Biomedical subjects

Do-Youn Oh

Publications and source records attributed to Do-Youn Oh.

3 recordsLinked to original sources

PubMed2026

Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial.

IMPORTANCE: In the TOPAZ-1 trial's primary analysis, durvalumab plus gemcitabine and cisplatin (GemCis) showed statistically significant improved overall survival (OS) vs placebo plus GemCis with comparable safety between treatment groups in participants with advanced biliary tract cancer (aBTC). Durvalumab plus GemCis was recently established as the first-line standard of care among patients with aBTC. OBJECTIVE: To evaluate 4-year OS and safety of durvalumab plus GemCis in participants with aBTC. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the global, double-blind, placebo-controlled, phase 3 TOPAZ-1 randomized clinical trial included participants 18 years and older with histologically confirmed unresectable, locally advanced, or metastatic biliary tract adenocarcinoma. In the TOPAZ-1 trial, patients were enrolled from April 2019 to December 2020 at 105 sites in 17 countries. Data cutoff was February 28, 2025. INTERVENTION: Participants received intravenous durvalumab, 1500 mg, or placebo plus gemcitabine, 1000 mg/m2, and cisplatin, 25 mg/m2, on days 1 and 8 every 3 weeks for up to 8 cycles, followed by durvalumab or placebo monotherapy every 4 weeks. MAIN OUTCOMES AND MEASURES: OS, duration of treatment exposure, serious adverse events, and adverse events resulting in discontinuation were assessed approximately 48 months after the last participant was randomized. RESULTS: Overall, 685 participants were randomized, with 341 receiving durvalumab plus GemCis (median [range] age, 64 [20-84] years; 172 [50.4%] female) and 344 receiving placebo plus GemCis (median [range] age, 64 [31-85] years; 168 [48.8%] female). Median (range) follow-up in censored participants was 56.9 (1.7-67.2) months for participants who received durvalumab plus GemCis and 50.7 (0.9-62.6) months for participants who received placebo plus GemCis. Median OS was 13.0 (95% CI, 11.6-14.1) months for durvalumab plus GemCis and 11.4 (95% CI, 10.1-12.5) months for placebo plus GemCis (hazard ratio, 0.75; 95% CI, 0.64-0.88); 48-month OS rate was 11.8% vs 4.3%, respectively. The rate of serious adverse events possibly related to treatment was similar between arms (52 of 338 participants [15.4%] in the durvalumab plus GemCis arm vs 59 of 342 participants [17.3%] in the placebo plus GemCis arm). In the durvalumab plus GemCis and placebo plus GemCis arms, 21 of 338 participants (6.2%) and 18 of 342 participants (5.3%), respectively, experienced adverse events leading to study drug discontinuation. CONCLUSIONS AND RELEVANCE: In this post hoc analysis of the phase 3 TOPAZ-1 randomized clinical trial, durvalumab plus GemCis demonstrated long-term survival benefit and a clinically manageable safety profile, supporting its use as a first-line treatment for aBTC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03875235.

Humans↗

PubMed2026

Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data.

Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1-2 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per RECIST v1.1. Duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety were also assessed. Twenty-four patients (papillary TC, n = 21; follicular TC, n = 2; poorly DTC, n = 1) were included (data cut-off: 20 July 2024). ORR was 79% (95% confidence interval (CI): 58-93); best responses were complete response in 3 (13%) patients, partial response in 16 (67%), stable disease in 3 (13%), progressive disease in 1 (4%) and not evaluable in 1 (4%). Median DoR and PFS were 35 (95% CI: 22-not estimable (NE)) and 44 (95% CI: 35-NE) months, respectively; 6-year OS rate was 71% (95% CI: 50-91). Six patients remained on treatment. Treatment-related adverse events (TRAEs) were mainly grade 1/2; no patients permanently discontinued treatment due to TRAEs. Larotrectinib continues to demonstrate durable disease control, extended survival and a favourable long-term safety profile in patients with advanced TRK fusion DTC requiring systemic therapy.

Humans↗

PubMed2026

Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma.

PURPOSE: This phase Ib/II trial (NCT04276493) assessed the antitumor activity, safety, and pharmacokinetics (PK) of zanidatamab in combination with tislelizumab and chemotherapy in patients with advanced HER2-positive (HER2+) gastric cancer/gastroesophageal junction cancer (GEJC). PATIENTS AND METHODS: Adult patients with previously untreated, unresectable, locally advanced/metastatic HER2+ gastric cancer/GEJC received zanidatamab 30 mg/kg i.v. (cohort A) or zanidatamab 1800 mg i.v. (weight <70 kg)/2,400 mg i.v. (weight ≥70 kg; cohort B) once every 3 weeks (Q3W). Both cohorts received tislelizumab 200 mg i.v. once every 3 weeks and standard chemotherapy [capecitabine and oxaliplatin (CAPOX)] once every 3 weeks. Primary endpoints were investigator-assessed confirmed objective response rate (cORR) per RECIST v1.1, in addition to the frequency and severity of adverse events (AE) and serious AEs. Secondary endpoints included investigator-assessed progression-free survival (PFS), duration of response (DoR), overall survival (OS), PK, and immunogenicity of zanidatamab. RESULTS: As of December 7, 2023, 33 patients (cohort A, n = 19; cohort B, n = 14) received treatment. The confirmed objective response rate was 75.8%; the median duration of response, progression-free survival, and overall survival were 23.3, 16.7, and 32.4 months, respectively. The most common treatment-related AEs (TRAEs) were diarrhea (100%), nausea (63.6%), and decreased appetite (48.5%). Treatment-related AEs of grade ≥3 were reported in 22 (66.7%) patients; diarrhea was the most common (27.3%). CONCLUSIONS: Zanidatamab, in combination with tislelizumab and CAPOX, demonstrated clinically meaningful antitumor activity with a manageable safety profile as first-line therapy for patients with HER2+ gastric cancer/GEJC. These results support a further development of zanidatamab and tislelizumab with chemotherapy in this patient population in the ongoing phase III HERIZON-GEA-01 trial (NCT05152147).

Humans↗