Author of

• 25702

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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: 1
  • Moderators:
  • Coordinates: 9/24/2018, 10:30 - 12:00, Room 105

  • 27883

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    OA02.05 - CK-101 (RX518), a Third Generation Mutant-Selective Inhibitor of EGFR in NSCLC: Results of an Ongoing Phase I/II Trial (ID 11982)

    11:15 - 11:25  |  Author(s): Naiyarat Prasongsook
    • Abstract
    • Presentation
    • Slides

    Background
    

    CK-101 (also known as RX518) is a novel, oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and resistance mutations, with minimal activity on wild-type EGFR. CK-101 is being studied in an ongoing first-in-human, multicenter, Phase I/II trial in advanced non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations and other advanced malignancies in the US, Australia, New Zealand and Thailand (NCT02926768). Following dose escalation in which 18 pts received CK-101 in dose groups ranging from 100 mg to 1200 mg/day, a first dose-expansion cohort was enrolled at 400 mg bid.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Eligible pts in dose escalation had a confirmed diagnosis of NSCLC or any advanced solid tumor where targeting EGFR was reasonable. Eligible pts in dose-expansion had a confirmed diagnosis of either (1) EGFR mutation-positive advanced or metastatic NSCLC without prior exposure to EGFR-TKI therapy, or (2) T790M-positive advanced or metastatic NSCLC with disease progression on previous EGFR-TKI therapy, with no limit on number of prior lines of systemic therapy.

    4c3880bb027f159e801041b1021e88e8 Result
    

    As of 25 June 2018, 37 pts were treated in dose escalation and expansion and evaluable for safety; median age 59 years, 51% male, 51% Asian, 84% ECOG PS 1. No DLTs or treatment-related SAEs were reported. Most common treatment-emergent adverse events: nausea (16%), diarrhea (14%), lacrimation increased (14%) and vomiting (11%), all grade 1/2 except one grade 3 diarrhea; no grade 4. In dose-expansion, 19 pts were treated with CK-101 at a dose of 400 mg bid and evaluable for response; 8/19 (42%) pts were treatment-naïve, 6/19 (32%) pts had brain metastases; 16/19 (84%) pts remained on treatment. Disease control rate was 100% (19/19), with 16/19 pts (84%) experiencing target lesion reduction versus baseline and 8 pts achieving a partial response (7 confirmed, 1 pending confirmation). In treatment-naïve pts, 6/8 (75%) pts achieved a partial response. In pts with brain metastases, 3/6 (50%) pts achieved a partial response. Higher drug exposures were associated with higher response rate with a confirmed ORR of 55% (6/11) in pts achieving Cmax >400 ng/mL. Median duration of response and progression-free survival were not reached as of the data cutoff.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    CK-101 was well tolerated with a manageable safety profile. Durable anti-tumor activity was observed, particularly in treatment-naïve pts. Further study is ongoing to establish the optimal dose to maximize therapeutic effect in a planned Phase 3 study in treatment-naïve EGFR-mutant NSCLC pts.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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• 25963

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  P3.09 - Pathology (Not CME Accredited Session) (ID 975)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27584

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    P3.09-08 - Tumor Heterogeneity and Molecular Profile of NSCLC in Thai Population (ID 14016)

    12:00 - 13:30  |  Author(s): Naiyarat Prasongsook
    • Abstract
    • Slides

    Background
    

    Oncogenic driven mutation is the key to develop targeted therapy in lung cancer. Different ethnicity and tumor heterogeneity affect the prevalence of molecular alteration. This study aimed to explore the unique molecular profile of lung adenocarcinoma in Thai population.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We studied 166 lung adenocarcinoma patients’ molecular profile using Next Generation Sequencing (NGS) on 45 genes lung cancer panel (Ion Torrent system). Variants from NGS with coverage of higher than 1000X and cut off at 2% alternate variant frequency were considered positive. We validated the positive mutation of EGFR, BRAF, and KRAS by Real- Time PCR using the Amoy DX kit.

    4c3880bb027f159e801041b1021e88e8 Result
    

    This study found 68%(113/166) of EGFR mutation, 9.6%(16/166) of BRAF V600E, 32.5% (54/166) of KRAS mutation, 9%(15/166) of MET exon14 splice site, 4.8% (8/166) AKT mutation (E17K), 2.4% (4/166) of ROS1 mutation, 0.6% (1/166) of PIK3CA mutation (H1047R), and 0.6% (1/166) of PTEN mutation. Furthermore, we also found 40 patients (24.1%) who had more than one mutation in each person. We further validated the positive results by Real-Time PCR. Thirteen patients were obtained tissue from different organs and some with different period of time. T790M usually develop later in EGFR-positive patients who failed 1^st or 2^nd generation EGFR-TKI. Two patients (patient 5&9) who had lung surgery different lobe in same operation, had different mutation in tissues and one patient (patient 13) who obtained tissue from lung and pleural effusion cell block in different period of time had totally different mutation (Table1).

    Table1 Tumor heterogeneity profile in lung cancer patients

    case	Hetrogenety in different organ	date obtained tissue	Gene mutation
    			EGFR	KRAS	ROS	PTEN	AKT	MET	BRAF
    1	RLL lobectomy	12-Jun-2012	Exon 19 Deletion	negative	negative	negative	negative	negative	negative
    	Right lung	4-May-2016	Exon 19 Deletion T790M	negative	negative	negative	negative	negative	negative
    2	lymph node	16-Mar-2017	negative	negative	negative	negative	negative	negative	negative
    	Bone	9-Apr-2017	negative	negative	negative	negative	negative	negative	negative
    3	Right upper lung biopsy	20-Jan-2016	Exon 19 Deletion	negative	negative	negative	negative	negative	negative
    	Lung biopsy	31-Mar-2017	T790M	negative	negative	negative	E17K	negative	negative
    4	lymph node	13-Jan-2016	negative	G12A	negative	negative	negative	negative	negative
    	skin	17-Jan-2016	negative	G12V G12D	negative	negative	negative	negative	negative
    	left humerous	30-Jun-2016	negative	G12V	negative	negative	negative	negative	negative
    5	RML lobectomy	13-Nov-2013	Exon 19 Deletion	G13D	negative	negative	negative	negative	negative
    	LUL lobectomy	14-May-2014	negative	G12D G13D	negative	R233*	negative	negative	negative
    	LUL lobectomy	14-May-2014	negative	G12V G12D	D2033N	negative	negative	negative	negative
    6	Right pleura biopsy	11-Jan-2016	Exon 19 Deletion	negative	negative	negative	negative	negative	negative
    	RUL biopsy	1-Mar-2017	Exon 19 Deletion	negative	negative	negative	negative	negative	negative
    7	RUL biopsy	28-Sep-2015	L858R	negative	negative	negative	negative	negative	negative
    	Left pleural fluid cell block	27-Jun-2016	negative	negative	negative	negative	negative	negative	negative
    8	Right pleural fluid cell block	25-Mar-2016	Exon 19 Deletion	negative	negative	negative	negative	negative	negative
    	Left pleural fluid cell block	9-Dec-2016	T790M	negative	negative	negative	negative	negative	negative
    9	RML lobectomy	14-Mar-2013	negative	G13S	negative	negative	E17K	negative	negative
    	RLL wedge resectionRLL lo	30-Mar-2017	G719A L861Q	negative	negative	negative	negative	negative	negative
    10	RLL lobectomy	26-Aug-2013	negative	G12C G12D	negative	negative	negative	negative	negative
    	Left lingular lobe segmental resection	9-Oct-2014	negative	G12D	negative	negative	negative	negative	negative
    	LUL wedge resection	11-Feb-2016	negative	G12D	negative	negative	negative	negative	negative
    	LUL lobectomy	4-Jun-2017	negative	G12D	negative	negative	negative	negative	negative
    	LLL resection	9-Oct-2014	negative	G12D	negative	negative	negative	negative	negative
    11	Right pleural cell block	21-Jul-2014	L858R	negative	negative	negative	negative	c.3028G>A exon 14 splicing	negative
    	Ascites	9-Jun-2017	T790M L858R	negative	negative	negative	negative	negative	negative
    12	LUL biopsy	24-Feb-2015	L858R	negative	negative	negative	negative	negative	V600E
    	Lt lung biopsy	8-Jul-2016	L858R	negative	negative	negative	negative	negative	negative
    13	RLL biopsy	14-Oct-2015	negative	negative	negative	negative	negative	c.3028+1G>T exon 14 splicing	negative
    	pleural fluid cell block	15-Nov-2016	Exon 19 Deletion T790M	negative	negative	negative	negative	negative	negative

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Thai populations have unique molecular alteration compared to the other ethnicities, especially, higher of BRAF V600E and MET exon14 splice site. Our population also has high co-mutation prevalence. Tumor heterogeneity is needed to explore in the larger cohort.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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