Stage 2 enrollment complete: Sitravatinib in combination with nivolumab in NSCLC patients progressing on prior checkpoint inhibitor therapy

Leal, Ticiana; Spira, Alexander I.; Blakely, Collin M.; He, Kai; Berz, David; Richards, Donald A.; Uyeki, James; Savage, A.; Roque, T.; Massarelli, Erminia; Jotte, Robert M.; Chen, I.; Christensen, James G.; Olson, Peter; Tassell, Vanessa; Horn, Leora

doi:10.1093/annonc/mdy288.002

Cited by 11 publications

(4 citation statements)

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“…99 In addition, sitravatinib plus nivolumab combination is under evaluation in a phase III trial in ICI-resistant patients, 100 after a phase II trial showing high tumor regression rate (> 80%) and prolonged treatment duration, despite 17% of treatment discontinuation because of adverse events. 101 Similarly, the combination of pembrolizumab with the anti–vascular endothelial growth factor receptor-2 ramucirumab was well-tolerated and active in patients with NSCLC in a phase I trial 102,103 ; this combination is currently tested within the Lung-MAP master protocol. 104 In the clinical setting, the use of nintedanib in combination with docetaxel represents an option after failure of platinum-doublet chemotherapy.…”

Section: New Strategies To Prevent and Overcome Resistancementioning

confidence: 99%

Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies

Passaro

Brahmer

Antonia

et al. 2022

JCO

152

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A proportion of patients with lung cancer experience long-term clinical benefit with immune checkpoint inhibitors (ICIs). However, most patients develop disease progression during treatment or after treatment discontinuation. Definitions of immune resistance are heterogeneous according to different clinical and biologic features. Primary resistance and acquired resistance, related to tumor-intrinsic and tumor-extrinsic mechanisms, are identified according to previous response patterns and timing of occurrence. The clinical resistance patterns determine differential clinical approaches. To date, several combination therapies are under development to delay or prevent the occurrence of resistance to ICIs, including the blockade of immune coinhibitory signals, the activation of those with costimulatory functions, the modulation of the tumor microenvironment, and the targeting T-cell priming. Tailoring the specific treatments with distinctive biologic resistance mechanisms would be ideal to improve the design and results of clinical trial. In this review, we reviewed the available evidence on immune resistance mechanisms, clinical definitions, and management of resistance to ICIs in lung cancer. We also reviewed data on novel strategies under investigation in this setting.

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Section: New Strategies To Prevent and Overcome Resistancementioning

confidence: 99%

Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies

Passaro

Brahmer

Antonia

et al. 2022

JCO

152

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“…Twenty EGFR-TKI resistant cases and one EGFR-naive case were included. The results show that the median PFS was 5.1 months [88] . In addition, the combination of novel targeted agents with immunotherapy has also shown great prospects.…”

Section: Immunotherapy Combined With Targeted Therapymentioning

confidence: 95%

“…In addition, the combination of novel targeted agents with immunotherapy has also shown great prospects. Nivolumab combined with the small molecule inhibitor sitravatinib in the treatment of patients with advanced non-squamous NSCLC who are resistant to immunotherapy obtained an ORR of 32.14%, a median PFS of 6.8 months, and a median OS of 15.1 months [ 89 ] . Pembrolizumab combined with JAK1 inhibitor itacitinib in the treatment of NSCLC patients with PD-L1 expression > 50% reported an ORR of 66.7%.…”

Section: Immunotherapy-based Combinations To Cope With Resistancementioning

confidence: 99%

Immunotherapy resistance of lung cancer

Yu¹,

Chen²,

Su³

2022

CDR

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In recent years, immunotherapy has made remarkable breakthroughs and brought long-term survival benefits to lung cancer patients. However, a high percentage of patients do not respond to immunotherapy or their responses are transient, indicating the existence of immune resistance. Current studies show that the interactions between cancer cells and immune system are continuous and dynamic. A range of cancer cell-autonomous characteristics, tumor microenvironment factors, and host-related influences account for heterogenous responses. Furthermore, with the identification of new targets of immunotherapy and the development of immune-based combinations, we propose the response strategies to overcome resistance.

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“…Prognostic/predictive biomarkers beyond PD-L1 are needed. 14,15 Several other agents, including monoclonal antibodies (eg, ramucirumab 16 ) and multikinase inhibitors (eg, lenvatinib, 17 sitravatinib 18 ), have been tested in patients with ICIresistant NSCLC. Given encouraging preliminary activity, this led to the development of phase III trials investigating these combinations with ICI in previously treated patients.…”

mentioning

confidence: 99%

Back to the Drawing Board: Overcoming Resistance to PD-1 Blockade

Carlisle,

Liu,

Leal

2024

JCO

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Stage 2 enrollment complete: Sitravatinib in combination with nivolumab in NSCLC patients progressing on prior checkpoint inhibitor therapy

Cited by 11 publications

References 0 publications

Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies

Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies

Immunotherapy resistance of lung cancer

Back to the Drawing Board: Overcoming Resistance to PD-1 Blockade

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