Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Immunomodulating Agents

patients carry with MET skipping/amplication

immunity therapy

Nong Yang, MD

Yongchang Zhang, MD

In advanced non-small cell lung cancer, there will be some rare mutations, such as ALK, KRAS, etc. The efficacy of these immunotherapies on these different rare mutations has not been reported. Therefore, we conducted this retrospective clinical study to explore the efficacy of immunotherapy for different rare mutations.

A Retrospective Study: Evaluation of the Efficacy of Immunotherapy With Rare Mutations in Non-small Cell Lung Cancer

Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first)

Hunan Province Tumor Hospital

Yongchang Zhang

Director, Head of Medical Oncology, Principal Investigator, Clinical Professor

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Drugs: Toripalimab, 240mg (6ml)/bottle, ivgtt, d1, q3w, administration until PD or death, the longest use time is two years.

Drugs: Bevacizumab, 7.5mg/kg, ivgtt, d1, q3w,the longest use time is two years.

Drugs: Nab-paclitaxel, 260mg/m2,ivgtt,d1 or 130mg/m2,ivgtt,d1,8, q3w, up to six cycles.

Drugs: Carboplatin, AUC=4～5, ivgtt, d1, q3w, up to six cycles.

240mg, ivgtt, d1, every 3 weeks until disease progress or intolerable toxicity, up to 2 years of administration

Toripalimab

7.5mg/kg, ivgtt, d1, every 3 weeks, up to 2 years of administration

260mg/m2,d1 or 130mg/m2,d1,8, ivgtt, every 3 weeks, up to 6 cycles

Nab-paclitaxel

AUC=4～5, d1, ivgtt, every 3 weeks, up to 6 cycles

Juan Li, MD

This study aimed to evaluate the efficacy and safety of first-line Toripalimab combined with bevacizumab, nab-paclitaxel and carboplatin in the treatment of patients with advanced pulmonary sarcomatoid carcinoma.

Pulmonary sarcomatoid carcinoma(PSC) is a rare primary lung cancer, which belongs to the category of non-small cell lung cancer(NSCLC), accounting for about 0.3%-1.3% of lung cancers .Platinum-based combination chemotherapy is the standard adjuvant chemotherapy and palliative chemotherapy for NSCLC, and it is also commonly used for PSC. Advanced PSC has a low response rate to systemic chemotherapy and a short duration of curative effect. The primary progression rate of aggressive platinum-based chemotherapy is 60%-70%, showing that PSC is highly resistant to multiple chemotherapeutics. In recent years, the progress of targeting MET tyrosine kinase mutations has been relatively rapid, but most of the mutant PSCs targeting EGFR, KRAS, ALK, and BRAF V600E are case reports and there is no effective treatments. Immunotherapy has rewritten the treatment pattern of NSCLC. However, the current application of immunotherapy in PSC are mostly case reports. In immunotherapy, IMpower150 research data suggests that the combination of immunity and anti-angiogenesis + platinum-containing dual-agent chemotherapy can bring sustained OS benefits in NSCLC patients , and safety tolerated. However, PSC has moderate to high tumor mutation burden (TMB \>10 mutations/Mb). This high mutation rate may increase tumor immunogenicity, making immunotherapy a better treatment option. At the same time, VEGF, as a cytokine that promotes the growth and differentiation of vascular endothelial cells, plays a decisive role in promoting tumor neovascularization. In this regard, immunotherapy combined with anti-angiogenesis and chemotherapy is worth exploring in the treatment of PSC.

Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma

A Single-arm Exploratory Clinical Study on the Efficacy and Safety of Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma

It is defined as the time interval from randomization of patients to disease progression or death, whichever comes first. There was no progress or the time of disease progression was not recorded when the trial was withdrawn, and the date of the last examination was used as the end date.

The proportion of patients with a best overall confirmed response of CR or PR in the whole body as assessed per RECIST 1.1 by the investigator.

The proportion of patients with a best overall response of CR, PR or SD in the whole body, as assessed per RECIST 1.1 by the investigator.

Defined as the time interval from randomization to death. If the patient continues to survive or his life or death is unknown, the date of death will be reviewed using the latest point in time when the patient is still alive.

AEs per Common Terminology Criteria for Adverse Events (CTCAE V5.0)

Analysis of changes from baseline using the quality of life (QoL) instrument

Sichuan Cancer Hospital and Research Institute

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

All patients received nab-paclitaxel 260 mg/m2, carboplatin AUC=5 and adelbelimumab 1200 mg intravenously on day 1 of each 3-week cycle for 3 cycles. All patients were given conventional drugs to prevent vomiting in each cycle, and intravenous dexamethasone was given to prevent allergy before each dose

All patients received nab-paclitaxel 260 mg/m2 intravenously on day 1 of each 3-week cycle for 3 cycles.

Nab paclitaxel

All patients received carboplatin AUC=5 intravenously on day 1 of each 3-week cycle for 3 cycles.

adelbelimumab

Zhiquan Huang

This study explored the efficacy of adelbelimab (PD-L1 inhibitor) combined with chemotherapy in preoperative induction chemotherapy in patients with locally advanced head and neck squamous cell carcinoma

According to the latest data from the International Agency for Research on Cancer, the new incidence of head and neck cancer in the world in 2022 will be among the top ten new incidences of cancer in the world. In the latest WHO classification of head and neck tumors, head and neck cancers include nasopharyngeal cancer, oral cavity cancer, oropharyngeal cancer, thyroid cancer, laryngeal cancer and other malignant tumors that occur in the head and neck, of which more than 90% are squamous cells cancer. Currently, the standard of care for locally advanced head and neck squamous cell carcinoma (HNSCC) is surgical resection followed by risk-adapted adjuvant radiotherapy, with or without platinum-based chemotherapy, or definitive concurrent chemoradiotherapy. With this aggressive combination therapy, the risk of recurrence, distant metastasis, and death remains high in patients with locally advanced human papillomavirus (HPV)-negative HNSCC. In terms of preoperative induction chemotherapy, clinical studies have shown that patients with tumor remission after preoperative induction chemotherapy have a higher survival rate and a lower risk of distant metastasis, but the postoperative pathological complete remission rate of the tumor is lower , it is difficult to be satisfactory. With the rise of tumor immunology, more and more immunotherapy methods are applied to the clinical treatment of tumors. Current immunotherapies come in many forms, including immune checkpoint inhibitors, co-stimulatory point agonists, antigen vaccines, oncolytic virus therapy, adoptive T cell transfer (ACT) and epidermal growth factor receptor ( Epidermal growth factor receptor, EGFR) targeted therapy. Among them, immune checkpoint inhibitors have been widely used in the clinical treatment of tumors, and the molecular mechanisms of immune checkpoints (immune checkpoint inhibitors, ICIs) are mainly such as programmed cell death 1 (PD-1) and cytotoxic T lymphocytes. Cellular antigen 4 (CTLA-4) is a co-inhibitory receptor expressed on the surface of T cells to negatively regulate T cell-mediated immune responses; however, tumor cells utilize these inhibitory molecules to induce tumor tolerance and T cell exhaustion. Therefore, ICIs such as anti-CTLA-4, anti-PD-1, and anti-PD-L1 can attach to these co-inhibitory receptors to reactivate the immune response against tumor cells. In head and neck squamous cell carcinoma, immune checkpoint inhibitors have been widely used clinically, among which PD-1 inhibitors are the most widely used. A clinical study (KEYNOTE-048) showed that pembrolizumab combined with chemotherapy can significantly improve the survival time of recurrent and metastatic head and neck squamous cell carcinoma. And this is also included in the first-line recommendation of the NCCN guidelines for the treatment of patients with recurrent and metastatic head and neck squamous cell carcinoma. In terms of preoperative neoadjuvant chemotherapy for head and neck squamous cell carcinoma, camrelizumab combined with chemotherapy neoadjuvant chemotherapy in the treatment of locally advanced HNSCC showed high objective response rate and pathological response rate. PD-L1 and PD-L2 are two ligands of PD-1. Both tumor and immune cells can express PD-L1, and PD-L1 is a useful biomarker to predict the response to PD-1/PD-L1 antibodies in patients with different types of cancer. PD-L1 plays a role in inhibiting the cancer-immune cycle by binding to negative regulators of T cell activation such as PD-1 and B7.1. However, PD-L1 inhibitors are currently less used in clinical tumor treatment, mainly focusing on small cell lung cancer. Among them, adelbelimab is a human monoclonal antibody against programmed death ligand 1 (PD-L1), and its safety has been verified to some extent. In a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, the median follow-up time of the test group was 13.5 months and the placebo group was 12.8 months; the hazard ratio was 0.72 \[95% confidence interval 0.58-0.90\]; Compared with one-sided p=0.017), the median overall survival rate of the adelbelimab group was significantly improved (median 15.3 months \[95% CI 13.2-17.5\]) . In terms of head and neck squamous cell carcinoma, only phase I clinical studies have confirmed the safety and tumor activity of PD-L1 inhibitors in treatment. On this basis, this study will further verify the efficacy of preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinoma with PD-L1 inhibitors combined with chemotherapy.

Adelbelimab Combination Chemotherapy in Neoadjuvant Therapy for Squamous Cell Carcinoma of the Head and Neck

A Prospective, Single-arm, Phase II Study of Adelbelimab Combined With Carboplatin and Nab-paclitaxel in Neoadjuvant Therapy for Patients With Resectable Locally Advanced Squamous Cell Carcinoma of the Head and Neck

The postoperative specimens were sent to the pathology department for fixation, sectioning, and observation. Two pathologists judge whether the subject's tumor remains. If there is a disagreement between the two, the third senior pathologist will discuss and decide

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Digestive System Diseases

Rare Diseases

Esophageal Squamous Cell Carcinoma

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Cisplatin

Immunotherapy combined with chemoradiotherapy

1. Sintilimab Body weight \<60kg: 3mg/kg IV Q3W; Body weight ≥60kg: 200mg IV Q3W.
2. Chemotherapy drugs include cisplatin and albumin-bound paclitaxel for injection Paclitaxel for injection (albumin-bound type) dose: 3 dose groups (di=260 mg/m2, di-1=220 mg/m2, di-2=180 mg/m2).

   Dosing on the first day, one cycle every three weeks, a total of 2 cycles. Cisplatin (25mg/m2 IV D1-3 Q3W)
3. Radiotherapy The total dose is 60-66 Gy, divided into 30-33 times (2.0 Gy/f, 5 f per week).

Body weight \<60kg: 3mg/kg IV Q3W; Body weight ≥60kg: 200mg IV Q3W. Every three weeks is a cycle

Sintilimab

Chemotherapy drugs include cisplatin and albumin-bound paclitaxel for injection Paclitaxel for injection (albumin-bound type) dose: 3 dose groups (di=260 mg/m2, di-1=220 mg/m2, di-2=180 mg/m2).

Dosing on the first day, one cycle every three weeks, a total of 2 cycles. Cisplatin (25mg/m2 IV D1-3 Q3W)

Chemotherapy

The total dose is 60-66 Gy, divided into 30-33 times (2.0 Gy/f, 5 f per week).

Radiation Therapy

jiahua lyu, doctor

TAO LI, MD, PhD

Tao Li

This study evaluated the effectiveness and safety of sintilimab combined with cCRT in patients with locally advanced ESCC.

This study evaluated the effectiveness and safety of sintilimab combined with cCRT in patients with locally advanced ESCC. The primary endpoint is PFS. Secondary points contains：ORR、OS、Qol.

Sintilimab Injection Combined With Concurrent CCRT in Locally Advanced Esophageal Squamous Cell Carcinoma

A Prospective, Multi-center, Single-arm Clinical Study of Sintilimab Injection Combined With Concurrent Radiotherapy and Chemotherapy in the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma (IMCORT)

progression-free survival (PFS) refers to the time from enrollment to the first recording of disease progression as determined by RECISTv1.1, or to death due to any cause (whichever occurs first). PFS will be analyzed in the ITT analysis set.

Objective response rate, according to RECISTv1.1, the proportion of patients with CR or PR was determined. If the patient has not undergone a post-baseline assessment, it is considered unremission.

OS refers to the time from enrollment to the first recorded death due to any cause (whichever occurs first).

HRQoL uses EORTCQLQ-C30 to assess the overall health of patients. The post-baseline score of the treatment group was studied, and the score changes from the baseline were summarized descriptively.

HRQoL uses EORTCQLQ-OES18 to assess the overall health of patients. The post-baseline score of the treatment group was studied, and the score changes from the baseline were summarized descriptively.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Retrospective Study: Evaluation of the Efficacy of Immunotherapy With Rare Mutations in Non-small Cell Lung Cancer	NCT04777175	Non Small Cell ...	immunity therap...	18 Years - 75 Years	Hunan Province Tumor Hospital
Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma	NCT04725448	Pulmonary Sarco... Non-small Cell ... Lung Diseases Thoracic Neopla...	Toripalimab Bevacizumab Nab-paclitaxel Carboplatin	18 Years - 75 Years	Sichuan Cancer Hospital and Research Institute
Adelbelimab Combination Chemotherapy in Neoadjuvant Therapy for Squamous Cell Carcinoma of the Head and Neck	NCT06016413	Head and Neck S...	Nab paclitaxel Carboplatin adelbelimumab	18 Years - 75 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Adelbelimab Combination Chemotherapy in Neoadjuvant Therapy for Squamous Cell Carcinoma of the Head and Neck	NCT06016413	Head and Neck S...	Nab paclitaxel Carboplatin adelbelimumab	18 Years - 75 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sintilimab Injection Combined With Concurrent CCRT in Locally Advanced Esophageal Squamous Cell Carcinoma	NCT04602013	Locally Advance...	Sintilimab Chemotherapy Radiation Thera...	18 Years - 75 Years	Sichuan Cancer Hospital and Research Institute

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