Double Guard Efficiency and Safety—Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Simultaneous Blockade of Several Immune Checkpoints—Mechanism of Action
3. Synergistic Role of Anti-PD-1 and Anti-CTLA-4 Antibodies
4. Negative Immune Checkpoints—LAG-3, TIM-3, TIGIT and News
5. Symbiotic Action between Negative and Positive Immune Checkpoints
6. Efficacy of Double Blockade in Immunotherapy-Resistant NSCLC Patients
6.1. Experience with Double Blockade of Immune Checkpoints in ICI-Naïve NSCLC Patients
6.2. Blockade of PD-1 and CTLA-4 Molecules
6.3. Blockade of PD-1/PD-L1 Axis and TIM-3 Molecule
6.4. Blockade of PD-1/PD-L1 Axis and TIGIT Molecule
6.5. Blockade of PD-1/PD-L1 Axis and LAG-3 Molecule
6.6. Other Targets for Double Blockade
6.7. Efficacy and Safety of Agonistic and Antagonistic Antibody Targeted Immune Checkpoints in Immunotherapy-Resistant NSCLC Patients
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Frisone, D.; Friedlaender, A.; Addeo, A.; Tsantoulis, P. The Landscape of Immunotherapy Resistance in NSCLC. Front. Oncol. 2022, 12, 817548. [Google Scholar] [CrossRef] [PubMed]
- Yang, K.; Li, J.; Sun, Z.; Zhao, L.; Bai, C. Retreatment with immune checkpoint inhibitors in solid tumors: A systemic review. Ther. Adv. Med. Oncol. 2020, 12, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Metro, G.; Signorelli, D. Immune checkpoints inhibitors rechallenge in non-small-cell lung cancer: Different scenarios with different solution. Lung Cancer Manag. 2019, 8, LMT18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Catalano, M.; Shabani, S.; Venturini, J.; Ottanelli, C.; Voltolini, L.; Roviello, G. Lung Cancer Immunotherapy: Beyond Common Immune Checkpoints Inhibitors. Cancers 2022, 14, 6145. [Google Scholar] [CrossRef]
- D’arrigo, P.; Tufano, M.; Rea, A.; Vigorito, V.; Novizio, N.; Russo, S.; Romano, M.F.; Romano, S. Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules. Curr. Med. Chem. 2020, 27, 2402–2448. [Google Scholar] [CrossRef]
- Lee, J.B.; Ha, S.-J.; Kim, H.R. Clinical Insights Into Novel Immune Checkpoint Inhibitors. Front. Pharmacol. 2021, 12, 681320. [Google Scholar] [CrossRef]
- Basudan, A.M. The Role of Immune Checkpoint Inhibitors in Cancer Therapy. Clin. Pract. 2022, 13, 22–40. [Google Scholar] [CrossRef]
- Anderson, A.C.; Joller, N.; Kuchroo, V.K. Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity 2016, 44, 989–1004. [Google Scholar] [CrossRef] [Green Version]
- Rotte, A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J. Exp. Clin. Cancer Res. 2019, 38, 255. [Google Scholar] [CrossRef]
- Willsmore, Z.N.; Coumbe, B.G.T.; Crescioli, S.; Reci, S.; Gupta, A.; Harris, R.J.; Chenoweth, A.; Chauhan, J.; Bax, H.J.; McCraw, A.; et al. Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action. Eur. J. Immunol. 2021, 51, 544–556. [Google Scholar] [CrossRef]
- Friedman, C.; Carvajal, R.; Davar, D.; Castanon, E.; Ascierto, P.; Calvo, E.; Hara, M.; Powell, S.; Shapira-Frommer, R.; Garralda, E.; et al. Phase 1/2a study of the novel nonfucosylated anti-CTLA-4 monoclonal antibody BMS-986218 ± nivolumab in advanced solid tumors: Part 1 results. J. Immunother. Cancer 2022, 10 (Suppl. S2), A620. [Google Scholar]
- Triebel, F.; Jitsukawa, S.; Baixeras, E.; Roman-Roman, S.; Genevee, C.; Viegas-Pequignot, E.; Hercend, T. LAG-3, a novel lymphocyte activation gene closely related to CD4. J. Exp. Med. 1990, 171, 1393–1405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kisielow, M.; Kisielow, J.; Capoferri-Sollami, G.; Karjalainen, K. Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cells. Eur. J. Immunol. 2005, 35, 2081–2088. [Google Scholar] [CrossRef]
- Maruhashi, T.; Sugiura, D.; Okazaki, I.-M.; Okazaki, T. LAG-3: From molecular functions to clinical applications. J. Immunother. Cancer 2020, 8, e001014. [Google Scholar] [CrossRef]
- Huard, B.; Mastrangeli, R.; Prigent, P.; Bruniquel, D.; Donini, S.; El-Tayar, N.; Maigret, B.; Dréano, M.; Triebel, F. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc. Natl. Acad. Sci. USA 1997, 94, 5744–5749. [Google Scholar] [CrossRef] [PubMed]
- Workman, C.J.; Dugger, K.J.; Vignali, D.A.A. Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-3. J. Immunol. 2002, 169, 5392–5395. [Google Scholar] [CrossRef] [Green Version]
- Anderson, A.C. Tim-3, a negative regulator of anti-tumor immunity. Curr. Opin. Immunol. 2012, 24, 213–216. [Google Scholar] [CrossRef]
- Huang, Y.-H.; Zhu, C.; Kondo, Y.; Anderson, A.C.; Gandhi, A.; Russell, A.F.; Dougan, S.K.; Petersen, B.-S.; Melum, E.; Pertel, T.; et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 2015, 517, 386–390. [Google Scholar] [CrossRef] [Green Version]
- Saleh, R.; Toor, S.M.; Elkord, E. Targeting TIM-3 in solid tumors: Innovations in the preclinical and translational realm and therapeutic potential. Expert Opin. Ther. Targets 2020, 24, 1251–1262. [Google Scholar] [CrossRef]
- Mercier, I.E.; Lines, J.L.; Noelle, R.J. Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators. Front. Immunol. 2015, 6, 418. [Google Scholar] [CrossRef]
- Dougall, W.C.; Kurtulus, S.; Smyth, M.J.; Anderson, A.C. TIGIT and CD96: New checkpoint receptor targets for cancer immuno-therapy. Immunol. Rev. 2017, 276, 112–120. [Google Scholar] [CrossRef] [PubMed]
- Chauvin, J.-M.; Zarour, H.M. TIGIT in cancer immunotherapy. J. Immunother. Cancer 2020, 8, e000957. [Google Scholar] [CrossRef] [PubMed]
- Manieri, N.A.; Chiang, E.Y.; Grogan, J.L. TIGIT: A Key Inhibitor of the Cancer Immunity Cycle. Trends Immunol. 2017, 38, 20–28. [Google Scholar] [CrossRef] [PubMed]
- Hosseinkhani, N.; Shadbad, M.A.; Asghari Jafarabadi, M.; Karim Ahangar, N.; Asadzadeh, Z.; Mohammadi, S.M.; Lotfinejad, P.; Alizadeh, N.; Brunetti, O.; Fasano, R.; et al. A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers. Int. J. Mol. Sci. 2021, 22, 10389. [Google Scholar] [CrossRef]
- Chen, H.M.; van der Touw, W.; Wang, Y.S.; Kang, K.; Mai, S.; Zhang, J.; Alsina-Beauchamp, D.; Duty, J.A.; Zhang, B.; Mungamuri, A.; et al. Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity. J. Clin. Investig. 2018, 128, 5647–5662. [Google Scholar] [CrossRef] [Green Version]
- Sanmamed, M.F.; Pastor, F.; Rodriguez, A.; Perez-Gracia, J.L.; Rodriguez-Ruiz, M.E.; Jure-Kunkel, M.; Melero, I. Agonists of co-stimulation in cancer im-munotherapy directed against CD137, OX40, GITR, CD27, CD28, and ICOS. Semin. Oncol. 2015, 42, 640–655. [Google Scholar] [CrossRef]
- Solinas, C.; Gu-Trantien, C.; Willard-Gallo, K. The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy. ESMO Open 2020, 5, e000544. [Google Scholar] [CrossRef] [Green Version]
- Peng, C.; Huggins, M.A.; Wanhainen, K.M.; Knutson, T.P.; Lu, H.; Georgiev, H.; Mittelsteadt, K.L.; Jarjour, N.N.; Wang, H.; Hogquist, K.A.; et al. Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells. Immunity 2022, 55, 98–114.e5. [Google Scholar] [CrossRef]
- Paz-Ares, L.G.; Ramalingam, S.S.; Ciuleanu, T.-E.; Lee, J.-S.; Urban, L.; Caro, R.B.; Park, K.; Sakai, H.; Ohe, Y.; Nishio, M.; et al. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes from the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. J. Thorac. Oncol. 2022, 17, 289–308. [Google Scholar] [CrossRef]
- Cho, B.C.; Abreu, D.R.; Hussein, M.; Cobo, M.; Patel, A.J.; Secen, N.; Lee, K.H.; Massuti, B.; Hiret, S.; Yang, J.C.H.; et al. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol. 2022, 23, 781–792. [Google Scholar] [CrossRef]
- Available online: https://clinicaltrials.gov/ct2/show/NCT04294810 (accessed on 10 April 2023).
- Available online: https://clinicaltrials.gov/ct2/show/NCT03262779 (accessed on 10 April 2023).
- Friedman, P.; Ascierto, P.; Davar, D.; O’Hara, M.; Shapira-Frommer, R.; Dallos, M.; Khemka, V.; James, A.; Fischer, B.; Demes, S.; et al. First-in-human phase 1/2a study of the novel nonfu-cosylated anti–CTLA-4 monoclonal antibody BMS-986218 ± nivolumab in advanced solid tumors: Initial phase 1 results. J. Immunother. Cancer 2020, 8 (Suppl. S3), A239. [Google Scholar]
- Engelhardt, J.; Akter, R.; Loffredo, J.; So, P.; Bezman, N.; Price, K. Preclinical characterization of BMS-986218, a novel nonfucosylated anti–CTLA-4 antibody designed to enhance antitumor activity. Cancer Res. 2020, 80 (Suppl. S16), 4552. [Google Scholar] [CrossRef]
- Mach, N.; Curigliano, G.; Santoro, A.; Kim, D.; Tai, D.W.M.; Hodi, S.; Wilgenhof, S.; Doi, T.; Longmire, T.; Sun, H.; et al. Phase (Ph) I/II study of MBG453± spartalizumab (PDR001) in patients (pts) with advanced malignancies. Cancer Res. 2019, 79 (Suppl. S13), CT183. [Google Scholar]
- Harding, J.J.; Moreno, V.; Bang, Y.J.; Hong, M.H.; Patnaik, A.; Trigo, J.; De Miguel, M.J. Blocking TIM-3 in Treatment-refractory Advanced Solid Yumors: A Phase Ia/Ib Study of LY3321367 with or without an Anti-PD-L1 Antibody. Clin. Cancer Res. 2021, 27, 2168–2178. [Google Scholar] [CrossRef]
- Falchook, G.S.; Ribas, A.; Davar, D.; Eroglu, Z.; Wang, J.S.; Luke, J.J.; Hamilton, E.P.; Di Pace, B.; Wang, T.; Ghosh, S.; et al. Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER). J. Clin. Oncol. 2022, 40 (Suppl. S16), 2504. [Google Scholar] [CrossRef]
- Available online: https://clinicaltrials.gov/ct2/show/NCT03708328 (accessed on 10 April 2023).
- Available online: https://clinicaltrials.gov/ct2/show/NCT04958811 (accessed on 10 April 2023).
- Available online: https://clinicaltrials.gov/ct2/show/NCT03977467 (accessed on 10 April 2023).
- Ahn, M.J.; Niu, J.; Kim, D.W.; Rasco, D.; Mileham, K.F.; Chung, H.C.; Vaishampayan, U.N.; Maurice-Dror, C.; Russo, P.L.; Golan, T.; et al. Vibostolimab, an anti-TIGIT antibody, as monotherapy and in combi-nation with pembrolizumab in anti-PD-1/PD-L1-refractory NSCLC. Ann. Oncol. 2020, 31, S887. [Google Scholar] [CrossRef]
- Niu, J.; Maurice-Dror, C.; Lee, D.H.; Kim, D.W.; Nagrial, A.; Voskoboynik, M.; Chung, A.; Mileham, K.; Vaishampayan, U.; Ahn, M.J.; et al. First-in-human phase 1 study of anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer. Ann. Oncol. 2022, 33, 169–180. [Google Scholar] [CrossRef]
- Peters, S.; Lee, D.; Ramlau, R.; Halmos, B.; Schumann, C.; Planchard, D.; Bhagwati, N.; Chen, Q.; Kush, D.; Novello, S. P14.03 Vibostolimab Plus Pembrolizumab with/without Docetaxel vs Docetaxel in NSCLC After Platinum Chemotherapy and Immunotherapy. J. Thorac. Oncol. 2022, 16, S1011–S1012. [Google Scholar] [CrossRef]
- Tawbi, H.A.; Schadendorf, D.; Lipson, E.J.; Ascierto, P.A.; Matamala, L.; Castillo Gutiérrez, E.; Rutkowski, P.; Gogas, H.J.; Lao, C.; Long, G.V. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N. Engl. J. Med. 2022, 386, 24–34. [Google Scholar] [CrossRef]
- Available online: https://clinicaltrials.gov/ct2/show/NCT02750514 (accessed on 10 April 2023).
- Lin, C.-C.; Garralda, E.; Schöffski, P.; Hong, D.; Siu, L.; Martin, M.; Maur, M.; Hui, R.; Soo, R.; Chiu, J.; et al. 387 A Phase II, multicenter study of the safety and efficacy of LAG525 in combination with spartalizumab in patients with advanced malignancies. J. Immunother. Cancer 2020, 8 (Suppl. S3), A235. [Google Scholar]
- Schöffski, P.; Tan, D.S.W.; Martín, M.; Ochoa-De-Olza, M.; Sarantopoulos, J.; Carvajal, R.D.; Kyi, C.; Esaki, T.; Prawira, A.; Akerley, W.; et al. Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies. J. Immunother. Cancer 2022, 10, e003776. [Google Scholar] [CrossRef] [PubMed]
- Johnson, M.; Patel, M.; Ulahannan, S.; Hansen, A.; George, B.; Chu, Q.-C.; Elgadi, M.; Ge, M.; Duffy, C.; Graeser, R.; et al. Phase I study of BI 754111 (anti-LAG-3) plus BI 754091(anti-PD-1) in patients (pts) with advanced solid cancers, followed by expansion in pts with microsatellite stable metastatic colorectal cancer (mCRC), anti-PD-(L)1-pretreated non-small cell lung cancer (NSCLC) and other solid tumors. Ann. Oncol. 2018, 29 (Suppl. S8), viii441. [Google Scholar]
- Johnson, M.L.; Patel, M.R.; Cherry, M.; Kang, Y.-K.; Yamaguchi, K.; Oh, D.-Y.; Hussein, M.A.; Kitano, S.; Kondo, S.; Hansen, A.R.; et al. Safety of BI 75411, an anti-LAG-3 monoclonal antibody (mAb), in combination with BI 754091, an anti-PD-1 mAb, in patients with advanced solid tumors. J. Clin. Oncol. 2020, 38 (Suppl. S15), 3063. [Google Scholar] [CrossRef]
- Available online: https://clinicaltrials.gov/ct2/show/NCT04669899 (accessed on 10 April 2023).
- Shum, E.; Myint, H.; Shaik, J.; Zhou, Q.; Barbu, E.; Morawski, A.; Abukharma, H.; Liu, L.; Nelson, M.; Zeidan, S.; et al. 490 Clinical benefit through Siglec-15 targeting with NC318 antibody in subjects with Siglec-15 positive advanced solid tumors. J. Immunother. Cancer 2021, 9 (Suppl. S2), A520. [Google Scholar] [CrossRef]
- Available online: https://clinicaltrials.gov/ct2/show/NCT04699123 (accessed on 10 April 2023).
- Segal, N.H.; He, A.R.; Doi, T.; Levy, R.; Bhatia, S.; Pishvaian, M.J.; Cesari, R.; Chen, Y.; Davis, C.B.; Huang, B.; et al. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin. Cancer Res. 2018, 24, 1816–1823. [Google Scholar] [CrossRef] [Green Version]
- Hong, D.S.; Gopal, A.K.; Shoushtari, A.N.; Patel, S.P.; He, A.R.; Ramalingam, S.S.; Patnaik, A.; Sandhu, S.; Chen, Y.; Ribas, A.; et al. Utomilumab in patients with immune checkpoint inhibitor-refractory melanoma and non-small-cell lung cancer. Front. Oncol. 2022, 13, 897991. [Google Scholar] [CrossRef] [PubMed]
- Ribas, A.; Chow, L.Q.; Boyd, J.K.; Long, G.V.; Gorczyca, M.; Davis, C.; Pavlov, D.; Thall, A.D. Avelumab (MSB0010718C; anti-PD-L1) in combination with other cancer immunotherapies in patients with advanced malignancies: The phase 1b/2 JAVELIN Medley study. J. Clin. Oncol. 2016, 34 (Suppl. S15), TPS3106. [Google Scholar] [CrossRef]
- Yap, T.A.; Gainor, J.F.; Callahan, M.K.; Falchook, G.S.; Pachynski, R.K. First-in-human phase I/II ICONIC trial of the ICOS agonist voprotelimab alone and with nivolumab: ICOS-high CD4 T-cell populations and predictors of response. Clin. Cancer Res. 2022, 28, 3695–3708. [Google Scholar] [CrossRef]
- Available online: https://clinicaltrials.gov/ct2/show/NCT04549025 (accessed on 10 April 2023).
- Postel-Vinay, S.; Lam, V.K.; Ros, W.; Bauer, T.M.; Hansen, A.R.; Cho, D.C.; Hodi, F.; Schellens, J.H.; Litton, J.K.; Heymach, J.V.; et al. A first-in-human phase I study of the OX40 agonist GSK3174998 (GSK998) +/− pembrolizumab in patients (Pts) with selected advanced solid tumors (ENGAGE-1). Cancer Res. 2020, 80 (Suppl. S16), CT150. [Google Scholar] [CrossRef]
- Chiappori, A.; Thompson, J.; Eskens, F.; Spano, J.-P.; Doi, T.; Hamid, O.; Diab, A.; Rizvi, N.; Hu-Lieskovan, S.; Ros, W.; et al. Results from a combination of OX40 (PF-04518600) and 4–1BB (utomilumab) agonistic antibodies in melanoma and non-small cell lung cancer in a phase 1 dose expansion cohort. J. Immunother. Cancer 2020, 8 (Suppl. S1), A9–A10. [Google Scholar]
Trial Name and Code | Phase | Status | Conditions | No of Patients | Line of Treatment | Interventions | ORR (n,%) | DCR (n,%) | Median DoR (mo) | Median PFS (mo) | Median OS (mo) |
---|---|---|---|---|---|---|---|---|---|---|---|
NCT03262779 | II | Completed | NSCLC | 20 | 1 and ≥2 |
| No results posted | ||||
NCT03110107 | I/IIa | Recruiting | Advanced cancer | 390 | >2 |
| No results posted | ||||
NCT02608268 | I-Ib/II | Terminated (business reason) | Advanced malignancies | 252 | ≥2 |
| 0/17 | 7/17, 46.7% | - | - | - |
NCT03099109 | Ia/Ib | Active, not recruiting | Solid tumors | 275 | ≥2 |
| Cohort C2 (combined therapy) | ||||
0/21 | 14/21, 66.7% | - | 3.7 | - | |||||||
Cohort M1 (monotherapy with LY3321367, no response to prior ICI therapy) | |||||||||||
0/21 | 8/23, 34.8% | - | 1.9 | - | |||||||
Cohort M2 (monotherapy with LY3321367, response to prior ICI therapy) | |||||||||||
1/14, 7.1% | 7/14, 50.0% | - | 7.3 | - | |||||||
NCT02817633 AMBER | I | Recruiting | Advanced solid tumors | 475 | >2 |
| Cobolimab plus nivolumab | ||||
3/7, 42.9% | 3/7, 42.9% | - | - | - | |||||||
Cobolimab plus dostarlimab (including NSCLC, skin cancer, and mesothelioma) | |||||||||||
9/55, 16.4% | 25/50, 50.0% | - | - | - | |||||||
NCT03708328 | I | Active, not recruiting | Advanced solid tumors | 134 | ≥2 |
| No results posted | ||||
NCT04958811 | II | Recruiting | Non-squamous NSCLC | 42 | ≥2 |
| No results posted | ||||
NCT03977467 | II | Recruiting | Advanced solid tumors | 80 | ≥2 |
| No results posted | ||||
NCT02964013 KEYVIBE-001 | I | Active, not recruiting | Advanced solid tumors | 492 | 1 (with CTH) and ≥2 |
| Vibostolimab monotherapy | ||||
1/34, 2.9% | 11/34, 32.4% | 8.5 | 2.0 | - | |||||||
Vibostolimab plus pembrolizumab | |||||||||||
1/33, 3.0% | 13/33, 45.4% | NR | 2.0 | - | |||||||
NCT04725188 KEYVIBE-002 | II | Active, not recruiting | Metastatic NSCLC | 240 | ≥2 |
| No results posted | ||||
NCT02750514 FRACTION-Lung | II | Terminated (changes in SoC) | Advanced NSCLC | 295 | 1 (different therapies) and ≥2 |
| 1/16 (6.25%) patients completed observation before study termination, and 13/16 (81.25%) patients with PD | ||||
NCT02460224 | I/II | Completed | Advanced malignancies | 490 | ≥2 |
| 0/22 | 11/22, 50.0% | 3.5 | - | |
NCT03697304 | II | Active, not recruiting | Advanced solid tumors | 212 | ≥2 |
| No results posted | ||||
NCT03156114 | I | Active, not recruiting | Advanced cancer | 172 | ≥2 |
| No results posted | ||||
NCT03433898 | I | Active, not recruiting | Asian patients with different types of cancer | 146 | ≥2 |
| No results posted | ||||
NCT03780725 | I | Terminated due to company decision | NSCLC, HNSCC | 8 | ≥2 |
| No results posted | ||||
NCT04669899 INNATE | I/II | Recruiting | Advanced refractory solid tumors | 281 | ≥2 |
| No results posted | ||||
NCT03665285 | I/II | Active, not recruiting | SIGLEC-positive advanced solid tumors | 109 | ≥3 |
| 2/13, 15.4% | - | - | - | - |
NCT04699123 | II | Recruiting | Advanced NSCLC | 141 | ≥2 |
| No results posted | ||||
NCT01307267 | I | Completed | Advanced cancer | 190 | ≥2 |
| 0/20 | 10/20, 50.0% | - | 3.6 | - |
NCT02554812JAVELIN Medley | Ib/II | Active, not recruiting | Advanced malignancies | 398 | 1 (different combined therapies) and ≥2 |
| No results posted | ||||
NCT02904226 ICONIC | I/II | Completed | Advanced and/or refractory solid tumors | 242 | 1 (different combined therapies) and ≥2 |
| Vopratelimab monotherapy | ||||
0/7 | 0/7 | - | 1.9 | 3.4 | |||||||
Vopratelimab plus nivolumab | |||||||||||
0/17 | 5/17, 12.5% | - | 1.9 | 12.3 | |||||||
NCT02528357 ENGAGE-1 | I | Completed | Advanced solid tumor | 141 | ≥2 |
| No results posted (regarding ICI-refractory NSCLC patients) | ||||
NCT02315066 | I | Completed | Locally advanced or metastatic cancer | 174 | ≥2 |
| 1/20, 5.0% | 8/20, 40.0% | 5.6 | - | - |
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Kalinka, E.; Wojas-Krawczyk, K.; Krawczyk, P. Double Guard Efficiency and Safety—Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients. Cancers 2023, 15, 3499. https://doi.org/10.3390/cancers15133499
Kalinka E, Wojas-Krawczyk K, Krawczyk P. Double Guard Efficiency and Safety—Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients. Cancers. 2023; 15(13):3499. https://doi.org/10.3390/cancers15133499
Chicago/Turabian StyleKalinka, Ewa, Kamila Wojas-Krawczyk, and Paweł Krawczyk. 2023. "Double Guard Efficiency and Safety—Overcoming Resistance to Immunotherapy by Blocking or Stimulating Several Immune Checkpoints in Non-Small Cell Lung Cancer Patients" Cancers 15, no. 13: 3499. https://doi.org/10.3390/cancers15133499