Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients

Tang, Bixia; Yan, Xieqiao; Sheng, Xinan; Si, Lu; Cui, Chuanliang; Kong, Yan; Mao, Lili; Lian, Bin; Bai, Xue; Wang, Xuan; Li, Siming; Zhou, Li; Yu, Jiayi; Dai, Jie; Wang, Kai; Hu, Jinwei; Dong, Lei; Song, Haifeng; Wu, Hai; Feng, Hui; Yao, Sheng; Chen, Zhihong; Guo, Jun

doi:10.1186/s13045-018-0693-2

Cited by 114 publications

(101 citation statements)

References 32 publications

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“…NGS‐based ultra‐deep panel sequencing was performed on tumor samples and matched blood in a Clinical Laboratory Improvement Amendments–certified and College of American Pathologists–accredited laboratory (OrigiMed) . Briefly, genomic DNA from a formalin‐fixed paraffin‐embedded tissue specimen containing more than 20% tumor content was fragmented to ∼250 bp by sonication.…”

Section: Molecular Tumor Boardmentioning

confidence: 99%

A Rare EGFR–SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib

Li¹,

Zhang²,

Chen³

et al. 2019

The Oncologist

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Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Growing evidence supports gene fusions as good candidates for molecularly targeted therapy in CRC. Here we describe a case of a 63‐year‐old man who had a radical right hemicolectomy procedure 24 months ago. Pathological diagnosis indicated colorectal adenocarcinoma with stage pT4N2bMx. During re‐examination in December 2016, positron emission tomography/computed tomography scans indicated relapse with multiple lymph nodes metastasis. Then the patient received a nine‐cycle combination treatment of XELOX and bevacizumab and showed progressive disease (PD). Subsequently, the patient was treated with bevacizumab plus FOLFIRI for 2 months before discontinuation because of adverse events. Paraffin sections of postoperative colorectal tissue were subjected to next‐generation sequencing, and epidermal growth factor receptor (EGFR) amplification and rare EGFR–SEPT14 fusion were identified. The patient then received erlotinib, an EGFR tyrosine kinase inhibitor (TKI), and achieved a partial response. However, the patient subsequently showed PD, and a new variant, EGFRvIII, appeared in metastasis, which may be involved in erlotinib resistance. We suggest that there is value in treating patients harboring EGFR fusions with EGFR TKI therapy, and EGFR–SEPT14 fusion may be used as a therapeutic target for CRC. Key Points To the authors' knowledge, this is the first report of EGFR–SEPT14 fusion in colorectal cancer. The patient achieved a partial response after treatment with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. This report expands the list of gene fusions in colorectal cancer and highlights new targets for the therapeutic intervention. EGFRvIII may be involved in erlotinib resistance, which is rare in colorectal cancer.

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Section: Molecular Tumor Boardmentioning

confidence: 99%

A Rare EGFR–SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib

Li¹,

Zhang²,

Chen³

et al. 2019

The Oncologist

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“…They have demonstrated similar anti-cancer activities as those developed in the USA although some of them demonstrated higher in vitro binding affinity to the PD-1. Three of them have been approved for treating classical Hodgkin's lymphoma whereas one has been approved for treating melanoma [34][35][36][37][38][39][40]. None of them have been approved for more common types of malignancies such as NSCLC.…”

Section: Simple Addition: the Traditional Methods Of Combination Ici Dmentioning

confidence: 99%

Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy

et al. 2020

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Cancer immunotherapy has reached a critical point, now that immune checkpoint inhibitors and two CART products have received market approval in treating 16 types of cancers and 1 tissue-agnostic cancer indication. Accompanying these advances, the 2018 Nobel Prize was awarded for the discovery of immune checkpoint pathways, which has led to the revolution of anti-cancer treatments. However, expanding the indications of immuno-oncology agents and overcoming treatment resistance face mounting challenges. Although combination immunotherapy is an obvious strategy to pursue, the fact that there have been more failures than successes in this effort has served as a wake-up call, placing emphasis on the importance of building a solid scientific foundation for the development of next-generation immuno-oncology (IO) agents. The 2019 China Cancer Immunotherapy Workshop was held to discuss the current challenges and opportunities in IO. At this conference, emerging concepts and strategies for IO development were proposed, focusing squarely on correcting the immunological defects in the tumor microenvironment. New targets such as Siglec-15 and new directions including neoantigens, cancer vaccines, oncolytic viruses, and cytokines were reviewed. Emerging immunotherapies were discussed in the areas of overcoming primary and secondary resistance to existing immune checkpoint inhibitors, activating effector cells, and targeting immunosuppressive mechanisms in the tumor microenvironment. In this article, we highlight old and new waves of IO therapy development, and provide perspectives on the latest momentum shifts in cancer immunotherapy.

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“…The shift in focus from the direct targeting of the cancer cell towards the stimulation of the anti-tumor response has resulted in encouraging clinical results in humans, but also comes with new problems. Despite promising overall response rates (ORR) for treatment with CPIs, tumor vaccines and ACT or a combination of these, response rates to immunotherapy vary greatly between tumor subtypes, depending partly on their immunogenicities [30,[35][36][37][38][39][40][41][42][43][44]. Primary therapy resistance, defined as a lack of clinical benefit from immunotherapy on tumor growth, exists in a large proportion of patients.…”

Section: Limitations Of Immunotherapymentioning

confidence: 99%

Future Challenges in Cancer Resistance to Immunotherapy

Elsas

Hall

Burg

2020

Cancers

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Cancer immunotherapies, including checkpoint inhibitors, adoptive T cell transfer and therapeutic cancer vaccines, have shown promising response rates in clinical trials. Unfortunately, there is an increasing number of patients in which initially regressing tumors start to regrow due to an immunotherapy-driven acquired resistance. Studies on the underlying mechanisms reveal that these can be similar to well-known tumor intrinsic and extrinsic primary resistance factors that precluded the majority of patients from responding to immunotherapy in the first place. Here, we discuss primary and secondary immune resistance and point at strategies to identify potential new mechanisms of immune evasion. Ultimately, this may lead to improved immunotherapy strategies with improved clinical outcomes.

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Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients

Cited by 114 publications

References 32 publications

A Rare EGFR–SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib

A Rare EGFR–SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib

Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy

Future Challenges in Cancer Resistance to Immunotherapy

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