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This is a prospective, single-arm, multi-center, phase Ⅱ trial to evaluate the efficacy and safety of Polymeric Micelles paclitaxel(pm-Pac), platinum (cisplatin/carboplatin) in combination with Ivonescimab as first-line treatment in metastatic squamous NSCLC patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ivonescimab 20mg/kg combined with polymeric micelles paclitaxel and platinum in squamous NSCLC | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivonescimab 20mg/kg intravenous every 3 weeks | Drug | Ivonescimab(20mg/kg) combined with paclitaxel polymeric micelles (≤300mg/㎡) and platinum(cisplatin 75mg/㎡or carboplatin AUC5) IV every 3 weeks for 4 cycles.If patient assessment is of clinical benefit, maintenance therapy with ivonescimab or plus polymeric micelles paclitaxel(≤230mg/m^2) can be continued based on investigator's evaluation and patient's own choice until disease progression or unacceptable toxicity. Ivonescimab is administered first, followed by paclitaxel polymeric micelles and platinum.The maximum treatment duration of ivonescimab and polymeric micelles paclitaxel is 24 months. |
| Measure | Description | Time Frame |
|---|---|---|
| progression-free survival | Progression-free Survival (PFS) is defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on RECIST 1.1 assessed by investigator review. | From the start of treatment until disease progression or death (assessed up to 24 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate | Objective Response Rate (ORR) Based on RECIST 1.1 assessed by investigator review, the proportion (%) of patients with confirmed best overall response of complete response (CR) or partial response (PR). | Every 6 weeks (RECIST 1.1) until progression (up to 24 months) |
| Disease Control Rate |
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Inclusion Criteria:
5.According to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), there is at least one measurable lesion.
6.Have not received any previous systemic antitumor therapy for advanced/metastatic diseases. Participants who have previously received platinum-based adjuvant/neoadjuvant chemotherapy, or radical chemoradiotherapy for advanced disease are allowed to enroll if the interval between disease progression or recurrence and the end of the last chemotherapy treatment is at least 6 months.
7.ECOG score: 0-1 8.Expected survival time > 3 months 9.Normal organ function, patients should meet the following laboratory indicators:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qi M Shi | Contact | +8613809029766 | shimeiqi1963@163.com |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40057343 | Background | Xiong A, Wang L, Chen J, Wu L, Liu B, Yao J, Zhong H, Li J, Cheng Y, Sun Y, Ge H, Yao J, Shi Q, Zhou M, Chen B, Han Z, Wang J, Bu Q, Zhao Y, Chen J, Nie L, Li G, Li X, Yu X, Ji Y, Sun D, Ai X, Chu Q, Lin Y, Hao J, Huang D, Zhou C, Shan J, Yang H, Liu X, Wang J, Shang Y, Mei X, Yang J, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhou C. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025 Mar 8;405(10481):839-849. doi: 10.1016/S0140-6736(24)02722-3. | |
| 38820549 |
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IPD will not be available to external researchers due to patient privacy constraints, contractual agreements with sponsors.
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Disease Control Rate (DCR) Based on RECIST 1.1 assessed by investigate review ,the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR), or stable disease (SD). |
| From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first, up to approximately 2 years |
| Duration of Response | Duration of Response (DOR) is defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 assessed by investigator review | From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first, up to approximately 2 years |
| Overall Survival | Overall Survival (OS) was measured from the date of first dose of study drug until date of death from any cause.Participants who were lost to follow-up and the participants who were alive at the date of data cutoff was censored at the date the participant was last known alive, whichever came earlier | From the date of first dose of study drug until date of death from any cause (up to approximately 5 years ) |
| Incidence of Adverse Events | Number of Participants With adverse events (AE), Treatment-releated Adverse Events (TRAEs), Serious Adverse Events (SAEs) and immune-related adverse events (irAE), events will be classified according to CTCAE V5.0. | From first dose until 30 days after the last dose, up to approximately 2 years. |
| Background |
| HARMONi-A Study Investigators; Fang W, Zhao Y, Luo Y, Yang R, Huang Y, He Z, Zhao H, Li M, Li K, Song Q, Du X, Sun Y, Li W, Xu F, Wang Z, Yang K, Fan Y, Liu B, Zhao H, Hu Y, Jia L, Xu S, Yi T, Lv D, Lan H, Li M, Liang W, Wang Y, Yang H, Jia Y, Chen Y, Lu J, Feng J, Liu C, Zhou M, Zhou J, Liu X, Zhou N, He M, Dong X, Chen H, Chen Y, Su H, Li X, Zhang Z, Yang L, Cheng Y, Chen L, Hou X, Zhang Y, Guo J, Wang Z, Lu H, Wu D, Feng W, Li W, Huang J, Wang Y, Song X, Peng J, Liu L, Guo Y, Li W, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhang L. Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA. 2024 Aug 20;332(7):561-570. doi: 10.1001/jama.2024.10613. |
| 34311108 | Background | Socinski MA, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Kong S, Lee A, Coleman S, Zou W, McCleland M, Shankar G, Reck M. IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC. J Thorac Oncol. 2021 Nov;16(11):1909-1924. doi: 10.1016/j.jtho.2021.07.009. Epub 2021 Jul 24. |
| 19901853 | Background | Boyd JA, Hubbs JL, Kim DW, Hollis D, Marks LB, Kelsey CR. Timing of local and distant failure in resected lung cancer: implications for reported rates of local failure. J Thorac Oncol. 2010 Feb;5(2):211-4. doi: 10.1097/JTO.0b013e3181c20080. |
| 33433946 | Background | Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12. |
| 33130217 | Background | Shi M, Gu A, Tu H, Huang C, Wang H, Yu Z, Wang X, Cao L, Shu Y, Wang H, Yang R, Li X, Chang J, Hu Y, Shen P, Hu Y, Guo Z, Tao M, Zhang Y, Liu X, Sun Q, Zhang X, Jiang Z, Zhao J, Chen F, Yu H, Zhang W, Sun J, Li D, Zhou J, Han B, Wu YL. Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial. Ann Oncol. 2021 Jan;32(1):85-96. doi: 10.1016/j.annonc.2020.10.479. Epub 2020 Oct 29. |
| 28868573 | Background | Shi M, Sun J, Zhou J, Yu H, Yu S, Xia G, Wang L, Teng Y, Liu G, Yu C, Feng J, Shen Y. Phase I dose escalation and pharmacokinetic study on the nanoparticle formulation of polymeric micellar paclitaxel for injection in patients with advanced solid malignancies. Invest New Drugs. 2018 Apr;36(2):269-277. doi: 10.1007/s10637-017-0506-4. Epub 2017 Sep 4. |
| 37593227 | Background | Zhao Y, Chen G, Chen J, Zhuang L, Du Y, Yu Q, Zhuang W, Zhao Y, Zhou M, Zhang W, Zhang Y, Wan Y, Li W, Song W, Wang ZM, Li B, Xia M, Yang Y, Fang W, Huang Y, Zhang L. AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial. EClinicalMedicine. 2023 Aug 3;62:102106. doi: 10.1016/j.eclinm.2023.102106. eCollection 2023 Aug. |
| 39490738 | Background | Chen Z, Wu L, Wang Q, Yu Y, Liu X, Ma R, Li T, Li Y, Song X, Li L, Zhao W, Wang Q, Xu X, Lu S. Brief Report: Ivonescimab Combined With Etoposide Plus Carboplatin as First-Line Treatment for Extensive-Stage SCLC: Results of a Phase 1b Clinical Trial. J Thorac Oncol. 2025 Feb;20(2):233-239. doi: 10.1016/j.jtho.2024.10.013. Epub 2024 Oct 28. |
| 37879536 | Background | Wang L, Luo Y, Ren S, Zhang Z, Xiong A, Su C, Zhou J, Yu X, Hu Y, Zhang X, Dong X, Meng S, Wu F, Hou X, Dai Y, Song W, Li B, Wang ZM, Xia Y, Zhou C. A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. J Thorac Oncol. 2024 Mar;19(3):465-475. doi: 10.1016/j.jtho.2023.10.014. Epub 2023 Oct 23. |
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| 25601652 | Background | Voron T, Colussi O, Marcheteau E, Pernot S, Nizard M, Pointet AL, Latreche S, Bergaya S, Benhamouda N, Tanchot C, Stockmann C, Combe P, Berger A, Zinzindohoue F, Yagita H, Tartour E, Taieb J, Terme M. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med. 2015 Feb 9;212(2):139-48. doi: 10.1084/jem.20140559. Epub 2015 Jan 19. |