Neoadjuvant Immunotherapy in EGFR-mutant Localized NSCLC

Non-small Cell Lung Cancer Clinical Trial

— NEOTIDE  

Official title:

Neoadjuvant Sintilimab Plus Chemotherapy in EGFR-mutant Stage II-IIIB NSCLC: A Single-arm, Open-label Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05244213
• Other study ID #: CTONG2104
• Status: Recruiting
• Phase: Phase 2
• Start date: June 4, 2022
• Est. completion date: December 1, 2025

Study information

• Verified date: March 2023
• Source: Guangdong Provincial People's Hospital
• Contact: Wen-zhao Zhong, PhD
• Phone: +86 20 83827812
• Email: syzhongwenzhao[@]scut.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Sintilimab plus chemotherapy in EGFR-mutant stage IIB-IIIB NSCLC (excluding N3) followed by optional adjuvant treatment upon investigators' decisions.

Description:

35 eligible patients will be enrolled and 3 cycles of Sintilimab 200mg + doublet platinum-based chemotherapy will be administered. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients who showed inferior response to neoadjuvant treatment leading to unresectable disease will be scheduled for local radiation or other potential subsequent treatment regarding multidisciplinary discussion. After completion of local treatment (surgery or radiation), patients will be provided with optional adjuvant treatment including EGFR-TKI upon investigators' consideration. Patients will be followed with 5 years after surgery. The primary objective of the study is major pathological response (MPR) defined as no more than 10% residual tumor found in primary lung cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 1, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age :18 Years to 75 Years;

2. ECOG physical score 0-1 points; expected survival time = 3 months;

3. Pathologically confirmed diagnosis with Stage II-IIIB(N2) NSCLC which harbored sensitive and rare EGFR alteration. Suspected N2 disease should be confirmed by either mediastinoscopy or EBUS. N1 disease could be determined through PET/CT but biopsy of primary lung cancer is needed;

4. At least one measurable target lesion according to the RECIST 1.1 standard;

5. The main organ function meets the following criteria: 1) blood routine: absolute value of neutrophils = 1.5 × 109 / L, platelets = 75 × 109 / L, hemoglobin = 80 g / L; 2) blood biochemistry: total bilirubin = 1.5 times the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase = 2.5 times the upper limit of normal value (if liver metastasis, = upper limit of normal value 5 times), serum creatinine = 1.5 times the upper limit of normal;

6. Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.

Exclusion Criteria:

1. Stage I and stage IV NSCLC;

2. Large panel NGS indicated ALK fusion or any other driver mutations;

3. Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);

4. Patients who have previously used any other anti-tumor drugs or radiotherapy;

5. A history of active bleeding within the 6 months before enrollment, or receiving thrombolysis or anticoagulant therapy, or the investigator believes that there is a clear tendency to gastrointestinal bleeding (such as esophageal varices with bleeding risk, local activity) Ulcer lesions, etc.) or active hemoptysis;

6. Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections;

7. Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;

8. Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;

9. Patients with low compliance or willingness to take the drugs and surveillance.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• EGFR Activating Mutation
• Non-small Cell Lung Cancer

Intervention

Biological:
• Sintilimab
200mg Q3W

Drug:
• Carboplatin
AUC 5, d1 every 3 weeks
• Nab paclitaxel
260 mg/m2, d1 every 3 weeks

Locations

Country	Name	City	State
China	Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Provincial People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185. — View Citation

Provencio M, Nadal E, Insa A, Garcia-Campelo MR, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Casarrubios M, Salas Anton C, Parra ER, Wistuba I, Calvo V, Laza-Briviesca R, Romero A, Massuti B, Cruz-Bermudez A. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Nov;21(11):1413-1422. doi: 10.1016/S1470-2045(20)30453-8. Epub 2020 Sep 24. — View Citation

Reck M, Mok TSK, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Lee A, Coleman S, Deng Y, Kowanetz M, Shankar G, Lin W, Socinski MA; IMpower150 Study Group. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019 May;7(5):387-401. doi: 10.1016/S2213-2600(19)30084-0. Epub 2019 Mar 25. — View Citation

Shu CA, Gainor JF, Awad MM, Chiuzan C, Grigg CM, Pabani A, Garofano RF, Stoopler MB, Cheng SK, White A, Lanuti M, D'Ovidio F, Bacchetta M, Sonett JR, Saqi A, Rizvi NA. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):786-795. doi: 10.1016/S1470-2045(20)30140-6. Epub 2020 May 7. — View Citation

Zhang C, Chen HF, Yan S, Wu L, Yan LX, Yan XL, Yue DS, Xu CW, Zheng M, Li JS, Liu SY, Yang LL, Jiang BY, Ou QX, Qiu ZB, Shao Y, Wu YL, Zhong WZ. Induction immune-checkpoint inhibitors for resectable oncogene-mutant NSCLC: A multicenter pooled analysis. NPJ Precis Oncol. 2022 Sep 19;6(1):66. doi: 10.1038/s41698-022-00301-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Pathological Response (MPR)	Percentage of Participants with Major Pathologic Response. MPR was defined as percentage of tumor cells within tumor bed less than 10% for primary lung lesions.	MPR will be assessed within 2 weeks after surgery
Secondary	Objective Response Rate (ORR)	ORR is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.	Tumor response will be evaluated within 3-4 weeks after last dose of neoadjuvant treatment
Secondary	Pathological Complete Response (pCR)	Evaluation of the pathological complete response: The pathological complete response is defined as the absence of residual tumor in both lung and lymph nodes after neoadjuvant treatment.	pCR will be assessed within 2 weeks after surgery
Secondary	Progression-free Survival (PFS)	The period after initiation of neoadjuvant treatment when no disease progression can be detected.	From date of initiation of neoadjuvant treatment till the date of first documented disease progression or death, whichever came first, assessed up to 36 months.
Secondary	Overall Survival (OS)	The period after initiation of neoadjuvant treatment when no all-cause death can be detected.	From date of initiation of neoadjuvant treatment till the date of all-cause death, assessed up to 60 months.
Secondary	Adverse Events (AEs)	Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment	From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.