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D..R. Camidge

Moderator of

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    ISS01 - Industry Supported Symposium: Current and Emerging Treatments for Patients with ALK+ NSCLC – ARIAD Pharmaceuticals Inc. (ID 435)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 5
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      ISS01.01 - Welcome & Introduction (ID 7135)

      C. Zielinski, D..R. Camidge

      • Abstract

      Abstract not provided

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      ISS01.02 - ALK Inhibitors: Current Treatments and Sequencing (ID 7136)

      C. Zielinski

      • Abstract

      Abstract not provided

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      ISS01.03 - The Future of ALK Inhibitors: How the Treatment Paradigm May Change (ID 7137)

      D..R. Camidge

      • Abstract

      Abstract not provided

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      ISS01.04 - Will Mutation Testing be Standard in the Resistant Setting? (ID 7138)

      P. Jänne

      • Abstract

      Abstract not provided

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      ISS01.05 - Summary and Conclusions (ID 7139)

      C. Zielinski, D..R. Camidge

      • Abstract

      Abstract not provided



Author of

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    ISS01 - Industry Supported Symposium: Current and Emerging Treatments for Patients with ALK+ NSCLC – ARIAD Pharmaceuticals Inc. (ID 435)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 3
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      ISS01.01 - Welcome & Introduction (ID 7135)

      D..R. Camidge

      • Abstract

      Abstract not provided

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      ISS01.03 - The Future of ALK Inhibitors: How the Treatment Paradigm May Change (ID 7137)

      D..R. Camidge

      • Abstract

      Abstract not provided

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      ISS01.05 - Summary and Conclusions (ID 7139)

      D..R. Camidge

      • Abstract

      Abstract not provided

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    MA07 - ALK-ROS1 in Advanced NSCLC (ID 385)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 2
    • Now Available
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      MA07.01 - Updated Pooled Analysis of CNS Endpoints in Two Phase II Studies of Alectinib in ALK+ NSCLC (Now Available) (ID 5354)

      D..R. Camidge

      • Abstract
      • Presentation
      • Slides

      Background:
      Based on two single-arm, multicentre, phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]), the FDA approved the ALK inhibitor alectinib for use in ALK+ NSCLC patients after prior crizotinib. Alectinib was well tolerated in both phase II studies and showed efficacy against both systemic and central nervous system (CNS) disease, the latter being a common progression site in ALK+ NSCLC. This analysis uses pooled data from the latest cut-offs (22 Jan 2016 for NP28761; 1 Feb 2016 for NP28673) to examine the long-term CNS efficacy of alectinib.

      Methods:
      Both studies enrolled crizotinib-refractory patients ≥18 years with ECOG PS 0–2 and locally advanced or metastatic ALK+ NSCLC (confirmed by FDA-approved test). CNS metastases were permitted if asymptomatic. Patients received 600mg oral alectinib BID. The primary endpoint in both studies was objective response rate (ORR) by independent review committee; secondary CNS endpoints included CNS ORR, CNS duration of response (DoR), and CNS disease control rate (DCR). CNS response and progression were determined by RECIST v1.1. All patients had baseline imaging to assess CNS metastases, with further imaging every 6 or 8 weeks for NP28761 and NP28673, respectively.

      Results:
      The overall pooled analysis population comprised 225 patients (n=87 from NP28761; n=138 from NP28673); median follow-up for this updated analysis was 18.8 (0.6–29.7) months (>6 months additional follow-up). At baseline, 50 patients had measurable and 86 had non-measurable CNS disease; together, these groups comprised 136 patients, 60% of the overall pooled population. Seventy percent of patients had prior CNS radiotherapy; 58% of these completed radiotherapy >6 months before study entry. Updated CNS data are shown in the Table and are consistent with systemic results.

      Measurable CNS disease at baseline (n=50) Measurable and non-measurable CNS disease at baseline (n=136)
      CNS ORR, n (%) [95% CI] 32 (64.0) [49.2–77.1] 60* (44.1) [35.6–52.9]
      Complete response (CR), n (%) 11 (22.0) 39* (28.7)
      CNS DCR, n (%) [95% CI] 45 (90.0) [78.2–96.7] 117 (86.0) [79.1–91.4]
      Median CNS DoR, months [95% CI] Patients with event, n (%) 11.1 [7.6–NE] 18 (56.3) 13.8 [11.0–21.5] 32 (53.3)
      * N.B. Non-measurable disease response can only be classified as CR, non-CR/non-progressive disease (PD) or PD


      Conclusion:
      This updated pooled analysis with mature data confirms that alectinib can provide long-term control of CNS metastases in ALK+ NSCLC, with a high CR rate.

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      MA07.02 - Updated Efficacy and Safety Data from the Phase 2 NP28761 Study of Alectinib in ALK-Positive Non-Small-Cell Lung Cancer (Now Available) (ID 4918)

      D..R. Camidge

      • Abstract
      • Presentation
      • Slides

      Background:
      Alectinib, a CNS-active and highly selective ALK inhibitor, has efficacy in patients with ALK-positive NSCLC with and without previous crizotinib treatment. Updated efficacy and safety from the alectinib phase 2 North American NP28761 study (NCT01871805) of patients with ALK-positive NSCLC previously treated with crizotinib, with 15 months’ additional follow-up from the primary analysis and 9 months’ additional follow-up from the previous analysis are presented.

      Methods:
      Patients ≥18 years old with ALK-positive NSCLC (FDA-approved FISH test), disease progression following crizotinib, and ECOG PS ≤2 were enrolled. Patients received oral alectinib (600mg) twice daily until progression, death or withdrawal. Primary endpoint: overall response rate (ORR) by independent review committee (IRC; RECIST v1.1.) Secondary endpoints: investigator-assessed ORR; progression-free survival (PFS); overall survival (OS), CNS ORR (CORR); disease control rate (DCR); safety.

      Results:
      At the updated cut-off (22 January 2016) an additional 15 months' follow-up from the primary analysis, 87 patients were enrolled. Median follow-up: 17.0 months (range 1.1–28.6). ORR in the response evaluable population (REP; n=67) by IRC: 52.2% (95% CI 39.7–64.6), median duration of response: 14.9 months. Median PFS and OS: 8.0 and 22.7 months, respectively. Table 1 presents other efficacy endpoints. Grade ≥3 AEs were reported in 41% of the safety population (n=87); most common: elevated levels of blood creatine phosphokinase (8%), alanine aminotransferase (6%), aspartate aminotransferase (5%). Two patients withdrew due to AEs; 28% had AEs leading to dose modification/interruption. Mean dose intensity was 92.0%.

      IRC REP Responders, n CR, n (%) PR, n (%) SD, n (%) PD, n (%) Missing/NE, n (%) DCR, % (95% CI) n=67[*] 35 0 (0) 35 (52.2) 18 (26.9) 11 (16.4) 3 (4.5) 79.1 (67.4,88.1)
      Investigator REP Responders, n ORR, % (95% CI) n=87 [46[†]] 52.9 (41.9, 63.7)
      Measurable baseline CNS lesions (IRC)‖ Responders, n CORR, % (95% CI) Measurable/non-measurable baseline CNS lesions (IRC) Responders CORR,[‖] % (95% CI) n=16 12[‡] 75.0 (47.6, 92.7) n=52 21[§] 40.4 (27.0, 54.9)
      *n=20 did not have measurable disease per IRC and were not included in the IRC REP; [†]2 CR;[ ‡]4 CR;[ §]13 CR; [‖]non-measurable disease classified as CR, non-CR/non-PD or PD; NE=not evaluable/estimable

      Conclusion:
      Alectinib demonstrated durable responses, encouraging OS findings, good tolerability and an acceptable safety profile consistent with previous reports in this update of the NP28761 study with extended follow-up.

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    MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA08.01 - A Highly Sensitive Next-Generation Sequencing Platform for Detection of NSCLC EGFR T790M Mutation in Urine and Plasma (Now Available) (ID 4637)

      D..R. Camidge

      • Abstract
      • Presentation
      • Slides

      Background:
      Non-invasive genotyping of NSCLC patients by circulating tumor (ct)DNA is a promising alternative to tissue biopsies. However, ctDNA EGFR analysis remains challenging in patients with intrathoracic disease, with a reported 26-57% T790M mutation detection rate in plasma (Karlovich et al., Clin Cancer Res 2016; Wakelee et al., ASCO 2016). We investigated whether a mutation enrichment NGS could improve mutation detection in plasma and urine from TIGER-X, a phase 1/2 study of rociletinib in patients with EGFR mutation-positive advanced NSCLC.

      Methods:
      The therascreen (Qiagen) or cobas (Roche) EGFR test was used for EGFR T790M analysis in tumor biopsies. Urine and plasma were analyzed by trovera mutation enrichment NGS assay (Trovagene).

      Results:
      Of 174 matched tissue, plasma and urine specimens, 145 (83.3%) were T790M+ by central tissue testing, 142 (81.6%) were T790M+ by plasma, and 139 (79.9%) were T790M+ by urine. Urine and plasma combined identified 165 cases (94.8%) as T790M+. Of 25 cases positive by ctDNA but negative/inadequate by tissue, 16 were double-positive in plasma and urine, unlikely to be false positive (Figure 1). T790M detection rate was higher for extrathoracic (n=119) vs intrathoracic (n=55) disease in plasma (87.4% vs 69.1%, p=0.006) but not urine (81.5% vs 76.4%, p=0.42). Combination of urine and plasma identified T790M in 92.7% of intrathoracic and 95.8% of extrathoracic cases (p=0.47). In T790M+ patients, objective response rate was similar whether T790M mutation was identified by tissue, plasma or urine: 37.4%, 33.1% and 36.6%, respectively. 4 of 9 patients T790M+ by urine but negative by tissue responded, and 2 of 8 patients T790M+ by plasma but negative by tissue responded.

      Conclusion:
      Mutation enrichment NGS testing by urine and plasma combined identified 94.8% of T790M+ cases. Combination of urine and plasma may be considered before tissue testing in EGFR TKI resistant NSCLC, including patients without extrathoracic metastases. Figure 1



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    MA16 - Novel Strategies in Targeted Therapy (ID 407)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 2
    • Now Available
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      MA16.03 - Global RET Registry (GLORY): Activity of RET-Directed Targeted Therapies in RET-Rearranged Lung Cancers (Now Available) (ID 4325)

      D..R. Camidge

      • Abstract
      • Presentation
      • Slides

      Background:
      GLORY is a global registry of patients with RET-rearranged non-small cell lung cancer (NSCLC). In order to complement ongoing prospective studies, the registry’s goal is to provide data on the efficacy of RET-directed targeted therapies administered outside the context of a clinical trial. We previously reported results from our first interim analysis (Gautschi, ASCO 2016). Following additional accrual into the registry, updated results are presented here, with a focus on an expanded efficacy analysis of various RET inhibitors.

      Methods:
      A global, multicenter network of thoracic oncologists identified patients with pathologically-confirmed NSCLC harboring a RET rearrangement. Molecular profiling was performed locally via RT-PCR, FISH, or next-generation sequencing. Anonymized data including clinical, pathologic, and molecular features were collected centrally and analyzed by an independent statistician. Response to RET tyrosine kinase inhibition (TKI) administered off-protocol was determined by RECIST1.1 (data cutoff date: April 15, 2016). In the subgroup of patients who received RET TKI therapy, the objectives were to determine overall response rate (ORR, primary objective), progression-free survival (PFS), and overall survival (OS).

      Results:
      165 patients with RET-rearranged NSCLC from 29 centers in Europe, Asia, and the USA were accrued. The median age was 61 years (range 28-89 years). The majority of patients were female (52%), never smokers (63%), with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent metastasic sites were lymph nodes (82%), bone (51%) and lung (32%). KIF5B-RET was the most commonly identified fusion (70%). 53 patients received at least one RET-TKI outside of a clinical protocol, including cabozantinib (21), vandetanib (11), sunitinib (10), sorafenib (2), alectinib (2), lenvatinib (2), nintedanib (2), ponatinib (2) and regorafenib (1). In patients who were evaluable for response (n=50), the ORR was 37% for cabozantinib, 18% for vandetanib, and 22% for sunitinib. Median PFS was 3.6, 2.9, and 2.2 months and median OS was 4.9, 10.2, and 6.8 months for cabozantinib, vandetanib, and sunitinib, respectively. Responses were also observed with nintedanib and lenvatinib. Among patients who received more than one TKI (n=10), 3 partial responses were achieved after prior treatment with a different TKI.

      Conclusion:
      RET inhibitors are active in individual patients with RET-rearranged NSCLC, however, novel therapeutic approaches are warranted with the hope of improving current clinical outcomes. GLORY remains the largest dataset of patients with RET-rearranged NSCLC, and continues to accrue patients.

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      MA16.09 - Antitumor Activity and Safety of Crizotinib in Patients with MET Exon 14-Altered Advanced Non-Small Cell Lung Cancer (Now Available) (ID 5162)

      D..R. Camidge

      • Abstract
      • Presentation
      • Slides

      Background:
      MET alterations leading to exon 14 skipping occur in ~4% of non-squamous non‑small cell lung cancer (NSCLCs) and 20–30% of sarcomatoid lung carcinomas, resulting in MET activation and sensitivity to MET inhibitors in vitro.[1–4] Crizotinib, initially developed as a MET inhibitor, is currently approved for the treatment of ALK-rearranged and ROS1-rearranged advanced NSCLC. We present crizotinib antitumor activity and safety data in patients (pts) with MET exon 14-altered advanced NSCLC.

      Methods:
      Advanced NSCLC pts positive for MET exon 14-alteration status determined locally by molecular profiling were enrolled into an expansion cohort of the ongoing phase I PROFILE 1001 study (NCT00585195) and received crizotinib at a starting dose of 250 mg BID. Objective responses were assessed using RECIST v1.0.

      Results:
      As of the data cut-off of Feb 01, 2016, 21 pts with MET exon 14-altered NSCLC received crizotinib treatment (18 response-evaluable, 3 not yet evaluable). Median age was 68 y (range: 53−87). Tumor histology was: 76% adenocarcinoma, 14% sarcomatoid adenocarcinoma, 5% adenosquamous carcinoma, and 5% squamous cell carcinoma. Sixty-two percent (62%) of pts were former-smokers, 38% never-smokers, and there were no current smokers. Duration of treatment ranged from 0.2 to 12.2 mo, with 76% of pts (16/21) still ongoing. Five pts discontinued treatment (1 due to AE, 3 due to clinical or disease progression, and 1 preferred alternative treatment formulation). PRs were observed in 8 pts, for an objective response rate of 44% (95% CI: 22–69); 9 pts had stable disease. Median time to response was 7.8 weeks (range: 7.0–16.3), which was the approximate time of the scheduled first on treatment tumor scans for patients. Median progression-free survival could not be calculated. The most common (≥25%) treatment-related AEs (TRAEs) were edema (43%) diarrhea (33%), nausea (33%), vision disorder (33%), and vomiting (29%). Most TRAEs were grade 1/2 in severity and consistent with the known safety profile of crizotinib. Four grade 3 TRAEs (edema, bradycardia, anemia, and weight increased) and no grade 4 or 5 TRAEs were reported. Enrollment of pts with MET exon 14-altered NSCLC continues, and updated data will be available at the time of presentation.

      Conclusion:
      Crizotinib has clinically meaningful antitumor activity in pts with MET exon 14-altered advanced NSCLC. The drug has a tolerable AE profile, consistent with that previously reported for pts with ALK-rearranged or ROS1-rearranged advanced NSCLC. Further study of crizotinib in this pt population is warranted.

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    OA08 - Targeted Therapies in Brain Metastases (ID 381)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      OA08.06 - Brigatinib Activity in Patients with ALK+ NSCLC and Intracranial CNS Metastases in Two Clinical Trials (Now Available) (ID 4374)

      D..R. Camidge

      • Abstract
      • Presentation
      • Slides

      Background:
      Patients treated with crizotinib often experience disease progression in the brain. Brigatinib, an investigational next-generation ALK inhibitor, is being evaluated in an ongoing phase 1/2 trial (Ph1/2) and an ongoing pivotal phase 2 trial (ALTA).

      Methods:
      In Ph1/2, patients with advanced malignancies, including ALK+ NSCLC, received 30–300 mg brigatinib per day. In ALTA, patients with crizotinib-resistant advanced ALK+ NSCLC received 90 mg qd (arm A) or 180 mg qd with a 7-day lead-in at 90 mg (arm B). Efficacy (in both trials) and safety (in ALTA) are reported for ALK+ NSCLC patients with brain metastases at baseline.

      Results:
      In Ph1/2 and ALTA, 50/79 (63%; IRC-assessed) and 154/222 (69%; investigator-assessed) of ALK+ NSCLC patients, respectively, had baseline brain metastases. In Ph1/2 (n=50), median age was 53 years, 76% received prior chemotherapy, and 8% were crizotinib-naive. In ALTA (n=154), median age was 52 years; 75% received prior chemotherapy. As of November 16, 2015, 25/50 (50%) patients were receiving brigatinib in Ph1/2; as of February 29, 2016, 101/154 (66%) patients were receiving brigatinib in ALTA. For patients with measurable lesions, confirmed iORR was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). Among patients with only nonmeasurable lesions (Ph1/2, n=31; ALTA A/B, n=54/n=55), 35% had confirmed complete resolution of lesions in Ph1/2; 7%/18% had confirmed complete resolution in ALTA A/B. For all evaluable patients with baseline brain metastases, median intracranial PFS was 15.6 months in Ph1/2 (n=46) and 15.6/12.8 months in ALTA A/B (n=80/n=73). Most common treatment-emergent adverse events in ALTA in patients with baseline brain metastases (n=151 treated): nausea (A/B, 32%/43%), headache (30%/30%), diarrhea (18%/36%), cough (21%/30%), vomiting (25%/26%); grade ≥3 (excluding neoplasm progression): increased blood CPK (1%/11%), hypertension (4%/7%), increased lipase (3%/3%), pneumonia (1%/4%).

      Conclusion:
      Brigatinib has demonstrated substantial clinical activity in ALK+ NSCLC patients with brain metastases in both Ph1/2 and ALTA.

      IRC-Assessed Confirmed Intracranial Response Rates for Patients With Measurable Brain Metastases at Baseline
      Any No rad/active[a]
      Ph1/2[b] n=15 n=9
      iORR 8(53) 6(67)
      iDCR 13(87) 8(89)
      ALTA[c]
      Arm A n=26 n=19
      iORR 11(42) 8(42)
      iDCR 22(85) 16(84)
      Arm B n=18 n=15
      iORR 12(67) 11(73)
      iDCR 15(83) 14(93)
      Data are n(%) iDCR=intracranial disease control rate iORR=intracranial objective response rate IRC=independent review committee [a]No prior brain radiotherapy (Ph1/2); active (untreated or treated and progressed) brain lesions (ALTA) [b]NCT01449461; last scan date: October 8, 2015 [c]NCT02094573; last scan date: April 14, 2016


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    OA16 - Improving the Quality of Lung Cancer Care - Patients Perspective (ID 399)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Patient Support and Advocacy Groups
    • Presentations: 1
    • Now Available
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      OA16.02 - Shared Decision Making (SDM) and Patient Decision Aids (PDAs) in Lung Cancer: Survey of Patients, Significant Others or Caregivers (Abstract under Embargo until December 4, 7:00 CET) (Now Available) (ID 4767)

      D..R. Camidge

      • Abstract
      • Presentation
      • Slides

      Background:
      Shared decision making (SDM) between the patient and their physicians is recognized as a desirable goal. When one treatment option is not clearly superior to another, PDAs can help present risks and benefits in a simple, visual format. Of the 600 plus validated PDAs, less than 60 of these are designed for cancer treatment decisions, and only 10 deal with lung cancer diagnosis or treatment (www.ohri.ca/decisionaid). A survey of lung cancer patients or their significant others/caregivers collected information regarding decision making experiences, and the perceived usefulness of PDAs.

      Methods:
      A survey (via SurveyMonkey) was sent to lung cancer patients/caregivers/significant others who had signed up for email communication from the Bonnie Addario Lung Cancer Foundation (ALCF), Global Resource for Advancing Cancer Education (GRACE), or the University of Colorado. The survey collected information regarding demographics, categorization of the difficult problem, and the sources of problems encountered during decision making. A PDA regarding prophylactic cranial irradiation (PCI) for limited small cell cancer was made available, and opinions were sought regarding the usefulness of this format.

      Results:
      190 responses were obtained (123 patients, 67 other). This was predominantly a well-educated, white, North American population, with advanced disease, with more women than men (75% vs 25%). 115 (61%) of respondents had faced a difficult decision, women more so than men. Decisions regarding systemic therapy were the most commonly perceived difficult decision (58%) and/or tests that were done/not done (34%). Sources of difficulty were identified as insufficient information (44%), or conflicting information or recommendations from their physicians (34%). The amount of information available was categorized as insufficient, just right, too much or difficult to know in 14%, 22%, 2%, 50%. Men were more likely to indicate that they had sufficient information, 39% vs 14%, p< 0.05. Most patients desired SDM, with only 9% expressing the desire to make the decision alone. However, 26% perceived that they had done so. Fortunately, only 8% of respondents expressed regret regarding their decision. Of 90 respondents who viewed the PCI PDA, 61% felt that this type of decision aid would have been helpful. There were no gender differences regarding opinions towards the PDA, the desire for SDM, or the perception that it had occurred.

      Conclusion:
      Lung cancer patients desire shared decision making. Improvements in this process are perceived as needed, possibly with PDAs.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      P2.03b-016 - Tesevatinib in NSCLC Patients with EGFR Activating Mutations and Brain Metastases (BM) or Leptomeningeal Metastases (LM) (Now Available) (ID 4649)

      D..R. Camidge

      • Abstract
      • Slides

      Background:
      Tesevatinib is a potent reversible EGFR inhibitor with strong preclinical evidence of brain penetration: brain:plasma ratios of 1-4 and brain:meninges ratios of 10-15 in rodents (AACR 2015 Abstract 2590). Tesevatinib was previously shown to have significant clinical activity in patients presenting with EGFR mutant NSCLC, but not in patients with T790M mutation. Approximately 25% of patients with EGFR activating mutations progress in the CNS, and metastases there have a low rate (10%) of T790M mutations.

      Methods:
      Patients with NSCLC driven by activating EGFR mutations who had BM or LM occurring or progressing while receiving erlotinib, gefitinib, or afatinib were treated with 300 mg of tesevatinib daily. Patients with BM had RECIST 1.1 measurable disease in the brain, and RECIST 1.1 evaluated response. Patients with symptomatic LM were diagnosed by either CSF cytology or MRI findings. Response was measured by improvement in symptoms, CSF cytology, and MRI. Patients with both BM and symptomatic LM were enrolled in the LM cohort. Target accrual is 20 patients in each cohort.

      Results:
      To date, 7 patients have been enrolled [2M:5F; median age 61 (36-66); 1 Asian], all with CNS symptoms. Four were in the BM cohort and 3 in the LM cohort. All had prior CNS radiotherapy, either WBRT or SRS or both. All had prior systemic therapy (median 3; range 1-6). Three patients had EGFR del 19, 3 had L858R, and 1 had L861Q. Gr ≥ 3 adverse events, regardless of relationship to study drug, have included Gr 3 prolonged QTc, Grade 3 hypokalemia, Gr 3 dehydration, Gr 3 UTI, and Gr 3 ALT elevation. Three patients had dose reductions due to asymptomatic QTc interval prolongation. Six out of the 7 patients had CNS symptom improvement, often occurring within 14 days of tesevatinib initiation. Two patients decreased steroids. One BM patient had marked improvement in right leg strength and a 19% reduction in the target BM on Study Day 23. One patient with BM and LM had resolution of LM symptoms, a 57% reduction in BM target lesion, and clearance of LM enhancement on MRI at Study Day 41.

      Conclusion:
      Early data from the first 7 patents in this ongoing clinical trial indicate that tesevatinib has clinical activity in the CNS in EGFR mutant disease manifesting as BM or LM in patients previously treated with erlotinib, gefitinib, or afatinib. An additional cohort of 20 treatment-naïve patients who have initial presentation with brain metastases is being added.

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    P3.02a - Poster Session with Presenters Present (ID 470)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      P3.02a-013 - Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Central Assessment and Updates from ALTA, a Pivotal Randomized Phase 2 Trial (Now Available) (ID 4046)

      D..R. Camidge

      • Abstract
      • Slides

      Background:
      Brigatinib, an investigational next-generation ALK inhibitor, has yielded promising activity in crizotinib-treated ALK+ NSCLC patients in a phase 1/2 trial (NCT01449461). As responses and adverse events (AEs) varied with starting dose, two brigatinib regimens are under evaluation in ALTA (NCT02094573).

      Methods:
      Patients with crizotinib-refractory advanced ALK+ NSCLC were randomized 1:1 to receive brigatinib at 90 mg qd (arm A) or 180 mg qd with a 7-day lead-in at 90 mg (arm B) and stratified by presence of brain metastases at baseline and best response to prior crizotinib. Primary endpoint was investigator-assessed confirmed ORR per RECIST v1.1.

      Results:
      222 patients were enrolled (arm A, n=112/arm B, n=110). Median age (A/B) was 51/57 years, 55%/58% were female, 74%/74% previously received chemotherapy, and 71%/67% had brain metastases. As of February 29, 2016, 64/112 (57%) patients in arm A and 76/110 (69%) patients in arm B were receiving brigatinib; median follow-up was 7.8/8.3 months. The Table shows investigator-assessed endpoints by arm and subgroup for select baseline characteristics. Independent review committee–assessed endpoints (A/B, n=112/n=110; as of May 16, 2016): confirmed ORR 48%/53%, median PFS 9.2/15.6 months. Any-grade treatment-emergent AEs (≥25% overall frequency; A/B, n=109/n=110 treated): nausea (33%/40%), diarrhea (19%/38%), headache (28%/27%), cough (18%/34%); grade ≥3 events (excluding neoplasm progression; ≥3% frequency): hypertension (6%/6%), increased blood CPK (3%/9%), pneumonia (3%/5%), increased lipase (4%/3%). A subset of pulmonary AEs with early onset (median onset: Day 2) occurred in 14/219 (6%) treated patients (3%, grade ≥3); 7/14 patients were successfully retreated. No such events occurred after escalation to 180 mg in arm B.

      Conclusion:
      In each arm, brigatinib yielded substantial responses and prolonged PFS, with an acceptable safety profile. 180 mg with 90 mg lead-in was not associated with increased early pulmonary events and showed a consistent improvement in efficacy, compared with 90 mg, particularly with respect to PFS.

      Investigator-Assessed Endpoints by Arm and Subgroup
      Confirmed ORR, n/N(%) Median PFS, months
      Arm A B A+B A B A+B
      All patients 50/112(45) 59/110(54) 109/222(49) 9.2 12.9 11.1
      Prior chemotherapy
      Yes 35/83(42) 44/81(54) 79/164(48) 8.8 12.9 11.8
      No 15/29(52) 15/29(52) 30/58(52) 9.2 8.1 9.2
      Race
      Asian 18/39(46) 18/30(60) 36/69(52) 8.8 11.1 11.1
      Non-Asian 32/73(44) 41/80(51) 73/153(48) 9.2 12.9 11.8
      Brain metastases at baseline
      Yes 31/80(39) 43/74(58) 74/154(48) 9.2 11.8 11.1
      No 19/32(59) 16/36(44) 35/68(51) 7.4 15.6 15.6
      Best response to prior crizotinib
      Partial+complete 36/71(51) 47/73(64) 83/144(58) 11.1 15.6 15.6
      Other 14/41(34) 12/37(32) 26/78(33) 7.4 12.9 9.2
      ORR=objective response rate PFS=progression-free survival


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    P3.02b - Poster Session with Presenters Present (ID 494)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02b-115 - Clinical Activity of Osimertinib in EGFR Mutation Positive Non Small Cell Lung Cancer (NSCLC) Patients (Pts) Previously Treated with Rociletinib (ID 4893)

      D..R. Camidge

      • Abstract

      Background:
      Both osimertinib and rociletinib were developed to target the EGFR resistance mutation T790M. Sequist, et al reported clinical activity with osimertinib in 9 pts previously treated with rociletinib[1]. We conducted a retrospective analysis at 8 institutions of pts treated with rociletinib, who discontinued the drug due to disease progression or intolerable toxicity and subsequently received osimertinib.

      Methods:
      We identified pts treated with rociletinib followed by osimertinib, as part of osimertinib's US expanded access program or via commercial supply. Clinical characteristics and outcomes were assessed. Frequency of clinical and radiologic assessments on osimertinib was at the discretion of the treating physician. For this retrospective review, reverse KM method was used to calculate the median follow-up; KM method was used for time-to-event endpoints.

      Results:
      45 pts were included in this analysis. Median age at the start of osimertinib was 66 years (43-86) and 71% were female. 28 pts had exon 19 deletions and 16 had L858R. Median duration of therapy on front line EGFR TKI was 18 months (5-54). Median starting dose of rociletinib was 625 mg bid (range 500-1000). The response rate (RR) and disease control rate (DCR; Response+Stable Disease) with rociletinib were 38% and 91%; median duration of rociletinib therapy was 6.2 months. 32 (71%) pts discontinued rociletinib for disease progression. 23 (51%) pts received other therapies (1-4) before starting osimertinib. 25 (56%) pts were known to have brain metastases at osimertinib initiation. RR and DCR with osimertinib were 33% and 82%. DCR in the brain was 88%. With a median follow-up of 7.1 months, median duration of osimertinib therapy in all patients was 8 months (95%CI- 6.6-NR; 64% censored). The 1-year overall survival (OS) rate on osimertinib was 70% (54%-91%). In the 32 pts who discontinued rociletinib due to progression, DCR with osimertinib was 75% and median duration of therapy was 7.8 months (4.6-NR). Neither duration of,or response to rociletinib treatment, nor interval between the two the drugs was associated with duration of osimertinib or OS after osimertinib using a Cox model adjusted for age and sex.

      Conclusion:
      Osimertinib can provide clinical benefit in EGFR mutation positive NSCLC patients previously treated with rociletinib. The clinical activity of osimertinib in these patients may be related to more potent inhibition of T790M mutation or ability to overcome resistance to rociletinib. Reference- 1. Sequist, et al. JAMA Oncology 2016