Clinical Cancer Research最新文献

{"title":"Genomic biomarkers predict response to combined ATR inhibition and radiotherapy.","authors":"Benjamin R Schrank,Lauren E Colbert","doi":"10.1158/1078-0432.ccr-24-2306","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2306","url":null,"abstract":"For decades, chemoradiosensitization with checkpoint kinase inhibitors has been proposed but largely unexplored. A recent study reports the novel ATR kinase inhibitor, RP-3500, synergizes with radiation to control Atm-/- tumors in vivo. RP-3500 did not radiosensitize wild-type or Brca-1 deficient tumors, highlighting the need for a genotype-tailored approach.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SWOG/NCI Phase II Dual Anti-CTLA-4/PD-1 Blockade in Rare Tumors (DART): Non-Epithelial Ovarian Cancer.","authors":"Young Kwang Chae,Megan Othus,Sandip Pravin Patel,Kelly J Wilkinson,Emily M Whitman-Purves,Jayanthi Lea,John M Schallenkamp,Nabil Adra,Leonard J Appleman,Mitchell Alden,Jessica Thomes Pepin,John A Ellerton,Andrew Poklepovic,Adam Walter,Murtuza M Rampurwala,William R Robinson,Hye Sung Kim,Liam Il-Young Chung,Christine M McLeod,Gabby Lopez,Helen X Chen,Elad Sharon,Howard Streicher,Christopher W Ryan,Charles D Blanke,Razelle Kurzrock","doi":"10.1158/1078-0432.ccr-24-0606","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-0606","url":null,"abstract":"BACKGROUNDThe role of dual checkpoint inhibition in advanced rare/ultra-rare non-epithelial ovarian cancers (NEOCs) is yet to be explored.METHODSDART is a prospective, multicenter (1,016 US sites), multi-cohort, single-arm phase II trial conducted through the Early Therapeutics and Rare Cancer SWOG/NCI Committee, assessing ipilimumab (anti-CTLA-4) (1mg/kg every 6 weeks) and nivolumab (anti-PD-1) (240mg every 2 weeks) in adults with advanced NEOCs who lack beneficial standard therapy. Primary outcome was overall response rate [ORR; complete response (CR)/partial response (PR)]; secondary outcomes were progression-free survival (PFS), overall survival (OS), clinical benefit rate [CBR; stable disease (SD) ≥6 months plus ORR], and toxicity.RESULTSSeventeen patients (median age: 64; number of prior therapies ranged from 0-8 with no immunotherapy exposure; 8 granulosa, 6 carcinosarcomas, 1 Sertoli-Leydig, 1 yolk sac, 1 Wolffian) were evaluated. In granulosa cell tumors, ORR was 25% (n=2/8; 1 CR, 1 PR) and CBR, 50% (n=4/8); PFS of 58.3 (CR), 50.7+ (PR), 30.4 (SD), and 8.7 (SD) months. Median PFS was 3.5 months (95% confidence intervals (CI) 1.7-11.2 months); median OS, 42.5 months (95% CI 10.1 months-not reached). One Sertoli-Leydig cell tumor showed a 22% regression (PFS 11.2 months). Carcinosarcomas had no response. Three participants (18%) discontinued treatment due to grade 3-4 adverse events.CONCLUSIONSIpilimumab-nivolumab shows activity in treatment-refractory granulosa cell tumors, with 25% (n=2/8) of patients experiencing either CR or PR lasting over 4 years..","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant intratumoral plasmid interleukin-12 electro-gene-transfer and nivolumab in patients with operable locoregionally advanced melanoma.","authors":"Ahmad A Tarhini,Zeynep Eroglu,Islam Eljilany,Jonathan S Zager,Ricardo J Gonzalez,Amod A Sarnaik,C Wayne Cruse,Nikhil I Khushalani,Deanryan B De Aquino,Edith Abraham,Diana M Acevedo,Allison Richards,Michael J Schell,Denise Kalos,Pei-Ling Chen,Jane L Messina,David A Canton,Vernon K Sondak","doi":"10.1158/1078-0432.ccr-24-2768","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2768","url":null,"abstract":"PURPOSEIntratumoral (IT) TAVO-EP (tavokinogene telseplasmid delivered by electroporation) results in localized expression of interleukin-12 (IL-12) within the tumor microenvironment (TME). This study evaluated neoadjuvant TAVO-EP combined with intravenous (IV) nivolumab followed by surgery and adjuvant nivolumab in patients with operable locoregionally advanced melanoma.PATIENTS AND METHODSThe neoadjuvant phase comprised up to 3 Χ 4-week cycles where TAVO-EP was given IT on days 1, 8, and 15 (optional) concurrently with 480 mg nivolumab IV on day 8 of each 4-week cycle. Surgery followed, and adjuvant nivolumab was initiated after surgery. The primary endpoint was pathologic complete response (pCR). Secondary endpoints included major pathological response (MPR; pCR or near pCR).RESULTSSixteen patients were enrolled and the preoperative radiological response rate was 63%. One patient declined surgery after experiencing a significant clinical response. Among the remaining 15 patients, pCR rate was 60% and MPR was 80%. No patient with MPR has had disease recurrence with a median follow-up from the date of surgery of 15.4 months. At baseline, most patients exhibited low CD8+ TIL, PD-L1 and IFN-γ gene expression signature. There was enhanced immune activation following treatment in the TME and blood including increased immune-related gene expression, CD8+ TIL and proliferating immune cell subsets.CONCLUSIONSThe clinical efficacy of neoadjuvant IT TAVO-EP + nivolumab is promising with 80% of patients achieving an MPR. Evidence of potent immune activation both systemically and within the TME along with a favorable safety profile supports the activity of local IL-12 and anti-PD1 based regimens.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Dynamics of T and B Cell Response Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma.","authors":"Yutaka Kurebayashi,Katsutoshi Sugimoto,Hanako Tsujikawa,Kosuke Matsuda,Rui Nomura,Akihisa Ueno,Yohei Masugi,Ken Yamazaki,Kathryn Effendi,Hirohito Takeuchi,Takao Itoi,Yasushi Hasegawa,Yuta Abe,Minoru Kitago,Hidenori Ojima,Michiie Sakamoto","doi":"10.1158/1078-0432.ccr-24-0479","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-0479","url":null,"abstract":"PURPOSEImmunotherapies have led to a paradigm shift in the treatment of hepatocellular carcinoma (HCC). Studies have revealed the single-cell catalogues of tumor-infiltrating immune cells and the trajectories of their differentiation. Nevertheless, the spatial distribution of these immune cells with distinct phenotypes in tumor microenvironment and their clinicopathological significance in resectable and unresectable HCCs are still largely unclear.EXPERIMENTAL DESIGNWe analyzed the spatial dynamics of intratumoral CD4 and CD8 T cells and their association with B and plasma cells using 283 surgically resected HCCs, 58 unresectable HCC samples before combined immunotherapy (atezolizumab plus bevacizumab [Atezo+Bev]), and autopsy specimens from 50 cases of advanced-stage HCCs through multiplex immunohistochemistry combined with transcriptomic and driver gene mutation analysis. Classification based on the spatial dynamics of T and B cell responses (refined immunosubtype) was developed and its clinicopathological significance was analyzed.RESULTSWe found that stem-like CD4 and CD8 T cells were mainly observed in T cell aggregates. Differentiation of T follicular helper cells were associated with the development of tertiary lymphoid structures, whereas differentiation of CD4 TCXCL13 cells with phenotype resembling T peripheral helper cells were associated with the development of lymphoplasmacytic microenvironment. The refined immunosubtype could predict clinical outcomes of resectable HCC after surgery and unresectable HCC after Atezo+Bev therapy. The immune microenvironment of metastatic lesions tended to reflect those of primary lesions.CONCLUSIONSWe revealed the spatial dynamics of T and B cell response in HCC, which is closely associated with the clinical outcome after surgical resection or Atezo+Bev therapy.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic landscape of circulating tumor DNA and real-world outcomes in advanced endometrial cancer.","authors":"Pamela Soberanis Pina,Keelia Clemens,Adrian Bubie,Brooke Grant,Ginger Haynes,Nicole Zhang,Leylah Drusbosky,Stephanie Lheureux","doi":"10.1158/1078-0432.ccr-24-2105","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2105","url":null,"abstract":"PURPOSEctDNA is a novel technique extensively studied in solid tumors, although not currently well defined in endometrial cancer (EC).EXPERIMENTAL DESIGNA de-identified retrospective analysis of 1988 patients with advanced/recurrent EC was performed. In addition, an analysis of a real-world evidence (RWE) cohort was completed (n=1266). Patients underwent ctDNA testing using Guardant360 during routine clinical care. The objective was to describe and assess molecular landscape using ctDNA.RESULTSAmong 1988 ctDNA samples, at least one somatic alteration was detected in 91.6% (n=1821). Most frequently altered genes were TP53 (64%), PIK3CA (29%), PTEN (25%), ARID1A (20%) and KRAS (14%). Overall, 18.5% had amplifications, with the majority identified in CCNE1 (40.9%), PIK3CA (22%) and EGFR (19.3%). From the RWE cohort, those with TP53 mutations had a worse overall survival (OS) vs those without TP53 mutations (p=0.02) and those with TP53 co-mutations had an inferior OS in comparison to TP53-mutated only (p=0.016). Amongst these, patients with a PIK3CA co-mutation (p=0.012) and CCNE1 amplification (p=0.01) had inferior OS compared to those with only TP53 mutations. 57 patients with newly diagnosed EC had at least 2 serial ctDNA samples showing evolution in detected variants compared to baseline samples, with TP53 being the most frequent change.CONCLUSIONSThis study is one of the largest cohorts of ctDNA currently reported in EC. The presence of TP53 mutation and other co-mutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for EC.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes.","authors":"Sushant Patkar,Joshua Mannheimer,Stephanie A Harmon,Christina J Ramirez,Christina N Mazcko,Peter L Choyke,G Thomas Brown,Baris Turkbey,Amy K LeBlanc,Jessica A Beck","doi":"10.1158/1078-0432.ccr-24-1854","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1854","url":null,"abstract":"PURPOSEOsteosarcoma is an aggressive bone cancer lacking robust biomarkers for personalized treatment. Despite its scarcity in humans, it is relatively common in adult pet dogs. This study aimed to analyze clinically annotated bulk tumor transcriptomic datasets of canine and human osteosarcoma patients to identify potentially conserved patterns of disease progression.EXPERIMENTAL DESIGNBulk transcriptomic data from 245 pet dogs with treatment-naïve appendicular osteosarcoma were analyzed using deconvolution to characterize the tumor microenvironment (TME). The TME of both primary and metastatic tumors derived from the same dog was compared, and its impact on canine survival was assessed. A machine learning model was developed to classify the TME based on its inferred composition using canine tumor data. This model was applied to 8 independent human osteosarcoma datasets to assess its generalizability and prognostic value.RESULTSThis study found three distinct TME subtypes of canine osteosarcoma based on cell type composition of bulk tumor samples: Immune Enriched (IE), Immune Enriched Dense Extra-Cellular Matrix-like (IE-ECM), and Immune Desert (ID). These three TME-based subtypes of canine osteosarcomas were conserved in humans and could predict progression-free survival outcomes of human patients, independent of conventional prognostic factors such as percent tumor necrosis post standard of care chemotherapy treatment and disease stage at diagnosis.CONCLUSIONSThese findings demonstrate the potential of leveraging data from naturally occurring cancers in canines to model the complexity of the human osteosarcoma TME, offering a promising avenue for the discovery of novel biomarkers and developing more effective precision oncology treatments.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor hypoxia: long ignored but now detectable and potentially actionable.","authors":"Ralph P Mason","doi":"10.1158/1078-0432.ccr-24-2626","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2626","url":null,"abstract":"Oxygen-enhanced MRI was successfully applied to 24 patients with HPV-associated oropharyngeal cancer. This prospective trial rigorously evaluated reproducibility and changes with respect to tumor radiation. Analyses compared hypoxic volumes and hypoxic fractions. It represents important progress in developing a practical approach to assessing tumor hypoxia in patients noninvasively.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDA Approval Summary: Teclistamab - A Bispecific CD3 T-cell Engager for Patients with Relapsed or Refractory Multiple Myeloma.","authors":"Andrea C Baines,Bindu Kanapuru,Jay Zhao,Lauren S L Price,Nan Zheng,Robyn Konicki,Michael L Manning,Brenda J Gehrke,Marc R Theoret,Nicole J Gormley","doi":"10.1158/1078-0432.ccr-24-1872","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1872","url":null,"abstract":"On October 25, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to teclistamab-cqyv (TECVAYLI; Janssen Biotech) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. Substantial evidence of effectiveness was obtained from the MajesTEC-1 trial, a phase 1/2, single-arm, open-label, multi-center study. Patients received step-up doses of teclistamab at 0.06 mg/kg and 0.3 mg/kg followed by 1.5 mg/kg subcutaneously once weekly until disease progression or unacceptable toxicity. An overall response rate of 61.8% was observed, with a complete response or better rate of 28.2%. Cytokine release syndrome (CRS) occurred in 72% of patients and neurologic toxicity (NT) occurred in 57%, including immune effector cell-associated neurotoxicity syndrome (ICANS) in 6%. Due to the risk of CRS and NT, including ICANS, the U.S. prescribing information for teclistamab includes a boxed warning and teclistamab is available only through a restricted program under a risk evaluation and mitigation strategy. Here, we summarize the data and FDA review supporting the accelerated approval of teclistamab, a BCMA-directed bispecific antibody that was the first bispecific CD3 T-cell engager approved for treatment of multiple myeloma.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Heterogeneity of EGFR-Mutant Non-Small Cell Lung Cancer Evolution Toward Small-Cell Lung Cancer.","authors":"Songji Oh, Jaemoon Koh, Tae Min Kim, Soyeon Kim, Jeonghwan Youk, Miso Kim, Bhumsuk Keam, Yoon Kyung Jeon, Ja-Lok Ku, Dong-Wan Kim, Doo Hyun Chung, Dae Seog Heo","doi":"10.1158/1078-0432.CCR-24-0160","DOIUrl":"10.1158/1078-0432.CCR-24-0160","url":null,"abstract":"<p><strong>Purpose: </strong>Histologic transformation from EGFR-mutant non-small cell lung cancer (NSCLC) to small-cell lung cancer (SCLC) is a key mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI). However, transcriptomic changes between NSCLC and transformed SCLC (t-SCLC) remain unexplored.</p><p><strong>Experimental design: </strong>We conducted whole-transcriptome analysis of 59 regions of interest through the spatial profiling of formalin-fixed, paraffin-embedded tissues obtained from 10 patients (lung adenocarcinoma, 22; combined SCLC/NSCLC, 7; and t-SCLC, 30 regions of interests). Transcriptomic profiles and differentially expressed genes were compared between pre- and post-transformed tumors.</p><p><strong>Results: </strong>Following EGFR-TKI treatment, 93.7% (15/16) of t-SCLC components evolved into neuroendocrine-high subtypes (SCLC-A or SCLC-N). The transition to t-SCLC occurred regardless of EGFR-TKI treatment and EGFR mutational status, with a notable decrease in EGFR expression (P < 0.001) at both mRNA and protein levels. Pathway analysis revealed that gene overexpression was related to epigenetic alterations in t-SCLC. Interestingly, histone deacetylase inhibitors restored EGFR expression in SNU-2962A cells and their organoid model. The synergistic effects of third-generation EGFR-TKI osimertinib and the histone deacetylase inhibitor fimepinostat were validated in both in vitro and in vivo models.</p><p><strong>Conclusions: </strong>Our study demonstrated that most t-SCLC cases showed neuronal subtypes with low EGFR expression. Differentially expressed gene analysis and t-SCLC preclinical models identified an epigenetic modifier as a promising treatment strategy for t-SCLC.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histology-specific clinical trial of lenvatinib and pembrolizumab in patients with sarcoma","authors":"Sujana Movva, Kenneth Seier, Viswatej Avutu, Lauren B. Banks, Jason Chan, Ping Chi, Mark A. Dickson, Mrinal M. Gounder, Ciara M. Kelly, Mary L. Keohan, Robert Maki, Evan Rosenbaum, Tiffany Salcito, Kaithleen Rodriguez, Rebecca Dempsey, Paul A. Meyers, Seth M. Cohen, Martee L. Hensley, Jason A. Konner, Alison M. Schram, Robert A. Lefkowitz, Joseph P. Erinjeri, Li-Xuan Qin, William D. Tap, Sandra P. D'Angelo","doi":"10.1158/1078-0432.ccr-24-2519","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2519","url":null,"abstract":"Purpose: Survival of patients with metastatic sarcoma remains poor, and there is pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multi-receptor tyrosine kinase inhibitor targeting tumor vasculature, has immunomodulatory activity that contributes to its antitumor effects. Therefore we hypothesized that combination of lenvatinib and pembrolizumab would lead to improved clinical outcomes in patients with sarcoma. Methods: This was an open-label, single-arm study of lenvatinib and pembrolizumab in the following cohorts A: leiomyosarcoma, B: undifferentiated pleomorphic sarcoma (UPS), C: vascular sarcomas (angiosarcoma and epithelioid hemangioendothelioma), D: synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST), and E: bone sarcomas (osteosarcoma and chondrosarcoma). The primary endpoint was best overall response (BOR) rate documented by RECIST v1.1 by 27 weeks in each cohort, with a threshold of ≥2 responses among 10 patients. Secondary endpoints included progression-free survival, overall survival, duration of response and safety. Results: Forty-six patients were evaluable for the primary endpoint which was met in the UPS and MPNST/synovial cohorts (BOR rates by 27 weeks of 25% and 30%,respectively). There were 7 partial responses overall with additional responses noted in angiosarcoma and osteosarcoma. Treatment-related adverse events of any grade, and Grade 3 or higher, occurred in 50/51 (98%) and 29/51 (57%) of patients respectively. Conclusions: We observed durable responses in MPNST, synovial sarcoma and osteosarcoma. Patients with UPS and angiosarcoma also responded. Further exploration of this approach is warranted to confirm activity and determine optimal dosing schedules.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}