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Joo-Hang Kim
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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: 2
- 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): Joo-Hang Kim
- 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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MA26.10 - CNS Activity of Ramucirumab in Combination with Osimertinib in Patients with Advanced T790M-Positive EGFR-Mutant NSCLC (ID 12295)
14:35 - 14:40 | Author(s): Joo-Hang Kim
- Abstract
- Presentation
Background
Many patients with NSCLC develop central nervous system (CNS) metastasis. Osimertinib, a novel third-generation EGFR tyrosine kinase inhibitor (TKI), has previously demonstrated CNS and systemic efficacy in patients with EGFR-mutant NSCLC. Combination of an EGFR TKI with a VEGF/VEGFR2-directed monoclonal antibodies (mAb) have shown promising results in EGFR-mutant NSCLC. Ramucirumab, human IgG1 VEGFR2 mAb, was used in combination with osimertinib. Planned exploratory and CNS response analyses aim to examine the safety/efficacy of ramucirumab+osimertinib in patients with CNS metastasis.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this ongoing, open-label, multicenter Phase 1 study (NCT02789345), patients with T790M-positive EGFR-mutant (Ex19del or L858R) NSCLC who had relapsed after first-line EGFR TKI therapy were enrolled. Patients with asymptomatic and stable CNS metastasis (with/without prior radiotherapy) were eligible. Primary objective of the study was to assess safety and tolerability of ramucirumab+osimertinib. Secondary endpoints include objective response rate (ORR) and disease control rate (DCR). Exploratory endpoints relevant to CNS include CNS ORR and CNS DCR.
4c3880bb027f159e801041b1021e88e8 Result
Patients (N=25) were 45-80 years (median 64) with ECOG-PS 0 (n=3) or 1 (n=22) and 10 patients had CNS metastasis at enrollment while 15 never had CNS metastasis. Patients with CNS metastasis could have had prior radiotherapy (n=7) or no radiotherapy (n=3) to the CNS. Median follow-up time was 7.23 months. Fifteen patients remained on study treatment (five with CNS metastasis, ten without). TEAEs of interest (CNS metastasis, no CNS metastasis), such as headache (4/10, 5/15), vomiting (3/10, 4/15), and nausea (2/10, 4/15), were observed with comparable rates in patients with or without CNS metastasis. One patient developed TEAE of cerebral hemorrhage (Grade 1), related to CNS metastasis, but unrelated to study treatment, according to the investigator. Another patient with CNS metastasis developed Grade 5 TRAE of subdural hemorrhage, unrelated to CNS metastasis, ~7 weeks after the last dose of ramucirumab. Only one patient with CNS metastasis had measurable CNS lesions (tumor shrinkage of 24% [SD] as best response). The other nine patients with CNS metastasis had non-measurable CNS lesions, one of whom had a CNS complete response; his systemic best response was SD. The rest of patients had CNS non-CR/non-PD. To date, one patient (1/25) developed CNS progression (due to new CNS lesion); her CNS best response was SD.
8eea62084ca7e541d918e823422bd82e Conclusion
Ramucirumab+osimertinib showed potential antitumor activity in the CNS. Patients with CNS metastasis, with/without prior radiotherapy, appeared to tolerate this combination similarly to patients without CNS metastasis.
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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P1.01-21 - Safety of Durvalumab Retreatment in Advanced NSCLC Patients Who Progressed Following Initial Disease Control In ATLANTIC (ID 12386)
16:45 - 18:00 | Author(s): Joo-Hang Kim
- Abstract
Background
In ATLANTIC, patients who completed a year of durvalumab (anti-PD-L1) treatment but later progressed off therapy were eligible for retreatment. We evaluated safety in these patients compared with the overall study population.
a9ded1e5ce5d75814730bb4caaf49419 Method
ATLANTIC (NCT02087423) was a Phase 2, open-label, single-arm trial in patients with Stage IIIB–IV NSCLC who had received ≥2 prior systemic treatment regimens, including one platinum-based. The study included three independent cohorts. In C1 (EGFR+/ALK+) and C2 (EGFR−/ALK−), enrollment was enriched for patients with ≥25% of tumor cells (TC) expressing PD-L1, while patients in C3 (EGFR−/ALK−) only had PD-L1 TC ≥90%. Patients received durvalumab 10 mg/kg q2w for ≤12 months. Patients who achieved and maintained disease control but then progressed after completing the initial 12-month treatment period were offered retreatment for a maximum of 12 months of further treatment. Safety and tolerability was a secondary outcome.
4c3880bb027f159e801041b1021e88e8 Result
As of November 7, 2017, of 442 patients in the ATLANTIC full analysis set, 102 (23.1%) had completed 12 months of initial treatment and 95 (21.5%) had disease control at the end of initial treatment. A total of 40 patients started retreatment. The median actual duration of exposure to durvalumab was 16.0 weeks (range 1–62; 40.1% of patients on treatment for ≥24 weeks) during initial treatment and 18.1 weeks (range 2–52; 37.5% of patients on retreatment for ≥24 weeks) during retreatment. The table shows safety during initial treatment and retreatment.
8eea62084ca7e541d918e823422bd82e ConclusionInitial treatment (n=444)
Retreatment phase (n=40)
Cohort,* n (%)
C1 (EGFR+/ALK+)
111 (25.0)
7 (17.5)
C2 (EGFR−/ALK−)
265 (59.7)
26 (65.0)
C3 (EGFR−/ALK−; TC ≥90%)
68 (15.3)
7 (17.5)
Any TRAE, n (%)
256 (57.7)
19 (47.5)
Grade ≥3 TRAEs
42 (9.5)
6 (15.0)
TRAEs leading to death
0
2 (5.0)†
Serious TRAEs
28 (6.3)
4 (10.0)
TRAEs leading to discontinuation
10 (2.3)
4 (10.0)
Safety analysis set. *A more detailed analysis of exposure and safety by cohort will be presented. †Causes of death were: pneumonitis and respiratory failure; cardiac arrest. TRAE=treatment-related adverse event.
A large proportion of patients (37.5%) maintained retreatment for ≥24 weeks, suggesting that patients who originally completed 12 months of treatment can tolerate sustained retreatment. The tolerability profile of durvalumab upon retreatment was similar to that seen during initial treatment, although there were two treatment-related deaths during the retreatment phase. Retreatment with anti-PD-L1 may be feasible for selected patients with NSCLC who demonstrate original benefit and progress off therapy.
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: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-74 - Docetaxel-Related Febrile Neutropenia (FN) And Patient Reported Symptoms/ QOL (PROs) in East Asian (EA) and Non-EA Patients (ID 11871)
16:45 - 18:00 | Author(s): Joo-Hang Kim
- Abstract
Background
A post hoc analysis of JVCG, a Japanese phase 2 trial suggested that the QOL (quality of life) deteriorated more rapidly in patients with docetaxel-related FN than in patients without FN. A post hoc analysis of REVEL, a global phase 3 trial, was performed to explore the association between FN and PROs in East Asian (EA) (Korea, Taiwan) and Non-EA patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
Lung Cancer Symptom Scale (LCSS) and EQ-5D-3L were assessed at baseline, every cycle, at discontinuation and 30-day follow up. The summary statistics of LCSS total score and EQ-5D Visual Analog Scale (VAS) score were calculated. Time to deterioration (TtD) was defined as the time from randomization to the first 15-mm increase from baseline for the LCSS and first 15% decrease for the EQ-5D VAS and analysed with the Kaplan-Meier method and Cox proportional hazard model by treatment-emergent FN status regardless of assigned treatment. Also the changes in LCSS total score and EQ-5D VAS score from baseline to the treatment completion were summarized.
4c3880bb027f159e801041b1021e88e8 Result
1253 patients randomized to receive RAM+DOC (EA: n=43 and Non-EA: 585) or PLA+DOC (n=46 and 579). FN occurred in 21.3% of EA and 12.3% of Non-EA patients. Patient compliance with the LCSS and EQ-5D were 84.2% and 84.4%, respectively in EA and 82.7% and 83.2% in Non-EA patients. For EA patients, HRs (95% CI) for TtD were 0.572 (0.250, 1.313) in LCSS total and 0.792 (0.350, 1.790) in EQ-5D VAS, indicating longer TtD in PROs for patients without FN. For Non-EA patients, HRs (95% CI) for TtD were 0.994 (0.728, 1.357) in LCSS total and 1.023 (0.787, 1.330) in EQ-5D VAS and there seemed to be no difference in TtD between patients with and without FN. At treatment completion, the unadjusted mean change from baseline of LCSS total was numerically lower in EA patients without FN: 12.97 (with FN) vs 5.94 (without FN) (p=0.1748) and significantly lower in Non-EA patients without FN: 10.50 (with FN) vs 5.55 (without FN) (p=0.0147), demonstrating a greater PROs deterioration in patients with FN.
8eea62084ca7e541d918e823422bd82e Conclusion
PROs of EA patients with FN deteriorated more rapidly than in those without FN in contrast with non-EA patients. This finding was consistent with a result in the Japanese phase 2 JVCG trial. Also Non-EA patients without FN maintained their PROs significantly better than patients with FN upon treatment completion. This trend was also shown in EA patients. Prevention of docetaxel-related FN may contribute to maintaining QOL.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.CR - Case Reports (Not CME Accredited Session) (ID 984)
- 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.CR-16 - A Case of Toxic Hepatic Event Occurring in Combination Treatment with Nivolumab and Anti-Tuberculosis in Advanced Lung Cancer (ID 14387)
12:00 - 13:30 | Author(s): Joo-Hang Kim
- Abstract
Background
Nivolumab, an immune checkpoint inhibitor, has been considered one of the standard treatments for previously treated advanced non-small-cell lung cancer. There is a not well known about the treatment and complications of tuberculosis in advanced lung cancer patients treating with nivolumab. We report a new case, toxic hepatic event occurring in combination treatment with nivolumab and anti-tuberculosis in advanced lung cancer patient.
a9ded1e5ce5d75814730bb4caaf49419 Method
The patient was 60-year-old man with advanced lung cancer. He had been treated for lung cancer stage IV by nivolumab for 15 months. Chest computed tomography showed a new developed wedge shaped consolidation in right upper lobe posterior segment. However, there was grossly no interval change of residual tumoral lesion in left upper lobe. Nivolumab treatment was discontinued to confirm metastasis. In bronchoscopic examination, we found endobronchial mass like lesion in right upper lobe anterior segment posterior portion, and bronchoscopic biopsy was done for pathologic diagnosis. The specimen showed chronic granulomatous inflammation with necrosis, suggestive of tuberculosis, but PAS and AFB stains was negative. However, Mycobacterium tuberculosis polymerase chain reaction (TB-PCR) revealed positive finding, so the new consolidative lesion was confirmed as pulmonary tuberculosis infection, not metastasis. The patient began receiving anti-tuberculosis treatment.
4c3880bb027f159e801041b1021e88e8 Result
After 1 month anti-tuberculosis treatment, he complained no adverse effect and the laboratory finding was normal range. Thus, he resumed nivolumab treatment. However, abnormalities in liver function tests (LFT) were observed after 2 weeks nivolumab treatment. Anti-tuberculosis medication and nivolumab was discontinued for control the elevated LFT. In further evaluation, he was likely to be drug-induced toxic hepatitis, and no other causative factor was found to affect hepatic function.
8eea62084ca7e541d918e823422bd82e Conclusion
This is the first report of toxic hepatic event occurring in combination treatment with nivolumab and anti-tuberculosis in lung cancer patient. Anti-PD L1 antibody immunotherapy is known to upregulate the immune response against micro-organisms, but the patient was infected with the pulmonary tuberculosis. Although the mechanism is unknown, nivolumab combination treatment seems to increase the risk of toxic hepatitis in tuberculsis treatment. Thus, we should pay attention to liver function changes in combination treatment with nivolumab and anti-tuberculosis.
6f8b794f3246b0c1e1780bb4d4d5dc53
