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Neoadjuvant Immunotherapy in EGFR-mutant Localized NSCLC (NEOTIDE)

Primary Purpose

Non-small Cell Lung Cancer, EGFR Activating Mutation

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Sintilimab

Carboplatin

Nab paclitaxel

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Neoadjuvant immunotherapy, Non-small cell lung cancer, EGFR mutation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age :18 Years to 75 Years;
ECOG physical score 0-1 points; expected survival time ≥ 3 months;
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;
At least one measurable target lesion according to the RECIST 1.1 standard;
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;
Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.

Exclusion Criteria:

Stage I and stage IV NSCLC;
Large panel NGS indicated ALK fusion or any other driver mutations;
Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
Patients who have previously used any other anti-tumor drugs or radiotherapy;
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;
Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections;
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;
Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
Patients with low compliance or willingness to take the drugs and surveillance.

Sites / Locations

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sintilimab plus chemo

Arm Description

3 cycles of neoadjuvant Sintilimab (200mg every 3 weeks) with nab-paclitaxel and carboplatin (nab-paclitaxel 260 mg/m2, d1 and carboplatin AUC 5, d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including EGFR-TKIs for up to 1 year or till disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Progression-free Survival (PFS)

The period after initiation of neoadjuvant treatment when no disease progression can be detected.

Overall Survival (OS)

The period after initiation of neoadjuvant treatment when no all-cause death can be detected.

Adverse Events (AEs)

Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment

Full Information

NCT ID

NCT05244213

First Posted

February 8, 2022

Last Updated

May 16, 2023

Sponsor

Guangdong Provincial People's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05244213

Brief Title

Neoadjuvant Immunotherapy in EGFR-mutant Localized NSCLC

Acronym

NEOTIDE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 4, 2022 (Actual)

Primary Completion Date

June 1, 2024 (Anticipated)

Study Completion Date

December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Guangdong Provincial People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer, EGFR Activating Mutation

Keywords

Neoadjuvant immunotherapy, Non-small cell lung cancer, EGFR mutation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

A Simon two-stage design was applied. Primary endpoint for this study was MPR. The unacceptable response rate for MPR was less than 10% and desirable response rate was 30%. The error rate for alpha was set as 0.05 and 0.1 for beta. The Optimal assay was chosen and at least 35 patients should be enrolled to meet adequate statical power. 18 patients would be enrolled in stage I and at least 2 patient achieved MPR were required to proceed stage II enrollment. Overall, if 6 achieved MPR out of 35 patients, the study would be determined as positive.

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sintilimab plus chemo

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Sintilimab

Intervention Description

200mg Q3W

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

AUC 5, d1 every 3 weeks

Intervention Type

Drug

Intervention Name(s)

Nab paclitaxel

Intervention Description

260 mg/m2, d1 every 3 weeks

Primary Outcome Measure Information:

Title

Major Pathological Response (MPR)

Description

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.

Time Frame

MPR will be assessed within 2 weeks after surgery

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

Time Frame

Tumor response will be evaluated within 3-4 weeks after last dose of neoadjuvant treatment

Title

Pathological Complete Response (pCR)

Description

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.

Time Frame

pCR will be assessed within 2 weeks after surgery

Title

Progression-free Survival (PFS)

Description

The period after initiation of neoadjuvant treatment when no disease progression can be detected.

Time Frame

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.

Title

Overall Survival (OS)

Description

The period after initiation of neoadjuvant treatment when no all-cause death can be detected.

Time Frame

From date of initiation of neoadjuvant treatment till the date of all-cause death, assessed up to 60 months.

Title

Adverse Events (AEs)

Description

Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment

Time Frame

From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age :18 Years to 75 Years; ECOG physical score 0-1 points; expected survival time ≥ 3 months; 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; At least one measurable target lesion according to the RECIST 1.1 standard; 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; Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up. Exclusion Criteria: Stage I and stage IV NSCLC; Large panel NGS indicated ALK fusion or any other driver mutations; Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer); Patients who have previously used any other anti-tumor drugs or radiotherapy; 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; Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections; 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; Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures; Patients with low compliance or willingness to take the drugs and surveillance.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wen-zhao Zhong, PhD

Phone

+86 20 83827812

Ext

51221

syzhongwenzhao@scut.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Chao Zhang, PhD

15920473691@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wen-zhao Zhong, PhD

Organizational Affiliation

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chao Zhang, PhD

15920473691@163.com

First Name & Middle Initial & Last Name & Degree

Wen-zhao Zhong, PhD

syzhongwenzhao@scut.edu.cn

First Name & Middle Initial & Last Name & Degree

Wen-zhao Zhong, PhD

First Name & Middle Initial & Last Name & Degree

Chao Zhang, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

After the primary data including translational analysis has been published, IPD of detailed clinical information and comics data could be available from principle investigator upon reasonable request.

IPD Sharing Time Frame

After the primary data including translational analysis has been published, IPD of detailed clinical information and comics data could be available. Approximate 48 months after initiation of enrollment.

IPD Sharing Access Criteria

IPD could be accessed from principle investigator upon reasonable request.

Citations:

PubMed Identifier

32386568

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.

Results Reference

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PubMed Identifier

32979984

Citation

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Results Reference

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PubMed Identifier

29658848

Citation

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.

Results Reference

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PubMed Identifier

30922878

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.

Results Reference

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PubMed Identifier

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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.

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Neoadjuvant Immunotherapy in EGFR-mutant Localized NSCLC

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