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Lung CancerPhase 2NCT04790409

Sintilimab Combined With Anlotinib in Advanced NSCLC With EGFR Uncommon Mutations

A Phase 2 study testing sintilimab and anlotinib in people with Lung Cancer, run by Zhejiang Cancer Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lung Cancer
What is being tested?
sintilimab and anlotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteChina
Study dates
1 Aug 2019to 13 Sep 2023
Phase
Phase 2
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

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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;
  • Patients who require long-term systemic use of corticosteroids. Patients with intermittent use of bronchodilators, inhaled corticosteroids, or topical corticosteroids due to COPD or asthma may be enrolled.
  • has not fully recovered from toxicity and/or complications caused by any intervention prior to initiation of treatment (ie, ≤1 or baseline, excluding fatigue or alopecia);
  • diagnosis within 5 years prior to initial dosing For other malignancies, it does not include radical cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radically resected carcinoma in situ. If more than 5 years before the drug is diagnosed as other malignant tumors or lung cancer, pathological or cytological diagnosis of recurrent metastatic lesions is required;
  • symptomatic central nervous system metastasis. For patients with asymptomatic brain metastases or brain metastases with stable symptoms after treatment, as long as all the following criteria are met, participate in this study: measurable lesions outside the central nervous system; no midbrain, pons, cerebellum, meninges, Medulla or spinal cord metastasis; maintain clinical stability for at least 2 weeks; stop hormone therapy 14 days before the first study drug;
  • One year before the first dose, a history of non-infectious pneumonia requiring corticosteroid treatment or the presence of non-infectious pneumonia;
  • active infections requiring treatment or systemic anti-infectives used within one week prior to first administration;
  • There are known cases of mental illness or substance abuse that may have an impact on compliance with the test requirements;
  • A history of human immunodeficiency virus (HIV) infection (ie, HIV 1/2 antibody positive), known syphilis infection (positive syphilis antibody), and active tuberculosis are known.
  • Untreated active hepatitis B; Note: Hepatitis B subjects meeting the following criteria are also eligible for inclusion:
  • The HBV viral load must be <1000 copies/ml (200 IU/ml) or below the lower limit of detection before the first dose. Subjects should receive anti-HBV treatment during the entire study chemotherapy drug treatment to avoid viral reactivation. For subjects with anti-HBc(+), HBsAg(-), anti-HBs(-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but viral reactivation is closely monitored;
  • Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection);
  • Vaccination with live vaccine within 30 days prior to first dose; Note: Injectable inactivated virus vaccine for seasonal influenza is permitted; however, live attenuated influenza vaccine for intranasal administration is not permitted;
  • There are medical history, disease, treatment, or laboratory abnormalities that may interfere with the test results, hinder the subject's full participation in the study, or the investigator believes that participating in the study is not in the best interest of the subject.
  • Local or systemic diseases caused by non-malignant tumors, or secondary reactions to cancer, and may lead to higher medical risks and/or uncertainty in survival assessment.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310022

Other trials in China

About this study

Official title: Department of Medical Oncology, Zhejiang Cancer Hospital

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.

Read the detailed description

This clinical trial (NCT04790409) entitled " Sintilimab Combined with Anlotinib in Advanced NSCLC with EGFR Uncommon Mutations" has been approved by the Ethics Committee of Zhejiang Cancer Hospital in June 12, 2019 (IRB-2019-81). Meanwhile, we registered our project information on the ClinicalTrials.gov PRS in June, 2019 and obtained the status of "approved". In this study, the first patient received treatment on August 26, 2019. However, due to inexperience and misunderstanding, we wrongly missed the next stage of "released" in PRS. Until we realize our mistakes, the initial release time can only be on 02/18/2021. Therefore, we amend the initial release time here.

Conditions
Lung Cancer
Being tested
sintilimab and anlotinib
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sintilimab and anlotinibDrug

    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.

Study groups in NCT04790409
Study groupRoleWhat they receive
Sintilimab with anlotinibExperimentalPatients received sintilimab (anti-PD-1) combined with anlotinib (multi-target anti-angiogenesis).
Receives: Drug: sintilimab and anlotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. objective response rate (ORR)

    objective response rate (ORR)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2021
  2. Study start1 Aug 2019
  3. Primary completion13 Sep 2023
  4. Study completion13 Sep 2023

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04790409
Sponsor's protocol ID
IRB-2019-81
Status last verified
Sep 2023
First submitted
18 Feb 2021
Last updated
14 Sep 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37723837

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sintilimab and anlotinib in people with Lung Cancer, run by Zhejiang Cancer Hospital at 1 site in China.

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 14 inclusion and 29 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: finished, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

objective response rate (ORR) (time frame: objective response rate (ORR) through study completion, an average of 1 year). 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 NCT04790409, which also lists 1 linked publication.

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 14 Sep 2023.

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