEs), laboratory tests, and physical examination. Tumor assessments were performed at the end of cycle 1 and every 8 weeks thereafter. All scans were submitted for blinded independent central review (BICR) using RECISTv1.1. Primary endpoints were ORR and duration of response (DOR) by BICR. Key secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Additional endpoints evaluated in patients with baseline CNS disease were intracranial ORR (defined as complete or partial responses in patients with baseline CNS lesions per BICR using RECISTv1.1), intracranial DOR, and PFS. For intracranial assessments, the CNS subgroup was derived per BICR; for systemic analyses, the CNS subgroup was derived per investigator.

      4c3880bb027f159e801041b1021e88e8 Result

      There were 53 efficacy-evaluable patients with treatment-naïve, ROS1-positive NSCLC. BICR ORR was 77.4% (95% CI 63.8–87.7) with complete responses in three patients (5.7%); median BICR DOR was 24.6 months (95% CI 11.4–34.8). Per baseline CNS status (as determined by investigator), median BICR PFS was 26.3 months (95% CI 15.7–36.6) and 13.6 months (95% CI 4.5–NR) for patients without (n=30) and with CNS disease (n=23), respectively. Intracranial ORR was 55.0% (95% CI 31.5–76.9) and median intracranial DOR was 12.9 months (95% CI 5.6–not reached [NR]) in patients with baseline CNS disease per BICR (n=20). In the overall safety-evaluable population (n=355), most treatment-related AEs were grade 1–2. Few patients required dose reduction (27.3%) or discontinued treatment (3.9%) due to treatment-related AEs.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Entrectinib was tolerable with a manageable safety profile, and showed clinically meaningful, deep and durable systemic responses in ROS1-positive NSCLC. Clinically meaningful intracranial activity was also demonstrated in patients with baseline CNS disease.

      Study Sponsor: Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.

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      OA02.02 - Safety and Preliminary Clinical Activity of Ropotrectinib (TPX-0005), a ROS1/TRK/ALK Inhibitor, in Advanced ROS1 Fusion-Positive NSCLC (ID 14217)

      10:40 - 10:50  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Background

      Ropotrectinib is a potent ROS1/TRK/ALK inhibitor with a >90-fold greater ROS1 potency than crizotinib. Preclinical studies demonstrate robust activity against all known ROS1 resistance mutations, including solvent-front mutation G2032R.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this Phase 1 study (NCT03093116), TKI-naïve and TKI-refractory (≥1 TKI) pts with advanced ALK/ROS1/TRK+ solid tumors received ropotrectinib. Asymptomatic brain metastases were allowed. Primary objectives were to determine MTD and RP2D, with safety, pharmacokinetics, and preliminary antitumor efficacy as the secondary objectives. This is a safety analysis of all pts and subgroup efficacy analysis of the ROS1+ NSCLC pts on the study.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 16-April-2018, 72 pts have been treated at 6 dose levels from 40mg QD to 200mg BID. Most AEs were grade 1-2. Common (>10%) treatment-related AEs included dizziness (49%), dysgeusia (46%), paresthesias (29%), constipation (19%), fatigue (18%), nausea (11%), and anemia (11%). 4 DLTs were observed at ≥240mg/day: 1 grade 3 (Gr3) dyspnea/hypoxia, 2 Gr3 & 1 Gr2 dizziness. 31 of 72 pts had ROS1+ NSCLC by local testing (FISH, n=20; NGS, n=11) with 1 pt determined as ROS1-negative by central NGS. Antitumor activity in ROS1+ NSCLC has been observed at ROS1 dose levels 40mg QD-160mg BID per investigator assessment, with the best ORR 70% for TKI-naïve and 11% for TKI-refractory pts (17% for 1 prior TKI crizotinib, n=12) (Table). Two crizotinib-resistant pts with G2032R achieved durable cPR and cSD, respectively. Ongoing blinded independent review identified 7 evaluable pts with target CNS lesions at baseline; the intracranial best ORR was 43% (3 cPR, 1 PR*). Updated efficacy data and ctDNA biomarker analyses will be presented.

      Dose Level

      TKI Naïve (n = 10)

      TKI Refractory (n = 20)

      n

      Best Overall Response

      n

      Best Overall Response

      40 mg QD (n = 6)

      2

      2 cPR (ORR 100%)

      4

      2 cSD, 1 SD, 1 PD

      80 mg QD (n = 5)

      2

      2 cPR (ORR 100%)

      3

      1 cSD, 2 SD

      160 mg QD (n = 10)

      4

      2 cPR, 2 cSD (ORR 50%)

      6

      2 cPR, 2 cSD, 1 SD, 1 PD (ORR 33%)

      240 mg QD (n = 2)

      1

      1 cPR (ORR 100%)

      1

      1 SD

      160 mg BID (n = 7)

      1

      1 PR*

      6

      1 PR*, 1 SD*, 1 cSD, 2 SD, 1 NE

      Total (n = 30)

      10

      7 cPR, 1 PR*, 2 cSD

      20

      2 cPR, 1 PR*, 6 cSD, 1 SD*, 7 SD, 2 PD, 1 NE

      Best ORR

      70%

      11%

      Median follow-up

      8 months with 90% still on treatment

      4 months with 50% still on treatment

      cPR: confirmed partial response; SD: stable disease for 2 cycles; cSD: SD for at least 4 cycles; PR* or SD*: waiting for subsequent time point scan; PD: progressive disease; NE: inevaluable; ORR: objective response rate

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ropotrectinib is well tolerated and demonstrates promising activity in pts with advanced ROS1+ NSCLC, including TKI-naïve and TKI-refractory pts. RP2D has not yet been achieved. These Phase 1 data warrant further clinical testing of ropotrectinib in ROS1+ NSCLC.

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    OA10 - Right Patient, Right Target & Right Drug - Novel Treatments and Research Partnerships (ID 910)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 106
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      OA10.05 - An Open-Label, Multicenter, Phase II Single Arm Trial of Osimertinib in NSCLC Patients with Uncommon EGFR Mutation(KCSG-LU15-09) (ID 14365)

      11:15 - 11:25  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Background

      Approximately 10% of EGFR mutants harbor uncommon mutations, which represent a heterogeneous group of rare molecular alterations within exons 18-21 and the sensitivity to EGFR TKIs is variable. Osimertinib is a potent irreversible inhibitor of both sensitizing EGFR mutation and T790M. In preclinical data, osimertinib was found to be active against most uncommon EGFR mutants, apart from the exon 20 insertion variant. Here we present the efficacy and safety of osimertinib in patients with uncommon EGFR mutation positive NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with histologically confirmed metastatic or recurrent NSCLC with activating EGFR mutation other than exon 19 deletion, L858R, T790M and insertion in exon 20 were eligible. Patients received 80mg of osimertinib orally, once daily until progression or unacceptable toxicity. Response was assessed every 8 weeks by investigator. The trial was registered with ClinicalTrials.gov, number NCT03424759.

      4c3880bb027f159e801041b1021e88e8 Result

      Between Mar 2016 and Oct 2017, 35 patients were enrolled. Median age was 59, 63% male, 43% never smoker, 97% adenocarcinoma. 63% of patients were treated as first-line therapy. The mutations identified were G719A/C/D/S/X (19, 54.3%) followed by L861Q (9, 25.7%), S7681 (8, 22.9%), and others (3, 8.6%). The overall response rate was 50.0% (95% CI 32.8-67.2) and DCR was 88.9% (95% CI 78.1-99.7). Seven patients (77.8%) with L861Q mutation achieved partial response; 10/19 (52.6%) with G719A/C/D/S/X mutation; 3/8 (37.5%) with S768I mutation. At data cutoff (Apr, 2018), the median PFS was 8.2 months (95% CI 1.9- 14.4) and median duration of response was 9.8 months (95% CI 7.6-12.0). The most common adverse events were rash (n=11, 31.4%), anorexia (n=8, 22.9%), and diarrhea (n=7, 20.0%). Grade 3 or 4 AEs were reported in 8 of 35 patients (23%), but all of AEs were manageable.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Osimertinib showed highly active in NSCLC patients harboring uncommon EGFR mutation with manageable safety profile, consistent with previous reports. Further analysis will be provided.

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      OA10.06 - A First-in-Human Phase 1 Trial of the EGFR-cMET Bispecific Antibody JNJ-61186372 in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 13006)

      11:25 - 11:35  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Background

      JNJ-61186372 (JNJ-372) is a bispecific antibody targeting both EGFR and cMET. In preclinical studies, JNJ-372 demonstrated efficacy in EGFR and cMET driven tumor xenograft models (including EGFR T790M and MET-amplified/HGF secretion), consistent with inhibition of ligand binding, receptor degradation, and ADCC activity. The goal of Part 1 of this study (reported here) was to assess the safety, pharmacokinetics (PK), and preliminary efficacy of JNJ-372 and to identify the recommended phase 2 dose(s) to be explored in Part 2.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with previously treated, advanced NSCLC were enrolled at two sites and treated with escalating doses of JNJ-372 administered IV weekly for the first 4-week cycle, then biweekly for each subsequent cycle. PK sampling was taken at multiple time points within cycle 1 and 2. Disease assessments were performed every 8 weeks. Tumors were characterized at baseline through next-generation sequencing of circulating tumor DNA (Guardant 360).

      4c3880bb027f159e801041b1021e88e8 Result

      25 patients were treated with JNJ-372 during dose escalation: 140mg (n=3), 350mg (n=3), 700mg (n=9), 1050mg (n=7), 1400mg (n=3). Median age was 63y, 48% were male, 100% were Asian, 84%/12%/4% had adenocarcinoma/squamous/other histology, and median prior therapies was 4. No dose-limiting toxicities were observed at any dose level tested. The most frequent treatment-emergent AEs were infusion-related reactions (76%), rash/acneiform dermatitis (40%), dyspnea (24%), paronychia (24%), pruritus (20%), fatigue (20%), and nausea (20%); incidence of peripheral edema (cMET-related toxicity) was 12%. Infusion-related reactions were grade ≤2 severity, observed primarily with the first dose. The worst severity of rash/acneiform dermatitis was grade 2 (16%). One treatment-related AE of grade ≥3 severity was reported (neutropenia grade 3, possibly related). JNJ-372 demonstrated linear PK at dose levels 350 mg and above with non-linear PK at lower concentrations, suggesting target-mediated drug disposition. Doses ≥700mg resulted in average steady-state concentrations at or above the preclinically established therapeutic target level. Preliminary evidence of efficacy (maximum change from baseline in sum of target lesion diameters) was observed in a patient with squamous cell carcinoma (-20%), a patient with wtEGFR adenocarcinoma (-20%), and 4 patients with EGFR-mutant adenocarcinoma (≥-30%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      JNJ-372 is a novel EGFR-cMET bispecific antibody. The manageable safety profile and preliminary evidence of clinical activity support active accrual of patients with previously treated EGFR-mutant NSCLC. The first recommended dose of 1050mg is being evaluated in Part 2.

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-01 - ROS1-Positive Non-Small Cell Lung Cancer: Real-World Data in Korea (ID 11799)

      16:45 - 18:00  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Slides

      Background

      ROS1 rearranged non-small cell lung cancer (NSCLC) is classified as a distinct molecular subset with a therapeutically druggable target. ROS1 rearrangement is most often identified in never-smoker with adenocarcinoma and EGFR and ALK wild type patients. Treatment with tyrosine kinase inhibitors (TKIs) which target the ROS1 kinase domain is considered standard of care for the ROS1-positve NSCLC, by showing a robust and durable response. However, information regarding the clinical characteristics and the outcomes of TKI treatment in the real world remains limited.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We have identified 103 consecutive cases of ROS1-positive NSCLC from January 2001 to February 2018 by break apart fluorescence in situ hybridization (FISH) (n=84), next-generation sequencing (n=23) or both (n=3). Information on fusion breakpoints was available for 8 patients. Clinical data including patient characteristics, incidence of brain metastasis, and response to chemotherapy or TKI were retrospectively analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      The median age was 56 years, 58.9% of patients were female, and 75.7% were never smokers. Adenocarcinoma was predominant (98.1%), and 2 cases with pleomorphic carcinoma were identified. Sixty percent of patients had an extra-thorax metastatic lesion, and 22% had intracranial lesion at the initial presentation or at the time of recurrence. Median time to brain metastases was 12.0 months (range 2.1 to 84.1). Majority of the patients received palliative chemotherapy (93.2%), and 7.8% of patients received definite concurrent chemoradiotherapy. Most common fusion partner was CD74 followed by SDC4, EZR, TPM3, TFG, ZCCHC8, SLMAP, and MYO5C, all of which had preserved tyrosine kinase domain of ROS1. There were no clinical correlations between different fusion partners and TKI treatment outcomes. The median overall survival for the study population was 52.1 months (95% confidential interval [CI] 23.6 – not reached). For 90 patients treated with pemetrexed-based chemotherapy, the overall response rate (ORR) and progression-free survival (PFS) was 53.3% and 8.0 months (95% CI 6.4 – 11.7), respectively. The ORR and PFS was 70.7% and 12.7 months (95% CI 8.1 – 21.8) for 50 patients treated with TKI. Brain metastasis was more commonly observed during the TKI treatment (15.5%) than pemetrexed-based chemotherapy (6.7%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      ROS1-positive NSCLC has distinct clinical characteristics with high and durable response to both TKI and pemetrexed-based chemotherapy. Given its novel characteristics and distinct clinical responses to conventional chemotherapies and TKIs, the treatment strategy for ROS1-positive NSCLC remains to be further developed.

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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-03 - Suppressive Immune Cell Profiling in Patients with Non-Small Cell Lung Cancer. (ID 12878)

      16:45 - 18:00  |  Author(s): Myung-Ju Ahn

      • Abstract

      Background

      The factors in tumor microenvironment hinder T cell activities against tumor cells. The major immunosuppressive cells in tumor sites are myeloid derived suppressor cell (MDSC), tumor associated macrophage (TAM), and regulatory T (Treg) cell, and the effector molecules released by those immunosuppressive cells also regulate T cell activities. Therefore, in this study we examined the pattern of immunosuppressive cells in patients with non-small cell lung cancer depending on their stages and we compared those immunosuppressive cells in healthy donor blood PBMC as well. Then, we tested T cell activities to verify whether suppressive immune cell populations can influence T cell activity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Granulocytic-MDSC, Monocytic-MDSC, TAM, and Treg population from patients’ PBMC (n=59) and healthy donors’ PBMC (n=20) were analyzed by FACS Verse with appropriate antibodies. For suppressive assay, isolated T cells were activated with anti-CD3 and anti-CD28 for an hour and then MDSC was co-cultured with T cells for a week followed by Ki-67 level analysis by FACS Verse. T cell activity and suppression were tested by FACS analysis with identified cell surface markers.

      4c3880bb027f159e801041b1021e88e8 Result

      G-MDSC (p-value=0.0023) and M-MDSC (p-value=0.0032) population were higher in advanced non-small cell lung cancer patients (stage III&IV) compared with stage I&II patients or healthy donor. G-MDSC isolated from patient’s blood was co-cultured with activated T cells from the same patient. After one week, T cell activity was dramatically inhibited compared with T cell alone (p < 0.001, E:T = 5:1, 10:1) confirming suppressive activity of MDSC against T cells. TAM population was increased as disease progressed (p<0.001), and Treg also slightly increased (p-value=0.0373) in stage III&IV. Activated T cells were higher in stage III&IV, but suppressed T cells were also higher in stage III&IV compared with stage I&II.

      8eea62084ca7e541d918e823422bd82e Conclusion

      G-MDSC and M-MDSC population increased as disease progressed and G-MDSC effectively suppressed T cell activities. TAM population increased in advanced non-small cell lung cancer patients, and Treg population also slightly increased in stage III&IV. Both activated and suppressed T cells were higher in stage III&IV compared with stage I&II.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-10 - Prognostic Impact of Longitudinal Monitoring of Radiomic Features in Patients with Advanced Non-Small Cell Lung Cancer (ID 12877)

      16:45 - 18:00  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Slides

      Background

      Tumor growth dynamics varies substantially in non-small cell lung cancer (NSCLC). We aimed to develop novel biomarkers reflecting longitudinal change of radiomic features in NSCLC and evaluate prognostic power of those.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Fifty-three patients with advanced NSCLC included in this retrospective study. Measurable lesions on baseline and follow-up computed tomography (CT) were segmented and 23 radiomic features were extracted. All three variables reflecting patterns of longitudinal change were extracted: the area under the curve (AUC), beta value, and AUC2. We constructed models for predicting survival using multivariate cox regression, and identified the performance of these models.

      4c3880bb027f159e801041b1021e88e8 Result

      In volume, AUC2 showed an excellent correlation with pattern of longitudinal volume change (r = 0.848, p < 0.000), and showed a significant difference in overall survival time (p = 0.035). In multivariate regression analysis, kurtosis of positive pixel values (p < 0.000), and surface area (p = 0.001) on baseline CT, and AUC2 of density (p < 0.000), skewness of positive pixel values (p = 0.003), and entropy at inner (p = 0.001) were found to be associated with overall survival time, and the area under the receiver operating characteristics curves were 0.922, and 0.771 at 1 year, and 3 years of follow-up.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Longitudinal change of radiomic tumor features would be prognostic biomarkers in patients with advanced NSCLC.

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      P2.01-57 - Prognostic Implication of Clinical, Imaging, and Pathologic Parameters in N2(+) Stage IIIA Lung Cancer Patients (ID 13564)

      16:45 - 18:00  |  Author(s): Myung-Ju Ahn

      • Abstract

      Background

      As a comprehensive study of large scale and long-term clinical outcomes from a single institution, we are trying to analyze any predictive or prognostic factors for survival outcomes in N2(+) NSCLC patients. The purpose of this study is to investigate the efficacy of clinical, imaging (CT and PET-CT), and pathologic parameters, as a prognostic factor in N2(+) NSCLC patients undergoing tri-modality therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed 160 patients with N2(+) NSCLC patients between January 2008 and June 2014. All patients underwent preoperative concurrent chemoradiotherapy (CCRT) (44-45 Gy in 22-25 fractions concurrent with weekly DP chemotherapy) and surgery. Clinical, imaging (CT and PET-CT), and pathologic parameters were analyzed with respects to outcomes.

      4c3880bb027f159e801041b1021e88e8 Result

      Overall pathologic down-staging and pathologic complete response following preoperative CCRT were achieved in 66 (41.3%) and 13 patients (8.1%), respectively. The median follow-up durations of all patients was 43 months (2~106 months). The 5-year rates of disease-free survival (DFS) and overall survival (OS) were 33.3% and 53.0%, respectively. Pathologic N down-staging (HR 2.604; 95% CI 1.418-4.779; p value=0.002) was a significant factor for DFS. Histopathology (HR 0.475; 95% CI 0.242-0.930; p =0.030), GTV of nodal lesion(s) on pre-RT CT (HR 1.066; 95% CI 1.029-1.104; p <0.001), type of surgery (HR 2.985; 95% CI 1.114-7.997; p =0.030), and proportion of viable tumor on cross-section area (HR 0.986; 95% CI 0.973-0.999; p =0.034) were significant factors for OS. Neither tumor volume reduction rate (TVRR) nor SUVmax was significant for DFS or OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In patients with N2(+) NSCLC undergoing tri-modality therapy, we proved that none of the imaging parameters correlated with prognosis, except pretreatment nodal volume. We confirmed that patients with adenocarcinoma showed prominently improved survival and pathologic N down-staging was a most important pathologic parameter as a prognosticator.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.12-05 - SUKSES (Small Cell Lung Cancer Umbrella Korea Studies): A Phase II Biomarker-Driven Umbrella Study in Relapsed or Refractory SCLC (ID 12673)

      16:45 - 18:00  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Slides

      Background

      Although initial platinum-based treatment demonstrated high response rate (RR) in extensive stage SCLC, limited options are available for subsequent systemic therapy. Recent studies with comprehensive genomic profiling identified cell cycle-related gene alteration, such as TP53 and RB1 inactivation, and RICTOR amp as a major characteristic of SCLC. Based on this observation, we designed umbrella clinical trial based on the hypothesis that controlling cell cycle checkpoint, DNA damage repair mechanism, and mTOR pathway with small molecules and monoclonal antibodies targeting these pathways might be an effective approach for the later line SCLC treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      SUKSES trial (NCT02688894) is a phase 2 study with seven treatment arms. Four arms for the biomarker-positive population. Arm A (AKT1 mt); Arm B (BRCA1 or BRCA2 mt, ATM deficiency, MRE11A mt or other HR pathway gene mt); Arm C (MYC family protein amplification or CDKN2A mt either of which combined with TP53 mt); Arm D (RICTOR amp). Three arms for the biomarker-negative population. Arm-N1, N2, and N3.

      Pathologically confirmed SCLC patients are eligible for the molecular screening. For study participation, patients must have at least one measurable lesion after progression from first-line platinum-based therapy. Patients are enrolled in either second or third line based on their initial treatment response. Following treatment is applied after allocation: Arm-A (AZD5363); arm-B (Olaparib); arm-C (AZD1775); arm-D (AZD2014); arm-N1 (AZD1775); arm-N2 (Olaparib and AZD6738); arm-N3 (AZD2811). Primary endpoint for this study is objective RR. Duration of treatment, disease control rate at eight weeks, progression-free survival, exploratory biomarker will be evaluated as secondary endpoint.

      As of May 2018, 157 patients have been screened for the molecular profiling. Arm A was closed due to low discovery rate of AKT1 mutation. Of the planned 28 patients for each biomarker positive arm, 9 for arm B, 7 for arm C and 4 for arm D have enrolled. For the negative-biomarker arms, 24 out of 45 patients are recruited for arm N1 and 9 patients for Arm N3. Arm N2 is under review by Institutional Review Board.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-18 - Comparison of PD-L1 Immunohistochemical Assays and Clinical Response to Anti PD-1 Checkpoint Inhibitors in Patients with Lung Cancer (ID 14296)

      12:00 - 13:30  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Slides

      Background

      The anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors, nivolumab and pembrolizumab, are currently approved for the treatment of patients with NSCLC. The PD-L1 expression represents the most validated predictive marker of response to PD-1 inhibitors. However, there are several different immunohistochemical assays to assess the PD-L1 expression using different antibodies, platforms, and cutoff values. We compared the PD-L1 expression evaluated by IHC 22C3 PharmDx with that observed by Ventana SP263 and analyzed correlation with response to anti PD-1 inhibitors.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively analyzed 109 patients with lung cancer to be treated with anti PD-1 inhibitors who have PD-L1 expression levels obtained with both the 22C3 and SP263 assays. We reviewed medical records to obtain information about the patient’s clinical characteristics, response evaluation and survival data. The relationship between PD-L1 expression levels evaluated by the 22C3 and SP263 assays was calculated using the concordance correlation coefficient, Pearson’s precision analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      Most patients were male (70%), smoker (65%), ECOG PS 1 (73%), and histologically adenocarcinoma (55%) or squamous cell carcinoma (29%). 30% of patients had EGFR mutations. Patients were treated with pembrolizumab (n=41, 38%), or nivolumab (n=67, 61%). The median cycle of anti PD-1 checkpoint inhibitor was three (range, 1-25). There was moderate analytical correlation between 22C3 and SP263 PD-L1 levels. At the clinically relevant cutoffs ( < 10% vs. 10%; and <1% vs. 1-49% vs. 50%), the concordance correlation coefficient between 22C3 and SP263 were 0.68 (95%CI: 0.59-0.77) and 0.66 (95%CI: 0.51-0.81), respectively. The overall response rate (ORR) was 25.0% for all patients. The ORR was comparable regardless of the cutoff levels of PD-L1 expression by SP263 assays (ORR 39.6%, 41.7%, and 47.4% respectively for PD-L1 expression by 1%, 10%, 50% cutoff levels). But, the correlation between ORR and PD-L1 expression by 22C3 assays was not statistically significant. At 1% cutoff value, progression free survival was longer in patients with high vs. low tumor PD-L1 expression (2.8 months vs. 1.2 months, HR 0.63, 95%CI: 0.41-0.97, p=0.03) by the 22C3 and (3.1 months vs. 1.3 months, HR 0.61, 95% CI:0.40-0.93, p=0.02) by the SP263, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We showed a moderate correlation between PD-L1 expression data obtained with the 22C3 and SP263 assays. These two assays could be used interchangeably and might be helpful for decision with anti PD-1 checkpoint inhibitors. Further analysis will be updated.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.16-41 - Postoperative Pembrolizumab for the Patients with Pathologic Stage I Adenocarcinoma with Solid or Micropapillary Pattern (ID 14418)

      12:00 - 13:30  |  Author(s): Myung-Ju Ahn

      • Abstract

      Background

      Prognosis of surgically resected stage I adenocarcinoma was relatively fair with up to 75% of 5 year disease free survival rate. However, in some cases, in spite of the very small-sized tumor, recurrence as systemic metastasis is found. Solid or micropapillary subtype adenocarcinoma are reported as poor prognostic subtypes, additional treatment after surgical resection for those subgroup was required to improve survival. We reported that incidence of PD-L1 strong positivity is significantly higher in solid-predominant subtype of adenocarcinoma, PD-L1 inhibitor can be more effective adjuvant treatment modality in those subtype.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Design: Open-label, single arm, single center, phase 2 trial. (NCT03254004)

      Eligibility: The subject must have primary lung adenocarcinoma with stage I and less than 4 centimeter, whose tumor should be solid-predominant or micropapillary (>5%) by postsurgical pathological examination.

      Objective: The primary objective of this study is to assess the improvement of disease-free survival rate by adjuvant therapy with pembrolizumab for solid or micropapillary adenocarcinoma with pathologic stage I and tumor size less than 4 cm. The secondary objective is to assess the safety profile of adjuvant pembrolizumab in adjuvant setting.

      Treatment: Pembrolizumab 20mg IV infusion every 3 weeks for 12 months until disease progression or prohibitive toxicity. The treatment should be started within 8 weeks after surgery.

      Statistics: The hypothesis is that adjuvant pembrolizumab will improve 3-year disease-free survival from 65% to 80% in pathologic stage Ia lung adenocarcinoma patients with solid/micropapillary subtypes. Assuming that the subject enrollment period is 1.5 years, follow-up of last registered subject period is 4 years, and the disease free survival period follows the exponential distribution, a significance level 5% (one side) and 63 peoples are required 85% at the power of test. At this time, assuming that the dropout rate is 10%, it is necessary to register 70 subjects

      Assessment : Chest CT (covering up to both adrenals) will be done every 3 months till 1 year since the study treatment, and then every 4 months afterward till 2 years and thereafter every 6 months till 3 years. Brain MRI and bone scan will be done at 1 year and 2 years since the study treatment. This study is an investigator-initiated trial with support from MSD.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)

    • Event: WCLC 2018
    • Type: Plenary Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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      PL02.03 - Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) (ID 11155)

      08:30 - 08:40  |  Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Background

      Brigatinib has robust efficacy in crizotinib-resistant ALK+ NSCLC, exhibiting median progression-free survival (mPFS) of 16.7 months. We report results of the first interim analysis from the ALTA-1L study of brigatinib vs crizotinib in ALK TKI-naive, ALK+ NSCLC (NCT02737501).

      This open-label, multicenter study enrolled patients with stage IIIB/IV ALK+ NSCLC based on local ALK testing (FDA approved/other). Eligible patients had ECOG PS 0–2, ≤1 prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor. Asymptomatic CNS metastases were allowed. All patients had systematic CNS imaging. Patients were randomized 1:1 to brigatinib 180 mg QD with 7-day lead-in at 90 mg or crizotinib 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). Interim analyses were planned at 50% and 75% of planned PFS events (n=198).

      275 patients were randomized (brigatinib/crizotinib, n=137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cut-off (19 February 2018), median follow-up brigatinib/crizotinib: 11.0/9.25 months; with 99 PFS events, brigatinib met the prespecified threshold for statistical superiority vs crizotinib in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33–0.74, log-rank P=0.0007); brigatinib mPFS was not reached (95% CI NR–NR) vs crizotinib 9.8 months (95% CI 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30–0.68), log-rank P=0.0001. Table shows additional efficacy data. Most common treatment-emergent AEs grade ≥3: brigatinib: increased CPK (16.2%), increased lipase (13.2%), hypertension (9.6%); crizotinib: increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis: brigatinib, 3.7%; crizotinib, 2.2%. Discontinuations due to AE (brigatinib/crizotinib): 11.8%/8.8%.

      Brigatinib showed a statistically and clinically significant improvement in PFS compared with crizotinib in ALK inhibitor–naive ALK+ NSCLC.

      BIRC-Assessed Endpoint, %

      Brigatinib

      (n=137)

      Crizotinib

      (n=138)

      P-Value
      All patients
      ORRa 76 (68–83b) 73 (65–80b)
      Confirmed ORR 71 (62–78b) 60 (51–68b) 0.0678
      With any intracranial CNS metastases
      (n=43) (n=47)
      iORRa 79 (64–90b) 23 (12–38b)
      Confirmed iORR 67 (51–81b) 17 (8–31b) <0.0001
      Median iPFS, months NR (11–NRb) 6 (4–9b)
      1-year iPFS 67 (47–80b) 21 (6–42b)
      HR 0.27 (0.13–0.54) <0.0001c
      With measurable intracranial CNS metastases
      (n=18) (n=21)
      iORRa 83 (59–96b) 33 (15–57b)
      Confirmed iORR 78 (52–94b) 29 (11–52b) 0.0028
      aResponse, ≥1 assessment; b95% CI; cLog-rank.

      a9ded1e5ce5d75814730bb4caaf49419

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