Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Immune System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Hypersensitivity

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Befotertinib (75 mg or 100 mg orally, once daily) and Icotinib placebo(125 mg orally, three times daily)，in accordance with the randomization schedule

Icotinib (125 mg orally, three times daily) and Befotertinib placebo (75 mg or 100 mg orally, once daily)，in accordance with the randomization schedule

The initial dose of Befotertinib is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days.

Befotertinib can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis)

Icotinib placebo 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis).

Befotertinib + Icotinib placebo

Icotinib 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis).

The initial dose of Befotertinib placebo is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days.

Befotertinib placebo can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis.

Icotinib + Befotertinib placebo

Shun Lu, M.D.

This multicenter, randomized, controlled, double-blind, double-simulated, Phase III study is designed to evaluate the efficacy and safety of Befotertinib compared with Icotinib as adjuvant treatment in EGFR-sensitive mutation-positive stage IB-IIIB (T3N2M0) non-small cell lung cancer after surgical resection.

Adjuvant Befotertinib in Stage IB-IIIB Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations

A Multicenter, Randomized, Controlled, Double Blind, Double Simulated, Phase III Clinical Study of Befotertinib vs Icotinib for Postoperative Adjuvant Treatment of IB-IIIB (T3N2M0) Stage Non Small Cell Lung Cancer With Positive EGFR Sensitive Mutations

Betta Pharmaceuticals Co., Ltd.

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Osimertinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants receive BL-B01D1 in combination with Osimertinib Mesylate Tablets in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.

BL-B01D1

Osimertinib Mesylate Tablets will be administered at a fixed dose of 80mg daily.

Osimertinib Mesylate Tablets

Hai Zhu, PHD

Sa Xiao, PHD

Tao Gui

Caicun Zhou, PHD

A Phase II clinical study to evaluate the efficacy and safety of BL-B01D1 for injection in combination with Osimertinib Mesylate Tablets in patients with locally advanced or metastatic non-small cell lung cancer with EGFR-sensitive mutations

Objective: To evaluate the safety, tolerability, and efficacy of BL-B01D1 in combination with Osimertinib Mesylate Tablets in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, and to further explore the optimal dose and mode of combination. Secondary objective: To evaluate the PK, immunogenicity, and drug-drug interaction (DDI) of the investigational drug BL-B01D1. Exploratory objective: To explore potential predictive, prognostic biomarkers in relation to study drug therapy responses, including levels of biomarkers, including but not limited to EGFR, HER3, etc., in archived and/or fresh tumor tissue and blood samples obtained before and/or after study therapy completion, and/or at the time of disease progression.

A Study of BL-B01D1 Combined With Osimertinib Mesylate Tablets in Patients With Non-small Cell Lung Cancer

A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-B01D1 for Injection in Combination With Osimertinib Mesylate Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With EGFR-sensitive Mutations

The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-B01D1.

ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.

The PFS is defined as the time from the participant's first dose of BL-B01D1 to the first date of either disease progression or death, whichever occurs first.

The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]).

The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.

TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B01D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1.

Sichuan Baili Pharmaceutical Co., Ltd.

Paclitaxel

Albumin-Bound Paclitaxel

Antibodies

Antibodies, Monoclonal

Tin Fluorides

Immunoglobulins

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.

Anlotinib

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.

Penpulimab

Lu DeGan

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.

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.

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 Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell

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.

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.

Refers to the proportion of patients with partial and complete remission in all patients.

The proportion of patients with partial, complete, and stable efficacy among all patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Adjuvant Befotertinib in Stage IB-IIIB Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations	NCT06041776	Non-Small Cell ... EGFR Sensitive ... Adjuvant Therap...	Befotertinib + ... Icotinib + Befo...	18 Years -	Betta Pharmaceuticals Co., Ltd.
A Study of BL-B01D1 Combined With Osimertinib Mesylate Tablets in Patients With Non-small Cell Lung Cancer	NCT05880706	Non-small Cell ...	BL-B01D1 Osimertinib Mes...	18 Years -	Sichuan Baili Pharmaceutical Co., Ltd.
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	NCT06048315	Lung Cancer TKI Resistance EGFR Sensitive ... Anlotinib Pianzumab	Anlotinib Penpulimab	18 Years - 75 Years	Qianfoshan Hospital
A Study of BL-B01D1 Combined With Osimertinib Mesylate Tablets in Patients With Non-small Cell Lung Cancer	NCT05880706	Non-small Cell ...	BL-B01D1 Osimertinib Mes...	18 Years -	Sichuan Baili Pharmaceutical Co., Ltd.

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