https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/202 2026-04-05T07:28:26Z 2026-04-05T07:28:26Z OHara, R. Liam, C. Kin Ahmad, A. Rozila Hsia, T. -C. Zhou, J. Kim, D. -W. Soo, R. Andrew Cheng, Y. Lu, S. Shin, S. Won Yang, J. Chih-Hsin Zhang, Y. Zhao, J. Bruns, R. Johne, A. Wu, Y. -L. https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63404 2023-12-13T11:01:41Z 20230923-01-01T00:00:00Z

Title: Tepotinib plus Gefitinib in Patients with EGFR-Mutant NSCLC with MET Amplification (METamp): Final Analysis of INSIGHT Authors: OHara, R.; Liam, C. Kin; Ahmad, A. Rozila; Hsia, T. -C.; Zhou, J.; Kim, D. -W.; Soo, R. Andrew; Cheng, Y.; Lu, S.; Shin, S. Won; Yang, J. Chih-Hsin; Zhang, Y.; Zhao, J.; Bruns, R.; Johne, A.; Wu, Y. -L. Abstract: Background In the INSIGHT trial primary analysis (NCT01982955; median follow-up: 21.8 months), tepotinib (a highly selective, once daily [QD] MET inhibitor) + gefitinib improved efficacy versus chemotherapy in patients with EGFR-mutant NSCLC, and resistance to anti-EGFR therapy due to METamp. Here, we report final analyses from INSIGHT (data cut-off: September 3, 2021; median follow-up: 57.5 months). Previously presented at AACR 2022. Methods Patients with EGFR-mutant (T790M-negative) NSCLC and anti-EGFR resistance, with METamp (MET gene copy number ≥5 and/or MET:CEP7 ≥2 by FISH) and/or MET overexpression (IHC 2+/3+), were randomized to tepotinib 500 mg (450 mg active moiety) + gefitinib 250 mg QD or chemotherapy. Primary endpoint was progression-free survival (PFS) per investigator. Preplanned analyses evaluated patients with METamp. Results 19/55 randomized patients (34.5%) had METamp (MET IHC 3+, n=17; median age: 60.4 years; never-smokers: 68.4%; prior EGFR inhibitors: gefitinib [57.9%], afatinib [21.1%], erlotinib [10.5%], and icotinib [10.5%]). Median duration of tepotinib + gefitinib was 11.3 months (range: 1.1–56.5), with treatment duration >1 year in six patients (31.6%), and >4 years in three patients (15.8%). Two patients continued treatment outside the study (total duration >5 years). Tepotinib + gefitinib improved PFS (hazard ratio [HR] 0.13; 90% confidence interval [CI]: 0.04, 0.43), overall survival (OS; HR 0.10; 90% CI: 0.02, 0.36), objective response rate, and duration of response versus chemotherapy (Table). Treatment-related Grade ≥3 adverse events occurred in seven patients (58.3%) with tepotinib + gefitinib, and five (71.4%) with chemotherapy; most reported (>20%) were increased amylase and increased lipase (both 33.3%) with tepotinib + gefitinib, and anemia, decreased white blood cell count, and decreased neutrophil count (all 28.6%) with chemotherapy. Conclusions Tepotinib + gefitinib greatly improved PFS and OS versus chemotherapy in patients with EGFR-mutant NSCLC with METamp.

20230923-01-01T00:00:00Z Wainberg, Z. Kang, Y. Lee, K. Qin, S. Yamaguchi, K. Kim, I. Saeed, A. Oh, S. Li, J. Turk, H. Teixeira, A. Hitre, E. Udrea, A. Cardellino, G. Guardeno Sanchez, R. Zahlten-Kumeli, A. Taylor, K. Enzinger, P. https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64079 2023-12-13T11:31:05Z 202306-01-01T00:00:00Z

Title: Bemarituzumab for treatment of previously untreated advanced and/or metastatic gastric and gastroesophageal cancer (GC): Final analysis of a randomized phase 2 trial (FIGHT) Authors: Wainberg, Z.; Kang, Y.; Lee, K.; Qin, S.; Yamaguchi, K.; Kim, I.; Saeed, A.; Oh, S.; Li, J.; Turk, H.; Teixeira, A.; Hitre, E.; Udrea, A.; Cardellino, G.; Guardeno Sanchez, R.; Zahlten-Kumeli, A.; Taylor, K.; Enzinger, P. Abstract: Background Bemarituzumab is a first-in-class, humanized IgG1 monoclonal antibody, selective for fibroblast growth factor receptor 2b (FGFR2b). In FIGHT, bemarituzumab + mFOLFOX6 demonstrated clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) compared with placebo + mFOLFOX6 among patients with FGFR2b-overexpressing GC (primary analysis data cutoff: September 23, 2020); here, we report the FIGHT final analysis (24 months after the last patient was enrolled). Methods Patients with GC, assessed for FGFR2b overexpression by immunohistochemistry (IHC) analysis (any 2+/3+ staining) and/or FGFR2 gene amplification by circulating tumor DNA, were randomized 1:1 to receive bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. Eligible patients were not known to be HER2 positive. The primary endpoint of PFS was centrally assessed. Results In the bemarituzumab (N=77) and placebo (N=78) groups, 59.7% and 66.7% of patients, respectively, had FGFR2b overexpression in ≥10% of tumor cells by IHC staining. One patient in each group was not treated. The data cutoff was May 13, 2022. Median PFS was 9.5 months (95% confidence interval [CI], 7.3-13.7) in the bemarituzumab group and 7.4 months (95% CI, 5.7-8.4) in the placebo group (hazard ratio [HR], 0.72 [95% CI, 0.49-1.08]). Median OS was 19.2 months (95% CI, 13.6-24.2) in the bemarituzumab group and 13.5 months (95% CI, 9.3-15.9) in the placebo group (HR, 0.77 [95% CI, 0.52-1.14]). Objective response rate (ORR) was 48.1% and 33.3% in the bemarituzumab and placebo groups, respectively; the difference in ORR was 14.4% (95% CI, -1.5 to 30.3). Treatment benefit was more pronounced in patients with FGFR2b overexpression in ≥10% of tumor cells by IHC staining: PFS: HR, 0.43 (95% CI, 0.26-0.73); OS: HR, 0.52 (95% CI, 0.31-0.85); and difference in ORR: 20.0% (95% CI, 0.6%-39.4%). No new safety concerns were identified. In the bemarituzumab and placebo groups, 100% and 98.7% of patients, respectively, had at least one treatment-emergent adverse event (TEAE); 82.9% and 75.3% of patients, respectively, reported grade ≥3 TEAEs. Study drug discontinuation due to TEAEs was higher in the bemarituzumab group (40.8%) than in the placebo group (5.2%). Study drug was discontinued for any-grade corneal events not resolved within 28 days; therefore, 77.4% (24/31) of patients discontinued bemarituzumab. In the bemarituzumab and placebo groups, corneal TEAEs were reported in 67.1% and 10.4% of patients, respectively, and were resolved/downgraded to grade 1 in 46.1% and 9.1% of patients, respectively. Median time to onset and resolution of ocular events was 16.9 weeks and 24.4 weeks, respectively, for the bemarituzumab group and 11.6 weeks and 1.4 weeks, respectively, for the placebo group. Conclusions After 24 months of follow-up, patients with FGFR2b overexpression treated with bemarituzumab + mFOLFOX6 continued to show clinically meaningful outcomes over patients treated with placebo + mFOLFOX6; more pronounced efficacy was observed in patients with ≥10% of tumor cells with 2+/3+ FGFR2b IHC staining intensity. Randomized phase 3 trials focused on patients with ≥10% of tumor cells to confirm the observed clinical benefit of bemarituzumab are ongoing.

202306-01-01T00:00:00Z Kim, Dong Hyun Lim, Yoojoo Ock, Chan-Young Park, Gahee Park, Seonwook Song, Heon Ma, Minuk Mostafavi, Mohammad Kang, Eun Joo Ahn, Myung-Ju Lee, Keun-Wook Kwon, Jung Hye Yang, Yaewon Choi, Yoon Hee Kim, Min Kyoung Ji, Jun Ho Yun, Tak Kim, Sung-Bae Keam, Bhumsuk https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64311 2024-07-11T10:30:26Z 2023-12-01T00:00:00Z

Title: Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a predictive biomarker for axitinib in adenoid cystic carcinoma Authors: Kim, Dong Hyun; Lim, Yoojoo; Ock, Chan-Young; Park, Gahee; Park, Seonwook; Song, Heon; Ma, Minuk; Mostafavi, Mohammad; Kang, Eun Joo; Ahn, Myung-Ju; Lee, Keun-Wook; Kwon, Jung Hye; Yang, Yaewon; Choi, Yoon Hee; Kim, Min Kyoung; Ji, Jun Ho; Yun, Tak; Kim, Sung-Bae; Keam, Bhumsuk Abstract: Background: This study analyzed the predictive value of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib.Methods: Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole-side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI-powered spatial TIL analyzer.Results: Twenty-seven patients were included in the analysis. The best response was stable disease, and the median progression-free survival (PFS) was 11.1 months (95% CI, 9.2-13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm(2) (IQR, 8.3-73.0) and 180.4/mm(2) (IQR, 69.6-342.8), respectively. Patients with stromal TIL density >342.5/mm(2) exhibited longer PFS (p = 0.012).Conclusions: Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment.

2023-12-01T00:00:00Z Kim, Se Hyun Im, Seock-Ah Suh, Koung Jin Lee, Kyung-Hun Kim, Min Hwan Sohn, Joohyuk Park, Yeon Hee Kim, Ji-Yeon Jeong, Jae Ho Lee, Kyoung Eun Choi, In Sil Park, Kyong Hwa Kim, Hee-Jun Cho, Eun Kyung Park, So Yeon Kim, Milim Kim, Jee Hyun https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64412 2024-07-11T10:30:16Z 2023-12-01T00:00:00Z

Title: Clinical activity of nivolumab in combination with eribulin in HER2-negative metastatic breast cancer: A phase IB/II study (KCSG BR18-16) Authors: Kim, Se Hyun; Im, Seock-Ah; Suh, Koung Jin; Lee, Kyung-Hun; Kim, Min Hwan; Sohn, Joohyuk; Park, Yeon Hee; Kim, Ji-Yeon; Jeong, Jae Ho; Lee, Kyoung Eun; Choi, In Sil; Park, Kyong Hwa; Kim, Hee-Jun; Cho, Eun Kyung; Park, So Yeon; Kim, Milim; Kim, Jee Hyun Abstract: Aim: We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations.Methods: In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m2) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated.Results: Forty-five patients with HR+HER2-BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2-and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2-and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression >= 1%) and PD -L1-tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs.

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