Phase I Study of Osimertinib+Bevacizumab+Carboplatin and Pemetrexed for Untreated Patients With EGFR Mutation Advanced Non-squamous Non-Small Cell Lung Cancer With Concomitant Mutations.
Overview
- Phase
- Phase 2
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- ORR
Overview
Brief Summary
This is a single-center, open-label, phase I clinical trial aimed to evaluate the efficacy and safety of Osimertinib+Bevacizumab+Carboplatin and Pemetrexed for Untreated Patients With EGFR Mutation Advanced Non-squamous Non-Small Cell Lung Cancer With Concomitant Mutations.
Detailed Description
Patients received Bevacizumab, 7.5mg/kg d1, Pemetrexed, 500mg/m2, d1 and Carboplatin AUC5, d1; osimertinib 80mg/d , d1-21, Q3W/cycle; induction therapy for 4 cycle, then Carboplatin was stopped after 4 cycles, and osimertinib combined with bevacizumab and pemetrexed were given for maintenance treatment every 3 weeks; Bevacizumab and pemetrexed were discontinued for 2 years; After that, the maintenance treatment of osimertinib was continued
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects who must meet all the following criteria should be selected:
- •Agree to participate in this trial and sign written informed consent form.
- •Male or female, age between 18 and 70 years.
- •Expected survival time ≥ 3 months and able to be followed-up.
- •Stage IIIB/IIIC/IV non-squamous NSCLC patients without previous systemic therapy (according to AJCC8th) or patients with stage IIIB/IIIC/IV non-squamous NSCLC who have relapsed after surgery (if adjuvant therapy was administered, more than 6 months of drug discontinuation is required).
- •The tumor harbors epidermal growth factor receptor (EGFR) mutations(include 19del, L858R, T790M, G719X, L861Q, S768I, 20 A763-Y764ins), and at least concurrent with TP53
- •Patients can not receive concurrent chemoradiothrapy after multidisciplinary consultation and discussion.
- •At least one measurable tumor indicator along with a lesion with a maximum diameter of ≥ 1 cm (diagnosed by imaging, e.g., CT, MRI, ECT).
- •ECOG PS 0-1 within 7 days before enrollment.
- •Within 14 days prior to the start of treatment, laboratory results of routine blood, liver and kidney function and hormone levels meet the following criteria: white blood cell(WBC) ≥3.5× 109/L, platelets (PLT) ≥ 80 × 109/L, neutrophils (ANC) ≥ 1.5 × 109/L, hemoglobin (HGB) ≥ 80 g/L, aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5 × ULN for liver metastases), alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin (TIBC) ≤ 1.5 × ULN, and alanine aminotransferase (ALT) ≤ 1.5 × ULN. × ULN), alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin (TIBC) ≤ 1.5 × ULN, serum creatinine (CR) ≤ 1.25 × ULN; cortisol and thyroid function are in the normal range.
Exclusion Criteria
- •Subjects who meet any of the following criteria could not participate in this study:
- •non-squamous NSCLC just harbors EGFR mutations
- •Prior treatment with first,second and 3rd EGFR-TKI.
- •Received bevacizumab and/or pemetrexed within 6 months prior to the first dose of study drug.
- •Prior treatment with PD-1/PD-L1 antibodies within 3 months prior to the first dose of study drug.
- •Received anti-tumor monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or major surgical procedure within 1 month prior to the first use of study drug; received chest radiation therapy greater than 30 Gy within 6 months prior to the first use of study drug; received chest radiation therapy at 30 Gy or less within 1 month prior to the first use of study drug.
- •Participating or have participated in investigational drug therapy within 4 weeks prior to the first dose of the trial.
- •Other malignant tumors with disease progression or requiring aggressive treatment within 5 years of enrollment. Exceptions included early-stage tumors (carcinoma in situ or stage I tumors) that received radical treatment, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or carcinoma in situ of the breast that received potentially radical treatment.
- •Having congenital or acquired immune deficiency (e.g., HIV-infected patients), active hepatitis B (HBV-DNA ≥10\^3 copies/ml), or hepatitis C (positive for hepatitis C antibodies and HCV-RNA above the lower limit of detection for the assay).
- •Patients who have received live vaccine within 4 weeks prior to the first administration of study drug are permitted to receive inactivated viral.
Arms & Interventions
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Bevacizumab, 7.5mg/kg, d1; Pemetrexed, 500mg/m2, d1; Carboplatin AUC5, d1; Osimertinib 80mg/d , d1-21; Q3W/cycle induction therapy for 4 cycle. Then Carboplatin was stopped after 4 cycles, and Osimertinib combined with Bevacizumab and Pemetrexed were given for maintenance treatment every 3 weeks for 2 years. After that, the maintenance treatment of Osimertinib was continued.
Intervention: Osimertinib (Drug)
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Bevacizumab, 7.5mg/kg, d1; Pemetrexed, 500mg/m2, d1; Carboplatin AUC5, d1; Osimertinib 80mg/d , d1-21; Q3W/cycle induction therapy for 4 cycle. Then Carboplatin was stopped after 4 cycles, and Osimertinib combined with Bevacizumab and Pemetrexed were given for maintenance treatment every 3 weeks for 2 years. After that, the maintenance treatment of Osimertinib was continued.
Intervention: Bevacizumab Biosimilar IBI305 (Drug)
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Bevacizumab, 7.5mg/kg, d1; Pemetrexed, 500mg/m2, d1; Carboplatin AUC5, d1; Osimertinib 80mg/d , d1-21; Q3W/cycle induction therapy for 4 cycle. Then Carboplatin was stopped after 4 cycles, and Osimertinib combined with Bevacizumab and Pemetrexed were given for maintenance treatment every 3 weeks for 2 years. After that, the maintenance treatment of Osimertinib was continued.
Intervention: Carboplatin (Drug)
Osimertinib+Bevacizumab+Carboplatin and Pemetrexed
Bevacizumab, 7.5mg/kg, d1; Pemetrexed, 500mg/m2, d1; Carboplatin AUC5, d1; Osimertinib 80mg/d , d1-21; Q3W/cycle induction therapy for 4 cycle. Then Carboplatin was stopped after 4 cycles, and Osimertinib combined with Bevacizumab and Pemetrexed were given for maintenance treatment every 3 weeks for 2 years. After that, the maintenance treatment of Osimertinib was continued.
Intervention: Pemetrexed (Drug)
Outcomes
Primary Outcomes
ORR
Time Frame: 2 years
ORR was calculated by the percentage of patients with a confirmed complete (CR) or partial response (PR).
Secondary Outcomes
- PFS(2 years)
- OS(3 years)