43P MRTX-500: Phase II trial of sitravatinib (sitra) + nivolumab (nivo) in patients (pts) with non-squamous (NSQ) non-small cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy

Leal, Ticiana; Berz, David; Rybkin, Igor I.; Iams, Wade T.; Bruno, Débora S.; Blakely, Collin M.; Spira, Alexander I.; Patel, Manish R.; Waterhouse, David; Richards, Donald A.; Pham, Anthony; Jotte, Robert M.; Garon, E.B.; Hong, D.S.; Shazer, R.; Yan, Xiaohong; Latven, L.; He, Kai

doi:10.1016/j.annonc.2022.01.052

Cited by 13 publications

(9 citation statements)

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“…Therefore, sitravatinib can lead to changes in innate and adaptive immune cells, thereby enhancing the immune checkpoint blockade. In an open-label clinical phase II study (MRTX-500) ( 29 ), sitravatinib in combination with nivolumab showed good clinical efficacy in patients with non-squamous NSCLC whose disease progressed on previous anti-PD-1/L1 regimen, with a primary endpoint objective response rate (ORR) of 18% (12/68), median progression-free-survival (mPFS) of 5.7 months, and median overall survival (mOS) of 14.9 months. Sitravatinib in combination with nivolumab showed better anti-tumor activity and OS than did the control in previous studies, with no new safety signals observed.…”

Section: Immunotherapeutic Strategies Targeting the Tmementioning

confidence: 99%

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Bai

Cui

2022

Front. Immunol.

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Tumor immune microenvironment is a very complex system that is influenced by a wide range of factors; in this microenvironment, various immune cells, stromal cells, and cytokines can interact with tumor cells and jointly regulate this complex ecosystem. During tumor development, the tumor microenvironment (TME) shows the upregulation of inhibitory signals and downregulation of activating signals, which result in an immunosuppressive microenvironment and lead to tumor immune escape. In recent years, a variety of precision immunotherapy strategies have been developed to remodel the TME into a positive immune microenvironment by stimulating or restoring the inherent tumor inhibition ability of the immune system so as to improve anti-tumor therapeutic efficacy. This review focuses on immunotherapy strategies targeting the TME, including those that target the microenvironment to inhibit signaling, activate signaling, and specifically involve many new targets such as physical barriers, immune cells and their surface molecular receptors, cytokines, and metabolic factors. Furthermore, it summarizes the challenges faced while conducting research on the tumor immune microenvironment and the corresponding solutions.

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Section: Immunotherapeutic Strategies Targeting the Tmementioning

confidence: 99%

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Bai

Cui

2022

Front. Immunol.

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“…The phase II study MRTX-500 reported that ORR of sitravatinib combined with nivolumab was 16% (11/68) and median OS was 15 months in ICI exposed patients. 21 The phase III studies of ICIs in combination with sitravatinib (NCT03906071) or lenvatinib (NCT03976375) are underway. Other efforts exploring combination strategies for disease progression after ICIs in lung cancer include, but are not limited to, dual immunotherapy involving lymphocyte activation gene-3 (LAG-3) inhibitors, transmembrane immunoglobulin and mucin domain 3 (TIM3) inhibitors, the T cell immunoglobulin and ITIM domain (TIGIT) inhibitors and so on.…”

Section: Discussionmentioning

confidence: 99%

“…Immunotherapy combined with targeted therapy has also shown potential to overcome ICI resistance. The phase II study MRTX‐500 reported that ORR of sitravatinib combined with nivolumab was 16% (11/68) and median OS was 15 months in ICI exposed patients 21 . The phase III studies of ICIs in combination with sitravatinib (NCT03906071) or lenvatinib (NCT03976375) are underway.…”

Section: Discussionmentioning

confidence: 99%

Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy

et al. 2023

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Introduction Immune checkpoint inhibitor (ICI)‐based treatment regimens have become the standard of care for first‐line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild‐type non‐small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first‐line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second‐line therapy options. Plinabulin is a selective immunomodulating microtubule‐binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD‐1) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance. Methods In this investigator‐initiated, single‐arm, open‐label, phase II trial, metastatic NSCLC patients who acquired resistance to first‐line immunotherapy‐based therapy will be enrolled. Participants will receive pembrolizumab 200 mg D1, plinabulin 30 mg/m2 D1 and D8, and docetaxel 75 mg/m2 D1 intravenously for a 21‐day cycle. The study intervention will be given until disease progression, intolerable toxicity, informed consent withdrawal or investigator decision. The primary endpoint is investigator‐based objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary endpoints are progression‐free survival, overall survival, duration of response, and safety. Discussion This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first‐line PD‐1/PD‐L1 inhibitor either as monotherapy or in combination with chemotherapy.

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“…Recently, the LUNG–MAP S1800A phase 2 trial reported that ramucirumab (a CTLA–4/vascular endothelial growth factor [VEGF] inhibitor) plus pembrolizumab achieved improved efficacy (objective response rate [ORR], 28%; median OS, 14.5 months) in patients with NSCLC progressed after anti–PD–(L)1 therapy ( 48 ). Similarly, cabozantinb plus atezolizumab and sitravatinib plus nivolumab, respectively, showed antitumor immune activity for immune–failed patients with NSCLC in the COSMIC–021 and MRTX–500 trials ( 49 , 50 ). Phase 3 trials such as SAPPHIRE are ongoing.…”

Section: Discussionmentioning

confidence: 99%

Global research landscape and trends of lung cancer immunotherapy: A bibliometric analysis

Liu

Han

et al. 2022

Front. Immunol.

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BackgroundImmunotherapy for lung cancer has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer immunotherapy.MethodOn 1 July, 2022, the authors identified 2,941 papers on lung cancer immunotherapy by the Web of Science and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top papers) as well as major journals on lung cancer immunotherapy. After that, recent research hotspots were analyzed based on the latest publications in major journals.ResultsThese 2,941 papers were cited a total of 122,467 times. “Nivolumab vs. docetaxel in advanced non–squamous non–small–cell lung cancer” published in 2015 by Borghaei H et al. was the most cited paper (5,854 citations). Among the journals, New England Journal of Medicine was most influential. Corresponding authors represented China took part in most articles (904) and papers with corresponding authors from the USA were most cited (139.46 citations per paper). Since 2015, anti–PD–(L)1 has become the hottest research area.ConclusionsThis bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on thousands of publications, and further suggests future research directions. Moreover, the results can benefit researchers to select journals and find potential collaborators. This study can help researchers get a comprehensive impression of the research landscape, historical development, and recent hotspots in lung cancer immunotherapy and provide inspiration for further research.

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43P MRTX-500: Phase II trial of sitravatinib (sitra) + nivolumab (nivo) in patients (pts) with non-squamous (NSQ) non-small cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy

Cited by 13 publications

References 0 publications

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Global research landscape and trends of lung cancer immunotherapy: A bibliometric analysis

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