Lung CancerPhase 3NCT06048315
A Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody
A Phase 3 study testing Anlotinib and Penpulimab in people with Lung Cancer and TKI Resistance, run by Degan Lu.
Trial summary
Lung cancer is the second most common malignancy and mortality rate in the world. In the United States and Europe, approximately 10% to 15% of NSCLC patients have epidermal growth factor receptor (EGFR)-sensitive mutations, with higher mutation rates of 30% to 40% in Asia, and objective response rates (ORRs) of 76% to… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Cancer, TKI Resistance, EGFR Sensitive Mutation
- What is being tested?
- Anlotinib and Penpulimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 52 participants
- Where
- No sites listed yet
- Study dates
- Sep 2023to Sep 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Volunteer to participate in clinical research, aged 18-75 years old, regardless of gender, and sign a written informed consent form.
- According to the International Association for the Study of Lung Cancer and the Joint Committee on the American Classification of Cancer, 8th edition TNM staging of lung cancer, locally advanced or metastatic (IIIB, IIIC, IV) NSCLC patients who are confirmed by histology or cytology to be inoperable and unable to undergo radical synchronous radiotherapy and chemotherapy.
- NSCLC patients who have tested positive for EGFR gene sensitive mutations through driver gene testing and have not undergone systematic treatment after EGFR TKI treatment failure.
- Newly treated patients who have not received systemic radiotherapy and chemotherapy in the past, or patients who have relapsed after more than 6 months of follow-up after adjuvant chemotherapy after surgery.
- At least one evaluable lesion judged according to RECIST criteria.
- Men or women aged 18 years ≤ 75 years old.
Show all 13Show fewer
- ECOG PS 0 or 1.
- The expected survival period is ≥ 12 weeks.
- Adequate blood function: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L and platelet count ≥ 90 × 109/L and hemoglobin ≥ 9 g/dL.
- Adequate liver function: Serum bilirubin ≤ 1.5 times the upper limit of normal value (ULN); AST and ALT ≤ 2.5 times the upper limit of normal value (ULN); Alkaline phosphatase ≤ 5 times the upper limit of normal value (ULN).
- Adequate renal function: serum creatinine ≤ upper limit of normal (ULN) or calculated creatinine clearance rate ≥ 60 mL/min.
- Women of childbearing age must have negative pregnancy test results within 28 days prior to enrollment in the study (unless amenorrhea has occurred for 24 months). If the pregnancy test is more than 7 days after the first administration, a urine pregnancy test is required for validation (within 7 days before the first administration).
- If there is a risk of conception, all patients (whether male or female) are required to use contraceptive measures with an annual failure rate of less than 1% throughout the entire treatment period until 120 days after the last study drug administration.
Who cannot join
- Known hypersensitivity to any component contained in the formulation of arotinib or piazepril monoclonal antibody;
- Individuals who are intolerant to the treatment of investigational drugs or are known to be allergic to any investigational drug or its excipients.
- Pregnant or lactating women, or female patients with fertility who have not taken contraceptive measures;
- Existing severe acute infections that have not been controlled; Those who may have purulent or chronic infections, and the wound persists without healing;
- Individuals with previously severe heart disease, including congestive heart failure, uncontrollable high-risk arrhythmia, unstable angina, myocardial infarction, severe heart valve disease, and refractory hypertension;
- Those who suffer from uncontrollable neurological, mental disorders or mental disorders, have poor compliance, and are unable to cooperate and describe treatment responses; Patients with primary brain tumors or central nervous system metastases whose condition has not been controlled and who have obvious intracranial hypertension or neuropsychiatric symptoms;
Show all 19Show fewer
- Have coagulation dysfunction or bleeding tendency, or have a history of thrombotic or hemorrhagic diseases;
- Those undergoing anticoagulation or thrombolysis treatment;
- There are unhealed wounds, ulcers, or fractures;
- Currently participating in interventional clinical research treatment, or receiving other research drugs or using research instruments within 4 weeks before the first administration;
- Has undergone major surgical treatment (excluding surgery for biopsy purposes) within 4 weeks prior to the first study drug administration, or is expected to undergo major surgery during the study period;
- Pulmonary interstitial fibrosis with respiratory failure;
- Patients with chronic obstructive pulmonary disease and respiratory failure;
- Based on chest imaging examination, sputum examination, and clinical examination, it is determined that there is active pulmonary tuberculosis (TB) infection;
- Patients with active, known or suspected autoimmune diseases. Patients with hypothyroidism who only require hormone replacement therapy can be selected;
- Patients who require systemic corticosteroids (with a dose equivalent to>10 mg prednisone/day) or other immunosuppressive drugs within the 14 days prior to enrollment. Patients who use inhaled or topical corticosteroids, as well as patients with adrenal corticosteroid replacement therapy doses equivalent to>10 mg prednisone/day, may participate in the study if there is no active autoimmune disease;
- Previously received PD-1 or PD-L1 antibody treatment for any reason;
- Suffering from other primary malignant tumors before the start of the study;
- Other situations where the researcher believes that patients are not suitable to participate in this trial.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell
Lung cancer is the second most common malignancy and mortality rate in the world. In the United States and Europe, approximately 10% to 15% of NSCLC patients have epidermal growth factor receptor (EGFR)-sensitive mutations, with higher mutation rates of 30% to 40% in Asia, and objective response rates (ORRs) of 76% to 80% with EGFR Tyrosine Kinase Inhibitor (TKI)-targeted therapy. However, resistance mechanisms such as EGFR, MET, PIK3CA and BRAF gene alterations occur with the development of resistance to EGFR-TKI therapy; Median Progression Free Survival (mPFS) for only 2.8-3.2 months; The median overall survival (mOS) is only 7.5-10.6 months. Due to the variety of mechanisms of resistance to EGFR-TKIs and the limited efficacy of chemotherapy, it is necessary to provide salvage treatment for advanced non-small cell lung cancer that is positive for EGFR-sensitive mutations and has failed EGFR TKIs.
Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) used to inhibit tumor angiogenesis and proliferative signaling. The main targets of anlotinib include tyrosine kinase vascular endothelial growth factor receptor 1-3 (VEGFr1-3), fibroblast growth factor receptor 1-4 (Fibroblast Growth Factor Receptor 1-4), platelet-β derived growth factor receptor α and β, and stem cell factor receptor. Anlotinib is rapidly absorbed through the intestine, has high bioavailability, a half-life of 5 days, and is convenient for oral administration, which is conducive to improving patient dependence. IN MAY 2018, THE CHINA FOOD AND DRUG ADMINISTRATION APPROVED ANLOTINIB FOR MARKETING, ENTERED THE MEDICAL INSURANCE CATALOG IN OCTOBER OF THE SAME YEAR, AND WAS RECOMMENDED BY THE CHINESE SOCIETY OF CLINICAL ONCOLOGY (CSCO) FOR THE THIRD-LINE TREATMENT OF LUNG CANCER IN 2019.
Read more
Penpulimab is a humanized immunoglobulin G1 monoclonal antibody (IgG1), which is a class 1 new drug jointly developed by Zhongshan Akeso Biopharmaceutical Co., Ltd. and Chia Tai Tianqing Pharmaceutical Group Co., Ltd., which can specifically bind to PD-1 molecules on the surface of T lymphocytes, thereby blocking the PD-1/PD-L1 pathway that leads to tumor immune tolerance, and reactivating the anti-tumor activity of T lymphocytes to achieve the purpose of treating tumors. A number of preclinical in vitro trials have verified the effect of PEAMPLIMAB in blocking PD-1 pathway, and the results of preclinical pharmacodynamics, animal pharmacokinetics and toxicology have shown that PEAMPLIMAB has good stability, reduced host cell protein residues, and can effectively bind to antigens, and eliminate Fc-mediated effector function, with higher safety.
AK105-201 is a multicenter, double-blind, randomized controlled, phase III clinical trial evaluating the efficacy and safety of pianpulimab combined with carboplatin + paclitaxel in the first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer, the primary endpoint of the study was PFS, and the secondary endpoint was OS, and the results showed that the mPFS group of pianpulimab and the control group were 7.6m and 4.2m, respectively, and the HR was 0.44, reducing the risk of disease progression by 56%. In the 2022 CSCO guidelines for the diagnosis and treatment of non-small cell lung cancer, peamplimab combined with platinum-containing chemotherapy is recommended as the first-line treatment for stage IV driver-free squamous cell carcinoma Grade II. In advanced patients with EGFR TKIs resistance, pemetrexed chemotherapy has a good efficacy, with a median PFS of 2.83 months and a response rate of 22%. The AK105-203 study is a multicenter phase II clinical study led by Professors Jiao Shun and Bai Li of the Chinese PLA General Hospital of the People's Liberation Army of Anlotinib combined with péamplimab in the first-line treatment of hepatocellular carcinoma, with a median follow-up of 23 months and mPFS of 8.8 months.
Therefore, based on the results of the current study on immunosuppressants and antiangiogenic drugs for the treatment of NSCLC, and the current research status in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs, we expect to conduct an exploratory clinical study of PD-1 antibody (péamplimab) combined with anlotinib in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs, with the aim of evaluating the safety of this combination, It was further investigated whether this combination could further improve the survival benefit of patients with advanced NSCLC.
Read the detailed description
Non-small cell lung cancer is the most common type of lung cancer, accounting for 80%-85% of all lung cancers, and about 57% of patients with advanced NSCLC have distant metastases at the time of diagnosis, although chemotherapy, targeted therapy and anti-angiogenic drugs have become the cornerstone of the treatment of advanced NSCLC, but the emergence of immune checkpoint inhibitors in recent years has changed the treatment model of NSCLC. Immune checkpoint inhibitors enhance the body's antitumor activity by inhibiting the immune escape mechanism of tumors, and prolong the survival time of NSCLC patients. According to statistics, the 5-year survival rate of NSCLC patients who join immunotherapy and undergo multi-line therapy can reach 16%.
Previous studies have confirmed that anti-angiogenic drugs and immunotherapy have the effect of improving tumor microenvironment, basic translational and clinical studies have shown that immune checkpoint inhibitors and anti-angiogenic drugs have a synergistic effect, anti-angiogenic drugs can exert immunosuppressive effects by preventing immune invasion of tumors through tissue remodeling and fibrosis, and patients can benefit from PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy.
In the CheckMate 057 and KEYNOTE-001 studies, the ORRs of patients with advanced NSCLC treated with anti-PD-1 monotherapy were 19% (mPFS 2.3 months) and 19.4% (mFS 3.7 months), respectively. The results of Wangpl et al. demonstrated that anti-PD-1 combined with anlotinib in the treatment of advanced NSCLC had an ORR of 28.4%, a DCR of 86.6%, and an mPFS of 6.9 months (95% CI, 5.5-8.3 months), confirming that the combination therapy of anlotinib and anti-PD-1 drugs has a good efficacy and can be used as a second- or third-line treatment in previously treated patients with advanced NSCLC, indicating VEGF-VEGFR2 and PD-1-/ The dual inhibition of the PD-L1 pathway has clinical applicability.
- Conditions
- Lung Cancer, TKI Resistance, EGFR Sensitive Mutation, Anlotinib, Pianzumab
- Being tested
- Anlotinib, Penpulimab
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnlotinibDrug
Also called Frikovi
Every 3 weeks is a treatment cycle, starting from the first day of each treatment cycle with oral administration of 12mg of arotinib once a day, stopping for one week after taking it for two weeks until disease progression (PD), unacceptable toxic reactions, withdrawal of informed consent, end of study, loss of follow-up or death, whichever occurs first.
PenpulimabDrug
Also called Anico
On the first day, Pianzumab (200mg intravenous infusion) was administered every 3 weeks until disease progression (PD), unacceptable toxic reactions, withdrawal of informed consent, end of study, loss of follow-up or death, whichever occurs first.
What is being measured
The primary outcome is the main question the study is designed to answer.
Progress Free Survival
It refers to the time from the patient signing the informed consent form to the earliest occurrence of tumor progression, including death from any cause.
Measured: 12month
Secondary outcomes (3)
Overall Survival
It refers to the time from the patient signing the informed consent form for participating in the study to the time of death due to any reason.
Measured: 12month
Objective Response Rate
Refers to the proportion of patients with partial and complete remission in all patients.
Measured: 12month
Disease Control Rate
The proportion of patients with partial, complete, and stable efficacy among all patients.
Measured: 12month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study startSep 2023 (estimated)
- Primary completionJun 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Degan Lu
- Sponsor type
- University, hospital or other
- Collaborators
- Wu Jieping Medical Foundation
- Responsible party
- Sponsor-investigator, Degan Lu, Qianfoshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06048315
- Sponsor's protocol ID
- YXLL-KY-2023(091)
- Status last verified
- Sep 2023
- First submitted
- 10 Sep 2023
- Last updated
- 21 Sep 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016 Jun;5(3):288-300. doi: 10.21037/tlcr.2016.06.07.
PubMed 27413711Siegel 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.
PubMed 33433946Yang CJ, Hung JY, Tsai MJ, Wu KL, Liu TC, Chou SH, Lee JY, Hsu JS, Huang MS, Chong IW. The salvage therapy in lung adenocarcinoma initially harbored susceptible EGFR mutation and acquired resistance occurred to the first-line gefitinib and second-line cytotoxic chemotherapy. BMC Pharmacol Toxicol. 2017 May 10;18(1):21. doi: 10.1186/s40360-017-0130-0.
PubMed 28486985Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13.
PubMed 29438373Errors in Number at Risk and Author Email Address. JAMA Oncol. 2018 Nov 1;4(11):1625. doi: 10.1001/jamaoncol.2018.5345. No abstract available.
PubMed 30419091Song Y, Zhou K, Jin C, Qian Z, Hou M, Fan L, Li F, Ding K, Zhou H, Li X, Chen B, Sun X, Song X, Jiang M, Zhang Q, Liu L, Yu G, Hu Y, Zhao Z, Liu L, Xue H, Luo J, He B, Jin X, Zhao M, Li B, Xia Y, Zhu J. Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201). Front Oncol. 2022 Jul 7;12:925236. doi: 10.3389/fonc.2022.925236. eCollection 2022.
PubMed 35875118Wang P, Fang X, Yin T, Tian H, Yu J, Teng F. Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non-Small-Cell Lung Cancer After Previous Systemic Treatment Failure-A Retrospective Study. Front Oncol. 2021 Mar 15;11:628124. doi: 10.3389/fonc.2021.628124. eCollection 2021.
PubMed 33791214Han C, Ye S, Hu C, Shen L, Qin Q, Bai Y, Yang S, Bai C, Zang A, Jiao S, Bai L. Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203). Front Oncol. 2021 Jul 13;11:684867. doi: 10.3389/fonc.2021.684867. eCollection 2021.
PubMed 34327136
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell
- ClinicalTrials.gov ID
- NCT06048315
- Acronym / sponsor ID
- YXLL-KY-2023(091)
- Conditions
- Lung Cancer, TKI Resistance, EGFR Sensitive Mutation, Anlotinib, Pianzumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Degan LuUniversity, hospital or other
- Collaborators
- Wu Jieping Medical Foundation
- Study start
- Sep 2023 (estimated)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 21 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Lung cancer is the second most common malignancy and mortality rate in the world. In the United States and Europe, approximately 10% to 15% of NSCLC patients have epidermal growth factor receptor (EGFR)-sensitive mutations, with higher mutation rates of 30% to 40% in Asia, and objective response rates (ORRs) of 76% to 80% with EGFR Tyrosine Kinase Inhibitor (TKI)-targeted therapy. However, resistance mechanisms such as EGFR, MET, PIK3CA and BRAF gene alterations occur with the development of resistance to EGFR-TKI therapy; Median Progression Free Survival (mPFS) for only 2.8-3.2 months; The median overall survival (mOS) is only 7.5-10.6 months. Due to the variety of mechanisms of resistance to EGFR-TKIs and the limited efficacy of chemotherapy, it is necessary to provide salvage treatment for advanced non-small cell lung cancer that is positive for EGFR-sensitive mutations and has failed EGFR TKIs.
Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) used to inhibit tumor angiogenesis and proliferative signaling. The main targets of anlotinib include tyrosine kinase vascular endothelial growth factor receptor 1-3 (VEGFr1-3), fibroblast growth factor receptor 1-4 (Fibroblast Growth Factor Receptor 1-4), platelet-β derived growth factor receptor α and β, and stem cell factor receptor. Anlotinib is rapidly absorbed through the intestine, has high bioavailability, a half-life of 5 days, and is convenient for oral administration, which is conducive to improving patient dependence. IN MAY 2018, THE CHINA FOOD AND DRUG ADMINISTRATION APPROVED ANLOTINIB FOR MARKETING, ENTERED THE MEDICAL INSURANCE CATALOG IN OCTOBER OF THE SAME YEAR, AND WAS RECOMMENDED BY THE CHINESE SOCIETY OF CLINICAL ONCOLOGY (CSCO) FOR THE THIRD-LINE TREATMENT OF LUNG CANCER IN 2019.
Penpulimab is a humanized immunoglobulin G1 monoclonal antibody (IgG1), which is a class 1 new drug jointly developed by Zhongshan Akeso Biopharmaceutical Co., Ltd. and Chia Tai Tianqing Pharmaceutical Group Co., Ltd., which can specifically bind to PD-1 molecules on the surface of T lymphocytes, thereby blocking the PD-1/PD-L1 pathway that leads to tumor immune tolerance, and reactivating the anti-tumor activity of T lymphocytes to achieve the purpose of treating tumors. A number of preclinical in vitro trials have verified the effect of PEAMPLIMAB in blocking PD-1 pathway, and the results of preclinical pharmacodynamics, animal pharmacokinetics and toxicology have shown that PEAMPLIMAB has good stability, reduced host cell protein residues, and can effectively bind to antigens, and eliminate Fc-mediated effector function, with higher safety.
AK105-201 is a multicenter, double-blind, randomized controlled, phase III clinical trial evaluating the efficacy and safety of pianpulimab combined with carboplatin + paclitaxel in the first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer, the primary endpoint of the study was PFS, and the secondary endpoint was OS, and the results showed that the mPFS group of pianpulimab and the control group were 7.6m and 4.2m, respectively, and the HR was 0.44, reducing the risk of disease progression by 56%. In the 2022 CSCO guidelines for the diagnosis and treatment of non-small cell lung cancer, peamplimab combined with platinum-containing chemotherapy is recommended as the first-line treatment for stage IV driver-free squamous cell carcinoma Grade II. In advanced patients with EGFR TKIs resistance, pemetrexed chemotherapy has a good efficacy, with a median PFS of 2.83 months and a response rate of 22%. The AK105-203 study is a multicenter phase II clinical study led by Professors Jiao Shun and Bai Li of the Chinese PLA General Hospital of the People's Liberation Army of Anlotinib combined with péamplimab in the first-line treatment of hepatocellular carcinoma, with a median follow-up of 23 months and mPFS of 8.8 months.
Therefore, based on the results of the current study on immunosuppressants and antiangiogenic drugs for the treatment of NSCLC, and the current research status in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs, we expect to conduct an exploratory clinical study of PD-1 antibody (péamplimab) combined with anlotinib in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs, with the aim of evaluating the safety of this combination, It was further investigated whether this combination could further improve the survival benefit of patients with advanced NSCLC.
Detailed description
Non-small cell lung cancer is the most common type of lung cancer, accounting for 80%-85% of all lung cancers, and about 57% of patients with advanced NSCLC have distant metastases at the time of diagnosis, although chemotherapy, targeted therapy and anti-angiogenic drugs have become the cornerstone of the treatment of advanced NSCLC, but the emergence of immune checkpoint inhibitors in recent years has changed the treatment model of NSCLC. Immune checkpoint inhibitors enhance the body's antitumor activity by inhibiting the immune escape mechanism of tumors, and prolong the survival time of NSCLC patients. According to statistics, the 5-year survival rate of NSCLC patients who join immunotherapy and undergo multi-line therapy can reach 16%.
Previous studies have confirmed that anti-angiogenic drugs and immunotherapy have the effect of improving tumor microenvironment, basic translational and clinical studies have shown that immune checkpoint inhibitors and anti-angiogenic drugs have a synergistic effect, anti-angiogenic drugs can exert immunosuppressive effects by preventing immune invasion of tumors through tissue remodeling and fibrosis, and patients can benefit from PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy.
In the CheckMate 057 and KEYNOTE-001 studies, the ORRs of patients with advanced NSCLC treated with anti-PD-1 monotherapy were 19% (mPFS 2.3 months) and 19.4% (mFS 3.7 months), respectively. The results of Wangpl et al. demonstrated that anti-PD-1 combined with anlotinib in the treatment of advanced NSCLC had an ORR of 28.4%, a DCR of 86.6%, and an mPFS of 6.9 months (95% CI, 5.5-8.3 months), confirming that the combination therapy of anlotinib and anti-PD-1 drugs has a good efficacy and can be used as a second- or third-line treatment in previously treated patients with advanced NSCLC, indicating VEGF-VEGFR2 and PD-1-/ The dual inhibition of the PD-L1 pathway has clinical applicability.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Volunteer to participate in clinical research, aged 18-75 years old, regardless of gender, and sign a written informed consent form.
- According to the International Association for the Study of Lung Cancer and the Joint Committee on the American Classification of Cancer, 8th edition TNM staging of lung cancer, locally advanced or metastatic (IIIB, IIIC, IV) NSCLC patients who are confirmed by histology or cytology to be inoperable and unable to undergo radical synchronous radiotherapy and chemotherapy.
- NSCLC patients who have tested positive for EGFR gene sensitive mutations through driver gene testing and have not undergone systematic treatment after EGFR TKI treatment failure.
- Newly treated patients who have not received systemic radiotherapy and chemotherapy in the past, or patients who have relapsed after more than 6 months of follow-up after adjuvant chemotherapy after surgery.
- At least one evaluable lesion judged according to RECIST criteria.
Key exclusion criteria (19 listed)
- Known hypersensitivity to any component contained in the formulation of arotinib or piazepril monoclonal antibody;
- Individuals who are intolerant to the treatment of investigational drugs or are known to be allergic to any investigational drug or its excipients.
- Pregnant or lactating women, or female patients with fertility who have not taken contraceptive measures;
- Existing severe acute infections that have not been controlled; Those who may have purulent or chronic infections, and the wound persists without healing;
- Individuals with previously severe heart disease, including congestive heart failure, uncontrollable high-risk arrhythmia, unstable angina, myocardial infarction, severe heart valve disease, and refractory hypertension;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnlotinibAlso: FrikoviEvery 3 weeks is a treatment cycle, starting from the first day of each treatment cycle with oral administration of 12mg of arotinib once a day, stopping for one week after taking it for two weeks until disease progression (PD), unacceptable toxic reactions, withdrawal of informed consent, end of study, loss of follow-up or death, whichever occurs first. | Drug | – |
| PenpulimabAlso: AnicoOn the first day, Pianzumab (200mg intravenous infusion) was administered every 3 weeks until disease progression (PD), unacceptable toxic reactions, withdrawal of informed consent, end of study, loss of follow-up or death, whichever occurs first. | Drug | – |
Primary outcome
Progress Free Survival
Time frame: 12month
It refers to the time from the patient signing the informed consent form to the earliest occurrence of tumor progression, including death from any cause.
3 secondary outcomes
Overall Survival
Time frame: 12month
Objective Response Rate
Time frame: 12month
Disease Control Rate
Time frame: 12month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Results publication: PubMed 27413711Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016 Jun;5(3):288-300. doi: 10.21037/tlcr.2016.06.07.
- Results publication: PubMed 33433946Siegel 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.
- Results publication: PubMed 28486985Yang CJ, Hung JY, Tsai MJ, Wu KL, Liu TC, Chou SH, Lee JY, Hsu JS, Huang MS, Chong IW. The salvage therapy in lung adenocarcinoma initially harbored susceptible EGFR mutation and acquired resistance occurred to the first-line gefitinib and second-line cytotoxic chemotherapy. BMC Pharmacol Toxicol. 2017 May 10;18(1):21. doi: 10.1186/s40360-017-0130-0.
- Results publication: PubMed 29438373Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13.
- Results publication: PubMed 30419091Errors in Number at Risk and Author Email Address. JAMA Oncol. 2018 Nov 1;4(11):1625. doi: 10.1001/jamaoncol.2018.5345. No abstract available.
- Results publication: PubMed 35875118Song Y, Zhou K, Jin C, Qian Z, Hou M, Fan L, Li F, Ding K, Zhou H, Li X, Chen B, Sun X, Song X, Jiang M, Zhang Q, Liu L, Yu G, Hu Y, Zhao Z, Liu L, Xue H, Luo J, He B, Jin X, Zhao M, Li B, Xia Y, Zhu J. Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201). Front Oncol. 2022 Jul 7;12:925236. doi: 10.3389/fonc.2022.925236. eCollection 2022.
- Results publication: PubMed 33791214Wang P, Fang X, Yin T, Tian H, Yu J, Teng F. Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non-Small-Cell Lung Cancer After Previous Systemic Treatment Failure-A Retrospective Study. Front Oncol. 2021 Mar 15;11:628124. doi: 10.3389/fonc.2021.628124. eCollection 2021.
- Results publication: PubMed 34327136Han C, Ye S, Hu C, Shen L, Qin Q, Bai Y, Yang S, Bai C, Zang A, Jiao S, Bai L. Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203). Front Oncol. 2021 Jul 13;11:684867. doi: 10.3389/fonc.2021.684867. eCollection 2021.
- Individual participant dataSharing planned: Yes
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Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anlotinib and Penpulimab in people with Lung Cancer and TKI Resistance, run by Degan Lu.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lu DeGan (18753157623, deganlu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progress Free Survival (time frame: 12month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06048315, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.