Author of

• 30446

  +

  P1.01 - Advanced NSCLC (ID 158)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall

  • 30460

    +

    P1.01-12 - Trends in the National Cancer Institute (NCI) Sponsored Lung Cancer Clinical Trials Pre and Post NCI’s National Clinical Trials Network (NCTN) (ID 2645)

    09:45 - 18:00  |  Author(s): Edward Korn
    • Abstract

    Background
    

    On March 1, 2014, NCI launched the new NCTN, transforming NCI’s longstanding Cooperative Group Program. The NCTN coordinates and supports cancer clinical trials at more than 3,000 sites across the United States and Canada providing the infrastructure for NCI-funded trials to improve the lives of people with cancer.

    Method
    

    We reviewed 10 years of lung cancer treatment trials accrual data that included 5 years pre-NCTN trial activations and accruals to these trials between3/1/2009-2/28/2014 and 3/1/2014-2/28/2019 for post-NCTN.More than 3,800 patients were enrolled to lung cancer treatment clinical trials that activated pre-NCTN during the pre-NCTN period, while more than 2,300 were enrolled in the post-NCTN period. Histology identifiers of small cell vs. non-small cell and Phase II vs. Phase II/III or III were sorted.

    Result
    

    Table 1 Histology and Phase

    Trial Information		PRE-NCTN	POST-NCTN
    Number of trials		19	23
    Lead disease	Non-small cell lung cancer	15	22
    	Small cell lung cancer	4	1
    Phase	Phase II	13	11
    	Phase III (including II/III)	6	12

    Table 2 Trial Status

    		PRE-NCTN	POST-NCTN
    Trial status	Active	1	9
    	Closed	18	14
    Closed trials	Completed	8	6
    	Premature closure	10	8
    Among Prematurely Closed Trials
    Reasons for premature closure	Interim monitoring	4*	5
    	Drug supply/external information		1
    	Unacceptable toxicity	2
    	Inadequate accrual rate	4	2

    While there is a 20% increase in activated trials in post NCTN era, the number of phase III trials has doubled. A decrease in small cell lung cancer clinical trials due to lack of active new drugs is noted. Enrollment of non-whites and females improved in post NCTN era and there was an increase in ethnicity and gender data capture. Additional demographic data will be available to report at the meeting and a discussion of evolving treatment trends.

    Conclusion
    

    In this era of precision medicine trials, the total treatment trial patient numbers have deceased, however; the screening part of the NCI master protocol trials were excluded from this analysis. ALCHEMIST enrolled patients 3264 patients that were screened but not enrolled in the treatment arms of ALCHEMIST. All the patients screened on ALCHEMIST will be followed for a total of 10-years and their tumor will also undergo genomic analysis. Similarly, LungMap screening trial included 1278 patients that did not get assigned to any treatment protocol.

• 30601

  +

  P2.01 - Advanced NSCLC (ID 159)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30605

    +

    P2.01-04 - NCI-NRG Oncology ALK PROTOCOL (NRG-LU003): A Biomarker-Driven Protocol for Previously Treated ALK-Positive Non-Squamous NSCLC Patients      (ID 2021)

    10:15 - 18:15  |  Author(s): Edward Korn
    • Abstract

    Background
    

    Currently, the 1^stgeneration ALK inhibitor crizotinib and 2^ndgeneration ALK inhibitors ceritinib, alectinib and brigatinib are FDA-approved for the treatment of advanced ALK-positive NSCLC. The 3^rdgeneration ALK inhibitor lorlatinibrecentlyreceived accelerated approval for patients after failure of a 2^ndgeneration inhibitor.

    2^ndgeneration ALK inhibitors are widely used in crizotinib-resistant patients and have recently replaced crizotinib as first-line therapy for newly diagnosed patients. There is an urgent need to define the optimal therapy for patients who have become resistant to a second-generation ALK inhibitor. Pre-clinical data and small case series suggest that the presence/absence of ALK resistance mutations or the specigic ALK mutation may serve as a critical biomarker to guide selection of therapy, particularly in the setting of relapse on a 2^ndgeneration ALK inhibitor when ALK resistance mutations are more common,

    Method
    

    NRG-LU003 proposes to study ALK-positive non-squamous NSCLC patients who develop resistance to a second-generation ALK inhibitor, in order to establish a treatment algorithm for these patients based on resistance mechanisms.Patients will undergo tissue biopsy along with blood sampling for cfDNA analysis. One of the aims of the study is to establish the concordance between tissue and liquid biopsies; liquid biopsy may replace tissue biopsy after the first 200 patients enrolled, depending on the concordance and in consultation with CDRH/FDA. Treatments will be selected based on preclinical and clinical data demonstrating activity of treatment particular inhibitor against the specific ALK mutation or resistance mechanism identified. If no ALK resistance mutations are identified, patients will be randomized to receive either a next-generation ALK inhibitor they have not previously received or pemetrexed-based therapy with cisplatin or carboplatin.

    Target accrual is 660 patients and primary objective is to assess whether ALK kinase domain mutations (e.g., G1202/C1156/I1171/L1196/V1180/F1174 mutations) associated with drug resistance are predictive of objective response to subsequent ALK inhibitor therapy, to assess whether subsequent pemetrexed based chemotherapy improves objective response compared to ALK inhibitor therapy for patients with no ALK resistance mutations, and to evaluate objective responses of patients with specific genetic alterations (e.g., ALK L1198F, compound mutations, or high-level MET amplification) treated with crizotinib.

    Mutation	STUDY DRUG	STUDY DRUG	STUDY DRUG	STUDY DRUG	STUDY DRUG	STUDY DRUG	STUDY DRUG
    G1202, G1202del, G1202R	lorlatinib			brigatinib
    C1156Y	lorlatinib		alectinib	brigatinib
    I1171	lorlatinib	ceritinib		brigatinib
    L1196, L1196M	lorlatinib	ceritinib	alectinib	brigatinib	ensartinib
    V1180	lorlatinib	ceritinib		brigatinib
    F1174	lorlatinib		alectinib	brigatinib
    Compound mutation	lorlatinib
    ALK L1198F (alone/ in combination with another ALK mutation)						crizotinib
    MET amplification						crizotinib
    No ALK-resistance mutations*	lorlatinib	ceritinib	alectinib	brigatinib	ensartinib		Pemetrexed + Cisplatin or Carboplatin

    Result
    

    "Section not applicable"

    Conclusion
    

    This study has been approved and is open for enrollment through the National Clinical Trials Network (NCTN).

    This project is supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI)