Phase II Study of Platinum (Cisplatin/Carboplatin)and Polymeric Micelles Paclitaxel(Pm-Pac) With Ivonescimab in First Line Metastatic Squamous NSCLC.

NCT07009925 | Not Yet Recruiting Phase 2

• 1 other identifier: MShi
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Squamous Cell Lung Cancer

Keywords

Ivonescimab; Polymeric Micelles paclitaxel; metastatic squamous cell lung cancer; Treatment Outcome; safety

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Objective Response Rate

  Every 6 weeks (RECIST 1.1) until progression (up to 24 months)

• Disease Control Rate

  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

  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

  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

  From first dose until 30 days after the last dose, up to approximately 2 years.

Study Arms (1)

Ivonescimab 20mg/kg combined with polymeric micelles paclitaxel and platinum in squamous NSCLC

EXPERIMENTAL

Drug: Ivonescimab 20mg/kg intravenous every 3 weeks

Interventions

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.

Also known as: paclitaxel polymeric micelles ≤300mg/㎡intravenous every 3 weeks, platinum intravenous every 3 weeks

Ivonescimab 20mg/kg combined with polymeric micelles paclitaxel and platinum in squamous NSCLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be signed before implementing any trial-related procedures;
• Age ≥18 years old;
• Patients with histologically or cytologically confirmed metastatic or recurrent (stage IV) squamous NSCLC (International Association for the Study of Lung Cancer and American Joint Committee on Classification of Cancer, 8th Edition TNM staging), inoperable or inappropriate for radical concurrent chemoradiotherapy, and without previous systemic treatment；. Patients with mixed histology (example adenosquamous) are allowed if there is squamous component in the specimen. PD-L1 immunohistochemical results is required before enrollment.
• According to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), there is at least one measurable lesion.
• 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.
• ECOG score: 0-1 8.Expected survival time \> 3 months 9.Normal organ function, patients should meet the following laboratory indicators:
• Blood routine test should meet the following criteria (no blood transfusion, no use of blood products, granulocyte colony-stimulating factor, or other hematopoietic growth factors within 7 days before blood routine test); White blood cell count ≥3.0x10\^9/L, absolute neutrophil count (ANC) ≥1.5x10\^9/L，Platelet count ≥100×10\^9/L Hemoglobin \>9g/dL. If patients receive blood component transfusion (red blood cells, platelets, etc.) during the screening period, blood routine test should be performed again at an interval of 1 week to meet the above criteria before continuing screening.
• Blood biochemical examination must meet the following criteria: Total bilirubin ≤1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) ≤2.5 times ULN (ALT, AST, or ALP≤ 5×ULN for patients with liver metastases, and ALP≤10×ULN for patients with bone metastases); Serum creatinine ≤1.5 times ULN and creatinine clearance (calculated using Cockcroft-Gault formula) ≥60 ml/min；
• Normal coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
• Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. Subjects with baseline TSH beyond the normal range, but total T3 (or FT3) and FT4 are within the normal range can also be enrolled;
• Myocardial zymogram within the normal range (if the investor judges that the simple laboratory result is not of clinical significance, the patient is allowed to be included); 10.For female patients of childbearing age, a negative urine or serum pregnancy test should be performed within 3 days before the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is requested. Female patients who are not of childbearing age are defined as those who have been postmenopausal for at least 1 year or have undergone surgical sterilization or hysterectomy; 11.If there is a risk of conception, all patients (male or female) are required to use contraception throughout the treatment period until 180 days after the last study drug administration.

You may not qualify if:

• Currently participating in interventional clinical research treatment;
• Has non-squamous histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible; for non-small cell histology if there is any squamous element is present (example adenosquamous), the subject is eligible; the squamous element does not have to be predominant.
• Previously received immunotherapy, including immune checkpoint inhibitors (such as anti-PD-1 /L1 antibodies, anti-CTLA-4 antibodies, anti-LAG-3 antibodies, etc.), immune checkpoint agonists (such as: Subjects of ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immune cell therapy, etc., any treatment targeting the immune mechanism of tumor action;
• known allergic or hypersensitive reactions to any investigational drug or any excipients thereof;
• Tumor invasion of surrounding important organs and blood vessels (such as aorta, heart and pericardium, superior vena cava, trachea, esophagus, etc.) or esophagotracheal fistula or esophagopleural fistula risk;
• Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (subjects who do not require drainage effusion or whose frequency of drainage is less than once per month can be enrolled);
• Patients with symptomatic brain metastases, meningeal metastases, or spinal cord compression;
• There is a history or current presence of non-infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid therapy;
• Serious comorbidities such as a history of severe lung or heart disease, any arterial thrombosis, embolism, or ischemia within 6 months prior to treatment, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack. A history of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolism within the 3 months prior to enrollment (implantable intravenous port or catheter-derived thrombosis, or superficial venous thrombosis was not considered "severe" thromboembolism);
• History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with autoimmune related hypothyroidism receiving stable dose thyroid hormone replacement therapy were eligible to participate in the study. Patients with controlled type 1 diabetes following a stable insulin regimen were eligible to participate in the study.
• Active systemic infections, including tuberculosis (clinical diagnosis including clinical history, physical examination and imaging findings, and TB testing based on local medical practice), hepatitis B (known to be positive for HBV surface antigen (HBsAg), HBV DNA ≥1000cps/ml or the lower limit of its reference value), hepatitis C or human immunodeficiency virus (HIV antibody positive);
• A known mental illness or substance abuse condition that may affect compliance with the test requirements;
• There is a medical history, disease, treatment, or abnormal laboratory result that could interfere with the test results or prevent the subject from fully participating in the study, or the investigator believes that participation in the study is not in the subject's best interest.

Sponsors & Collaborators

• Jiangsu Cancer Institute & Hospital: lead

Related Publications (12)

• 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.

  PMID: 40057343 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.

  PMID: 38820549 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.

  PMID: 34311108 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.

  PMID: 19901853 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.

  PMID: 33433946 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.

  PMID: 33130217 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.

  PMID: 28868573 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.

  PMID: 37593227 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.

  PMID: 39490738 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.

  PMID: 37879536 BACKGROUND

• Frentzas S, Austria Mislang AR, Lemech C, Nagrial A, Underhill C, Wang W, Wang ZM, Li B, Xia Y, Coward JIG. Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 19;12(4):e008037. doi: 10.1136/jitc-2023-008037.

  PMID: 38642937 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.

  PMID: 25601652 BACKGROUND

Central Study Contacts

Qi M Shi

CONTACT

+8613809029766; shimeiqi1963@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: May 30, 2025
• First Posted: June 8, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share