A Randomized, Phase II Study of Anlotinib Combined With Sintilimab(IBI 308) in First-generation EGFR-TKIs Drug Resistance Along With T790M Negative NSCLC
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab
- Conditions
- Carcinoma
- Sponsor
- First Hospital of Shijiazhuang City
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
- Last Updated
- 7 years ago
Overview
Brief Summary
This is an efficacy and safety study of Anlotinib combined with Sintilimab (IBI 308) in participants with advanced or metastatic non-small cell lung cancer (NSCLC) who have received first-generation EGFR-TKIs resistance along with T790M negative.
Detailed Description
Participants receive Sintilimab(IBI 308) 200 mg, administered as intravenous (IV) infusion on Day 1, Anlotinib 12mg, administered as PO on Day1-14 of each 21-day cycle until documented PD.The primary hypothesis of this study is that participants will have a longer Progression Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when treated with Anlotinib plus Sintilimab(IBI 308).
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subjects volunteered to participate in this study and signed the informed consent form, with good compliance and follow-up.
- •Male or female patients aged 18-75 years old.
- •Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV nonsquamous NSCLC.
- •Has confirmation that epidermal growth factor receptor (EGFR) mutation，with first-generation EGFR-TKIs drug resistance T790M negative .
- •Has measurable disease.
- •There is at least one target lesion that has not received radiotherapy in the past 3 months, and it can be accurately measured in at least one direction (the maximum diameter needs to be recorded) by magnetic resonance imaging (MRI) or computed tomography (CT), in which conventional CT is greater than 20mm or spiral CT is greater than 10mm.
- •Has a life expectancy of at least 3 months.
- •Has a performance status of 0 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
- •Has adequate organ function.
- •Patients with asymptomatic or mild brain metastasis may be enrolled.
Exclusion Criteria
- •Squamous cell carcinoma (including adenosquamous carcinoma);Small cell lung cancer (including small cell cancer and non-small cell mixed lung cancer).
- •2.ALK(Anaplastic Lymphoma kinase) positive. 3.Imaging (CT or MRI) showed that the tumor lesion invaded the central tumor of local large blood vessels;Or there is obvious pulmonary cavitation or necrotic tumor.
- •4.History and complications
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.(patients with brain metastasis who have completed treatment 14 days before enrollment and have stable symptoms can be included in the group, but they need to be confirmed as having no symptoms of cerebral hemorrhage by brain MRI, CT).
- •Have Participated in other clinical studies or less than 4 weeks before the end of treatment in the previous clinical study.
- •Other active malignancies requiring concurrent treatment.
- •Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
- •Patients who have not recovered to level 1 or lower of NCI-CTCAE4.0 （The Common Terminology Criteria for Adverse Events 4.0）after previous systemic anti-tumor treatment with anti-tumor treatment-related adverse reactions (except hair loss).
- •Abnormal coagulation function (INR(international normalized ratio) \>1.5 or PT(prothrombin time) \> ULN+4 s or APTT(activated partial thromboplastin time ) \> 1.5ULN), with bleeding tendency or receiving thrombolytic or anticoagulant treatment.
- •Is expected to require any other form of antineoplastic therapy while on study.
Arms & Interventions
Anlotinib Hydrochloride+Sintilimab
Participants receive Sintilimab (IBI 308) 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle , Anlotinib 12mg, administered as PO on Day1-14 of each 21-day cycle until documented PD
Intervention: Sintilimab
Anlotinib Hydrochloride+Sintilimab
Participants receive Sintilimab (IBI 308) 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle , Anlotinib 12mg, administered as PO on Day1-14 of each 21-day cycle until documented PD
Intervention: Anlotinib Hydrochloride
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: 6 months
PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent central radiologists' (BICR) review. Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. (Note: the appearance of one or more new lesions was also considered progression). Participants were evaluated every 9 weeks with radiographic imaging to assess their response to treatment.
Secondary Outcomes
- Over Survival(OS)(2years)
- Objective Response Rate (ORR)(2yeas)