Neoadjuvant Immunotherapy in EGFR-mutant Localized NSCLC

NCT05244213 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: CTONG2104
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer; EGFR Activating Mutation

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Objective Response Rate (ORR)

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

• Pathological Complete Response (pCR)

  pCR will be assessed within 2 weeks after surgery

• Progression-free Survival (PFS)

  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.

• Overall Survival (OS)

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

• Adverse Events (AEs)

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

Study Arms (1)

Sintilimab plus chemo

EXPERIMENTAL

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.

Biological: Sintilimab; Drug: Carboplatin; Drug: Nab paclitaxel

Interventions

Sintilimab BIOLOGICAL

200mg Q3W

Sintilimab plus chemo

Carboplatin DRUG

AUC 5, d1 every 3 weeks

Sintilimab plus chemo

Nab paclitaxel DRUG

260 mg/m2, d1 every 3 weeks

Sintilimab plus chemo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (1)

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

Guangzhou, Guangdong, 510080, China

Location

Related Publications (5)

• 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.

  PMID: 32386568 BACKGROUND

• 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.

  PMID: 32979984 BACKGROUND

• 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.

  PMID: 29658848 BACKGROUND

• 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.

  PMID: 30922878 BACKGROUND

• 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.

  PMID: 36123526 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sintilimab; Carboplatin; Taxes

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Economics; Health Care Economics and Organizations

Study Officials

• Wen-zhao Zhong, PhD

  Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 17, 2022
• Study Start: June 4, 2022
• Primary Completion: June 5, 2024
• Study Completion: December 1, 2025
• Last Updated: July 8, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR, ANALYTIC CODE
• 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.
• Access Criteria: IPD could be accessed from principle investigator upon reasonable request.

Locations

CN (1)