Investigational New Drugs最新文献

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Clinical features, treatment, and prognosis of pembrolizumab -induced Stevens-Johnson syndrome / toxic epidermal necrolysis. 派姆单抗诱导的Stevens-Johnson综合征/中毒性表皮坏死松解症的临床特征、治疗和预后
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2025-01-03 DOI: 10.1007/s10637-024-01499-z
Zhaoquan Wu, Xiting Li, Rui Huang, Binsheng He, Chunjiang Wang
{"title":"Clinical features, treatment, and prognosis of pembrolizumab -induced Stevens-Johnson syndrome / toxic epidermal necrolysis.","authors":"Zhaoquan Wu, Xiting Li, Rui Huang, Binsheng He, Chunjiang Wang","doi":"10.1007/s10637-024-01499-z","DOIUrl":"10.1007/s10637-024-01499-z","url":null,"abstract":"<p><p>The understanding of pembrolizumab-induced Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) primarily derives from case reports, leaving specific clinical features largely unknown. This study aims to investigate the clinical characteristics associated with pembrolizumab-induced SJS/TEN and to encourage the judicious use of pembrolizumab. Retrieve reports on pembrolizumab induced SJS/TEN before September 30, 2024 for retrospective analysis. Twenty-four (57.1%) and 18 (42.9%) patients were enrolled, with a median age of 65 years (range 32, 81). The median time to onset of SJS/TEN was 15 days (range 2, 180), and the median cycle was 1 cycle (range 1, 9). The most prevalent skin symptoms included erythema (66.7%), rash (64.3%), bullae/blisters (50.0%), and epidermal detachment (42.9%). Skin biopsy findings primarily revealed epidermal necrosis (42.9%), keratinocyte necrosis (35.7%), subepidermal bulla/blister (19.0%), and perivascular inflammatory cell infiltration (47.6%). Following the cessation of the drug and subsequent treatment, 85.7% of patients showed symptom improvement, while 14.3% succumbed to the condition. SJS/TEN represents a rare but potentially fatal adverse reaction to pembrolizumab. Clinicians should consider SJS/TEN in patients presenting with fever, erythematous rash, or mucosal involvement. Timely identification and management of SJS/TEN can significantly reduce morbidity and mortality.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"74-80"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630.
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2025-01-28 DOI: 10.1007/s10637-024-01504-5
Minhong Tang, John Crown, Michael J Duffy
{"title":"Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630.","authors":"Minhong Tang, John Crown, Michael J Duffy","doi":"10.1007/s10637-024-01504-5","DOIUrl":"10.1007/s10637-024-01504-5","url":null,"abstract":"<p><strong>Background: </strong>Since MYC is one of the most frequently altered driver genes involved in cancer formation, it is a potential target for new anti-cancer therapies. Historically, however, MYC has proved difficult to target due to the absence of a suitable crevice for binding potential low molecular weight drugs.</p><p><strong>Objective: </strong>The aim of this study was to evaluate a novel molecular glue, dubbed GT19630, which degrades both MYC and GSPT1, for the treatment of breast cancer.</p><p><strong>Methods: </strong>The antiproliferative potential of GT19630 was evaluated in 14 breast cancer cell lines representing the main molecular subtypes of breast cancer. In addition, we also investigated the effects of GT19630 on apoptosis, cell cycle progression, cell migration, and degradation of the negative immune checkpoint protein, B7-H3.</p><p><strong>Results: </strong>GT19630 inhibited cell proliferation, blocked cell cycle progression, promoted apoptosis, and decreased cell migration at low nanomolar concentrations in breast cancer cell lines. By contrast, previously described MYC inhibitors such as specific MYC-MAX antagonists affected these processes at micromolar concentrations. Consistent with the ability of MYC to promote immune evasion, we also found that GT19630 degraded the negative immune checkpoint inhibitor, B7-H3.</p><p><strong>Conclusions: </strong>We conclude that the novel molecular glue, GT19630, is a potent mediator of endpoints associated with cancer formation/progression. Its ability to degrade B7-H3 suggests that GT19630 may also promote host immunity against cancer. To progress GT19630 as a therapy for breast cancer, our finding should now be confirmed in an animal model system.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"167-179"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA. 根据循环肿瘤DNA的基线遗传改变,奥西替尼治疗treatment-naïve egfr突变的非小细胞肺癌的分期特异性疗效
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2025-01-09 DOI: 10.1007/s10637-024-01500-9
Yoshihiko Taniguchi, Akihiro Tamiya, Mitsuo Osuga, Shun-Ichi Isa, Keiichi Nakamura, Yasuyuki Mizumori, Tsutomu Shinohara, Hidetoshi Yanai, Katsumi Nakatomi, Masahide Oki, Masahide Mori, Tomohito Kuwako, Koji Yamazaki, Masahiro Shimada, Masahiko Ando, Yasuhiro Koh
{"title":"Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA.","authors":"Yoshihiko Taniguchi, Akihiro Tamiya, Mitsuo Osuga, Shun-Ichi Isa, Keiichi Nakamura, Yasuyuki Mizumori, Tsutomu Shinohara, Hidetoshi Yanai, Katsumi Nakatomi, Masahide Oki, Masahide Mori, Tomohito Kuwako, Koji Yamazaki, Masahiro Shimada, Masahiko Ando, Yasuhiro Koh","doi":"10.1007/s10637-024-01500-9","DOIUrl":"10.1007/s10637-024-01500-9","url":null,"abstract":"<p><p>The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations. We compared the progression-free survival (PFS), overall survival (OS), and pretreatment co-occurring genetic alterations detected in plasma between patients with stages IVA (n = 83) and IVB disease (n = 84). Multivariate analysis of PFS and OS revealed that stage IVB was associated with a poor prognosis (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.36-3.04, p < 0.001, HR: 2.35, 95% CI: 1.45-3.90, p < 0.001, respectively). Pre-osimertinib treatment, significantly more TP53- (52.4% vs. 27.7%, p = 0.002), EGFR amplification- (58.3% vs. 23.2%, p < 0.001), and MET amplification-positive cases (22.6% vs. 7.2%, p = 0.008) were found among stage IVB than among stage IVA or lower cases. Patients with EGFR-positive NSCLC in stage IVB exhibited significantly shorter PFS and OS than those in earlier stages when treated with first-line osimertinib. The prevalence of baseline TP53 mutations, EGFR amplification, and MET amplification in plasma were significantly higher in stage IVB cases, implicating them in the worse outcomes of this group.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"101-107"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Linifanib alone and in combination with metronomic chemotherapy is active on cutaneous T-cell lymphoma cells by targeting the AKT/mTOR signaling pathway. 利尼法尼单用和联合节律化疗通过靶向AKT/mTOR信号通路对皮肤t细胞淋巴瘤细胞有活性。
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2025-01-17 DOI: 10.1007/s10637-024-01501-8
Marta Banchi, Maria Christina Cox, Arianna Bandini, Paola Orlandi, Costanza Tacchi, Fabio Stefanelli, Silvio Chericoni, Guido Bocci
{"title":"Linifanib alone and in combination with metronomic chemotherapy is active on cutaneous T-cell lymphoma cells by targeting the AKT/mTOR signaling pathway.","authors":"Marta Banchi, Maria Christina Cox, Arianna Bandini, Paola Orlandi, Costanza Tacchi, Fabio Stefanelli, Silvio Chericoni, Guido Bocci","doi":"10.1007/s10637-024-01501-8","DOIUrl":"10.1007/s10637-024-01501-8","url":null,"abstract":"<p><p>Cutaneous T-cell lymphomas (CTCLs) are a rare and heterogeneous subset of skin-localized, non-Hodgkin lymphomas. Our aim was to evaluate the in vitro antitumor activity of the multi-kinase inhibitor linifanib, either alone or in combination with metronomic vinorelbine (mVNR) or etoposide (mETO), on CTCL cells. In vitro proliferation assay and Luminex analysis showed that long-term, daily exposure of linifanib significantly inhibited the proliferation of the human CTCL cell line HH, in a concentration-dependent manner (IC<sub>50</sub> = 48.4 ± 20.4 nM) and the phosphorylation of AKT/mTOR signaling pathway. The concomitant exposure of linifanib plus mVNR or mETO resulted in a strong synergism, with combination index values < 1. Linifanib significantly increased the VNR and ETO intracellular concentrations in HH cells, evaluated by UPLC-HRMS technology, and strongly reduced the ABCB1 and ABCG2 gene expression in HH. In conclusion, we reported a striking antitumor activity of daily, long-term linifanib and a clear synergistic effect when administered in combination with mCHEMO on CTCL cells, as a promising base for future clinical approaches in T-cell lymphomas.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"135-146"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lenvatinib plus immunotherapy versus lenvatinib monotherapy in lenvatinib-insensitive patients with unresectable hepatocellular carcinoma: a retrospective study.
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2025-01-07 DOI: 10.1007/s10637-024-01502-7
Zeyu Yu, Bin Leng, Ran You, Chendong Wang, Lingfeng Diao, Qingyu Xu, Guowen Yin
{"title":"Lenvatinib plus immunotherapy versus lenvatinib monotherapy in lenvatinib-insensitive patients with unresectable hepatocellular carcinoma: a retrospective study.","authors":"Zeyu Yu, Bin Leng, Ran You, Chendong Wang, Lingfeng Diao, Qingyu Xu, Guowen Yin","doi":"10.1007/s10637-024-01502-7","DOIUrl":"10.1007/s10637-024-01502-7","url":null,"abstract":"<p><strong>Purpose: </strong>The combination therapy of lenvatinib and immunotherapy as first-line treatment remains controversial in unresectable hepatocellular carcinoma (uHCC). This research aimed to compare the efficacy and safety of lenvatinib monotherapy (L) and combination therapy of lenvatinib and immune checkpoint inhibitor (LI) in lenvatinib-insensitive patients with uHCC.</p><p><strong>Methods: </strong>Two hundred fifty-five uHCC patients were enrolled in this study. Patients were classified into two groups: (1) Lenvatinib monotherapy (L); (2) Combination therapy (LI). Patients who remained stable disease (SD) but did not achieve complete response (CR) or partial response (PR) or progression disease (PD) for at least 3 months after receiving lenvatinib monotherapy were defined as lenvatinib-insensitive. Overall survival (OS) and progression-free survival (PFS), baseline characteristics, and safety were compared between groups.</p><p><strong>Results: </strong>The LI group had longer OS (15.9 months vs. 11.9 months, P = 0.001) and PFS (12.6 months vs. 7.3 months, P < 0.001) than the L group. ECOG PS was an independent prognostic factor affecting OS and Up-to-seven was an independent prognostic factor affecting PFS. The frequency of grade ≥ 3 treatment-related adverse events (TRAEs) was not significantly different.</p><p><strong>Conclusions: </strong>Our study demonstrated that the combination therapy (LI) had longer OS and PFS than the lenvatinib monotherapy (L) in lenvatinib-insensitive patients with uHCC.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":"43 1","pages":"93-100"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dual PTCH2 mutation [Ser391*, Leu104Pro]: unveiling a potential new genetic susceptibility factor for glioma development. PTCH2 双突变[Ser391*, Leu104Pro]:揭示胶质瘤发展的潜在新遗传易感因素。
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2025-01-13 DOI: 10.1007/s10637-024-01491-7
Xiang Li, Yingting Wu, Tiantian Han, Ran Ding, Rongrong Kong, Siqi Chen, Ningning Luo, Mingji Jin, Dongsheng Chen, Ping Zhang
{"title":"Dual PTCH2 mutation [Ser391*, Leu104Pro]: unveiling a potential new genetic susceptibility factor for glioma development.","authors":"Xiang Li, Yingting Wu, Tiantian Han, Ran Ding, Rongrong Kong, Siqi Chen, Ningning Luo, Mingji Jin, Dongsheng Chen, Ping Zhang","doi":"10.1007/s10637-024-01491-7","DOIUrl":"10.1007/s10637-024-01491-7","url":null,"abstract":"<p><p>Gliomas are a heterogeneous type of central nervous system tumor. The etiology of glioma formation remains elusive, with approximately 5% of gliomas being familial, underscoring the significance of understanding genetic susceptibility in glioma development. In this study, a dual germline PTCH2 mutation [Ser391*, Leu104Pro] was identified in a family with a history of glioma, and sequencing data from WES/SimcereDx Neuro-Onco 360 including 910 Chinese patients with glioma and 1666 patients with solid tumors were analyzed. A potential link between PTCH2 mutations and glioma development was observed in the Chinese population. Comprehensive analysis revealed that gliomas harboring dual PTCH2 mutations were segregated into two distinct clinical subtypes, indicating that the presence of PTCH2 is a novel genetic risk factor for glioma. These findings expand the genetic risk profile of glioma and offer promising avenues for the development of targeted diagnostic and therapeutic strategies. The results of this study emphasize the necessity for a comprehensive investigation into the genetic predisposition to gliomas, particularly in Asian populations, to achieve a better understanding of and management strategy for this complex disease.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"126-134"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer. OxPhos抑制剂ME-344联合贝伐单抗治疗难治性转移性结直肠癌的1b期研究
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2024-12-27 DOI: 10.1007/s10637-024-01489-1
Patrick M Boland, Heinz-Josef Lenz, Kristen K Ciombor, Vaia Florou, Michael J Pishvaian, Michael Cusnir, Deirdre Cohen, Jessie Y Guo, Min Tang, Prabhu Rajagopalan, Sandra E Wiley, Richard G Ghalie, Howard S Hochster
{"title":"A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer.","authors":"Patrick M Boland, Heinz-Josef Lenz, Kristen K Ciombor, Vaia Florou, Michael J Pishvaian, Michael Cusnir, Deirdre Cohen, Jessie Y Guo, Min Tang, Prabhu Rajagopalan, Sandra E Wiley, Richard G Ghalie, Howard S Hochster","doi":"10.1007/s10637-024-01489-1","DOIUrl":"10.1007/s10637-024-01489-1","url":null,"abstract":"<p><p>Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC). Patients were eligible if they had disease progression after standard therapies, adequate hematologic, hepatic and renal function, and no contraindications to bevacizumab. ME-344 was administered intravenously on days 1, 8 and 15 and bevacizumab on days 1 and 15 of 28-day cycles until disease progression or intolerance. The primary efficacy endpoint was progression-free survival (PFS) at week 16. In the 23 patients enrolled, the median age was 58 years, median number of prior lines of therapy was 4, and median interval from last therapy was 3 months. The most common adverse events (all grades/grade ≥ 3) were fatigue (48%/13%), abdominal pain (35%/4%), diarrhea (30%/4%) and constipation (30%/0%). No patient had an objective response; 9 patients (39%) achieved stable disease. The 16-week PFS was 30.6% (95% confidence interval [CI]: 12.2-51.3), the median PFS was 1.9 months (95% CI: 1.6-4.7), and the median overall survival was 6.7 months (95% CI: 3.4-not reached). ME-344 plus bevacizumab was well tolerated. Disease control was limited in this heavily pretreated patient population. Additional investigations in earlier lines are indicated, and extended-release ME-344 formulations may provide longer drug exposure to maximize benefit. (Trial registration number ClinicalTrials.gov NCT05824559. Registration date 22 March 2022).</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"60-68"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of the combination of envafolimab and lenvatinib in unresectable hepatocellular carcinoma: a single-arm, multicentre, exploratory phase II clinical study. envafolimab和lenvatinib联合治疗不可切除肝细胞癌的疗效和安全性:单臂、多中心、探索性II期临床研究
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2024-12-17 DOI: 10.1007/s10637-024-01468-6
Yi Jiang, Ke Su, Han Li, Chenjie Wang, Zhenying Wu, Jiali Chen, Zhiyao Zhang, Kun He, Yunwei Han
{"title":"Efficacy and safety of the combination of envafolimab and lenvatinib in unresectable hepatocellular carcinoma: a single-arm, multicentre, exploratory phase II clinical study.","authors":"Yi Jiang, Ke Su, Han Li, Chenjie Wang, Zhenying Wu, Jiali Chen, Zhiyao Zhang, Kun He, Yunwei Han","doi":"10.1007/s10637-024-01468-6","DOIUrl":"10.1007/s10637-024-01468-6","url":null,"abstract":"<p><p>Currently, therapeutic combinations of immune checkpoint inhibitors (ICIs) with anti-angiogenic agents have shown promising outcomes and have the potential to establish a new standard of care. The efficacy and safety of the first-line combination of envafolimab (an ICI) and lenvatinib (an anti-tumor angiogenesis drug) for the treatment of patients with inoperable hepatocellular carcinoma (HCC) have not been demonstrated. Unresectable HCC patients with an Eastern Cooperative Oncology Group (ECOG) physical status score ≤ 1 and a Child-Pugh score ≤ 7 who had not received systemic therapy were included in this single-arm, exploratory, multicentre phase II clinical study. All patients were required to meet the criteria of being at least 18 years of age, having no history of other malignancies, and existing at least one measurable lesion. The patients were treated with envafolimab (150 mg, QW, subcutaneous) in combination with lenvatinib (12 mg for patients weighing over 60 kg, 8 mg for patients weighing under 60 kg). The co-primary endpoint of the study was overall survival (OS), while surrogate endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Between March 2022 and April 2023, 36 patients were enrolled, 30 of whom were treated with envafolimab plus lenvatinib. At data cutoff, the median follow-up duration was 20 months (95% CI 18.9-21.1). Among the 30 assessable patients (patients treated according to the trial protocol), the median overall survival (mOS) and median progression-free survival (mPFS) for the therapy comprising envafolimab alongside lenvatinib were 18.5 months (95% CI 13.2-23.8) and 9.4 months (95% CI 1.6-15.6), respectively. The ORR and the DCR (evaluated according to mRECIST criteria) reached 40% and 80%, respectively. In terms of safety, 23 patients (76.7%) experienced at least one treatment-related adverse event (TRAE), of which the most common was elevated aspartate aminotransferase (AST, 23.3%). Furthermore, grade 3 and higher TRAEs occurred in 30%. This study demonstrates that envafolimab in combination with lenvatinib exhibits favourable anti-cancer activity and a manageable safety profile for the first-line treatment of patients with unresectable HCC.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"18-29"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic antitumor effect of MK-1775 and CUDC-907 against prostate cancer. MK-1775 和 CUDC-907 对前列腺癌的协同抗肿瘤作用
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2025-01-27 DOI: 10.1007/s10637-024-01490-8
Saisai Ma, Yichen Xu, Minmin Liu, Shuaida Wu, Ye Zhang, Hongyan Xia, Ji Lu, Yang Zhan
{"title":"Synergistic antitumor effect of MK-1775 and CUDC-907 against prostate cancer.","authors":"Saisai Ma, Yichen Xu, Minmin Liu, Shuaida Wu, Ye Zhang, Hongyan Xia, Ji Lu, Yang Zhan","doi":"10.1007/s10637-024-01490-8","DOIUrl":"10.1007/s10637-024-01490-8","url":null,"abstract":"<p><p>Due to the emergence of drug resistance, androgen receptor (AR)-targeted drugs still pose great challenges in the treatment of prostate cancer, and it is urgent to explore an innovative therapeutic strategy. MK-1775, a highly selective WEE1 inhibitor, is shown to have favorable therapeutic benefits in several solid tumor models. Recent evidence suggests that the combination of MK-1775 with DNA-damaging agents could lead to enhanced antitumor efficacy. Here, our results demonstrate that MK-1775 alone could indeed inhibit proliferation and induce apoptosis in prostate cancer. Moreover, the combination of MK-1775 and a dual PI3K and HDAC inhibitor, CUDC-907, can synergistically inhibit cell proliferation and dramatically induces apoptosis in prostate cancer cells. This effect is partially mediated by DNA damage, resulting from the downregulation of DNA damage response (DDR) proteins such as CDK, CHK, and RRM1/2. Notably, the combination of MK-1775 and CUDC-907 leads to significant antitumor effects in vivo. Our findings provide a strong basis for a promising combination strategy against prostate cancer.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"157-166"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical features, treatment, and outcomes of nivolumab induced psoriasis. 纳武单抗诱导银屑病的临床特征、治疗和结局。
IF 3 3区 医学
Investigational New Drugs Pub Date : 2025-02-01 Epub Date: 2024-12-26 DOI: 10.1007/s10637-024-01494-4
Shaoli Zhao, Wei Sun, Jichun Sun, Liping Peng, Chunjiang Wang
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