Sintilimab Combined With Anlotinib in Advanced NSCLC With EGFR Uncommon Mutations

NCT04790409 | Completed Phase 2

• 1 other identifier: IRB-2019-81
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study was a single-arm, open-label, phase II study of PD-1 monoclonal antibody combined with anlotinib in the treatment of advanced non-small cell lung cancer (NSCLC) with EGFR uncommon mutations. Twenty-one patients of NSCLC harboring rare EGFR mutations after previous treatments, including a platinum-based regimen and a targeted treatment (regardless of EGFR Ex20ins), were enrolled. Patients received sintilimab (anti-PD-1) combined with anlotinib (multi-target anti-angiogenesis). The primary endpoint was the objective response rate (ORR) based on RECIST 1.1. Secondary goals included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) based on RECIST 1.1; safety Sex and tolerance. Exploratory objectives include the use of tumor tissue and plasma specimens to detect biomarkers predicting the efficacy of sidilimumab: including but not limited to tumor mutation burden (TMB), PD-L1 expression, etc.; exploring potential predictions in peripheral blood. Biomarkers for anti-group efficacy, including but not limited to TCR.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  objective response rate (ORR)

  objective response rate (ORR) through study completion, an average of 1 year

Study Arms (1)

Sintilimab with anlotinib

EXPERIMENTAL

Patients received sintilimab (anti-PD-1) combined with anlotinib (multi-target anti-angiogenesis).

Drug: sintilimab and anlotinib

Interventions

sintilimab and anlotinib DRUG

This study was a one-arm, open-label, phase II study of PD-1 monoclonal antibody combined with ilotinib in the treatment of advanced EGFR rare-mutant non-small cell lung cancer (NSCLC). 21 patients enrolled in the study who underwent platinum-containing systemic chemotherapy and EGFR-TKI failure were enrolled in the study.

Sintilimab with anlotinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign written informed consent before any trial-related processes are implemented;
• Age ≥ 18 years old and ≤ 75 years old;
• Life expectancy exceeds 3 months;
• The investigator confirmed at least one measurable lesion according to the RECIST 1.1 standard. A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if it is confirmed to have progressed;
• Patients with treated metastatic or recurrent (stage IV) NSCLC confirmed by histology or cytology according to the International Association for the Study of Lung Cancer and the American Association for the Classification of Cancer Classification, 8th edition;
• The Eastern Cancer Cooperative Group (ECOG) has a fitness status score of 0 or 1;
• Patients with genetic testing (allowing PCR and NGS detection methods) confirmed uncommon mutations (EGFR G719X, L861Q, S768I, and 20ins et al.), patients can accept two or more types of EGFR rare co-mutation. Populations with the primary EGFR T790M mutation can also be included in the study.
• Patients who have experienced disease progression after at least two treatment regimens for advanced/metastatic disease must include a platinum-containing systemic chemotherapy and an EGFR-TKI treatment. Patients with EGFR 20ins who have experienced disease progression only after platinum-containing systemic chemotherapy.
• Hematological function is sufficient, defined as absolute neutrophil count ≥1.5×109 /L, platelet count ≥100 ×109 /L, hemoglobin ≥90g/L (no history of blood transfusion within 7 days);
• Hepatic function is adequate, defined as all patients with total bilirubin levels ≤ 1.5 times normal upper limit (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN, or for patients with liver metastases , AST and ALT levels ≤ 5 times ULN;
• adequate renal function, defined as creatinine clearance ≥ 45 ml/min (Cockcroft-Gault formula);
• Coagulation function is adequate, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; if the subject is receiving anticoagulant therapy, as long as the INR or PT is within the range of anticoagulant drugs can;
• Female subjects of childbearing age should be negative for urine or serum pregnancy test within 3 days prior to receiving the first study drug. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required;
• If there is a risk of conception, male and female patients need to use high-efficiency contraception (ie, an annual failure rate of less than 1%) and continue until at least 180 days after stopping the trial treatment; Note: If abstinence is normal for the subject Lifestyle and preferred methods of contraception can be used as a method of contraception.

You may not qualify if:

• Histology is NSCLC, if there are small cell carcinoma, neuroendocrine carcinoma, sarcoma components, it can not be included;
• Patients with known EGFR-sensitive mutations (19-Del and L858R);
• Cavity lung squamous cell carcinoma, or non-small cell lung cancer patients with hemoptysis (\>50 mL/day);
• Patients whose tumor has invaded an important blood vessel or who is judged by the investigator to have major bleeding during the follow-up study;
• Patients with any signs or history of bleeding physique;
• Currently participating in interventional clinical research treatment, or receiving other research drugs or research equipment within 4 weeks prior to the first dose;
• Previously received the following treatments: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or against another stimulus or synergistic inhibition of T cell receptors (eg CTLA-4, OX-40, CD137) drug;
• Received a proprietary Chinese medicine or immunomodulatory drug (thymosin, interferon, interleukin, etc.) with anti-cancer indications within 2 weeks before the first dose, or received major surgery within 3 weeks before the first dose;
• Received a physical organ or blood system transplant;
• There is clinically uncontrollable pleural effusion/peritoneal effusion (patients who do not need drainage or stop drainage and have no significant increase in 3 days of effusion can be enrolled);
• The tumor compresses important organs (such as the esophagus) around it and is accompanied by related symptoms, oppression of the superior vena cava or invasion of the mediastinal vessels, heart, etc.;
• Class III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmias;
• Any arterial thrombosis, embolism or ischemia occurred within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack. A history of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolism within 3 months prior to enrollment (implanted IV port or catheter-derived thrombosis, or superficial vein thrombosis is not considered a "serious" thrombosis embolism);
• It is known that there is an allergic reaction to the active ingredient of sindril mAb and or any excipients;
• Active autoimmune diseases requiring systemic treatment (eg, using disease-modifying drugs, corticosteroids or immunosuppressants) within 2 years prior to the first dose. Alternative therapies (such as thyroxine, insulin, or physiological doses of corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments;

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Related Publications (1)

• Chen K, Xu Y, Huang Z, Yu X, Hong W, Li H, Xu X, Lu H, Xie F, Chen J, Xu Y, Fan Y. Sintilimab plus anlotinib as second- or third-line therapy in metastatic non-small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single-arm, phase II trial. Cancer Med. 2023 Oct;12(19):19460-19470. doi: 10.1002/cam4.6548. Epub 2023 Sep 18.

  PMID: 37723837 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

sintilimab; anlotinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yun Fan

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

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: MD

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: March 10, 2021
• Study Start: August 1, 2019
• Primary Completion: September 13, 2023
• Study Completion: September 13, 2023
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)