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Min Hee Hong
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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): Min Hee Hong
- Abstract
- Presentation
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.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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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: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 106
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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): Min Hee Hong
- Abstract
- Presentation
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.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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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): Min Hee Hong
- Abstract
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.
6f8b794f3246b0c1e1780bb4d4d5dc53
