臨床研究等提出・公開システム

A phase II study of carboplatin and etopside plus durvalumab for previously-untreated extensive-stage small-cell lung cancer (ES-ECLC) patients with poor performance status (PS) (NEJ045A)

(NEJ045A)

57

Baseline Characteristics The safety set consists of 56 patients, including 43 patients in PS 2 and 13 patients in PS 3. In safety set, the median age was 73.5 years (Interquartile range [IQR] 69-77.5). Female accounted for 21% (12 patients). 21 patients were current smokers, and the other 35 patients were former smokers. 55 patients were with small cell lung cancer (SCLC), and the other patient was with combined SCLC. According to the TNM classification, 18 cases were classified as stage IVA, whereas 38 cases were classified as stage IVB.

This study was initially announced on jRCT on 31st January 2021, however, the first participant enrolled on 8th April 2021. The registration of participants had been delayed more than originally anticipated, therefore the period of the enrollment was extended to 30th November 2023 by 10 months. A total of 57 patients were enrolled by 3rd October 2023 on which the final participant was registered. One patient was excluded from the safety set due to withdrawal of consent before participating in any protocol treatment. In accordance with the ineligible criteria by central monitoring, three patients were removed from the FAS. Per protocol analysis omitted four patients who did not adhere to major protocol requirements. The safety set, FAS, and PPS included 56, 53, and 49 patients, respectively.

During the clinical trial period, 24 reportable serious adverse events occurred, including 6 diseases/conditions requiring reporting to the CRB. All events were already known. One case of sepsis was reported to the CRB, and the report was approved on October 15th, 2021. Other events were reported in the periodic reports.

[Primary endpoint] (Tolerability) 26 patients in PS 2 (66.7%; 80% confidence interval [CI], 55.2-76.7; p < 0.001) and five patients in PS 3 (50.0%; 80% CI, 26.7-73.3; p = 0.008) within the PPS completed four cycles of induction therapy. The proportion of the patients who completed induction therapy exceeded the predefined threshold. [Secondary endpoint] 1)1-year survival rate The 1-year survival rates were 43.4% (80% CI, 34.1-53.1) overall, 50.0% (80% CI, 39.1-60.9) in PS 2 and 18.2% (80% CI, 5.0-41.6) in PS 3. 2) ORR The overall ORR in the FAS, as determined by central review, was 50.9% (95% CI, 36.8-64.9), with 52.4% (95% CI, 36.4-68.0) in PS 2 and 45.5% (95% CI, 16.8-76.6) in PS 3. 3)PFS The median PFS in the FAS was 4.7 months (95% CI, 4.0-5.9) overall, with 4.8(95% CI, 3.8-6.2) in PS 2 and 4.6 (95% CI, 3.8-6.2) in PS 3. 4)OS The median OS in the FAS was 9.0 months (95% CI, 5.1-14.1) overall, with 11.3 (95% CI, 6.7-16.1) in PS 2 and 5.1 (95% CI, 2.2-8.6) in PS 3. 5)Improvement of PS PS improved in 29 patients (55%; 95% CI, 40.4-68.4) overall, with 24 (57%; 95% CI, 41.0-72.3) in PS 2 and five (46%; 95% CI, 16.8-76.6) in PS 3 showing improvement post-treatment. 6)Safety As previously stated, treatment-related AEs of any grade occurred in all patients, with grade 3 or higher AEs reported in 52 patients (93%) in the safety set, including 40 (93%) in PS 2 and 12 (92%) in PS 3. The most common grade 3 or higher AEs included neutrophil count decreased (36 patients, 64%), white blood cell count decreased (24 patients, 43%), lymphocyte count decreased (17 patients, 30%), hyponatremia (10 patients, 18%), and FN (9 patients, 16%). Sepsis secondary to a urinary tract infection during induction is reported as the treatment-related death. All reported adverse events were previously known.

This study demonstrated the tolerability of ICI combined with chemotherapy in patients with ES-SCLC with poor PS, showing a favourable 1-year survival rate and supporting the integration of ICI in this challenging patient population.

Oct. 03, 2025

Sept. 28, 2025

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(25)00240-1/abstract

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs031200319

Watanabe Satoshi

Niigata University Medical and Dental Hospital

1-754, Asahimachidori, Chuouku, Niigata-city, Niigata

satoshi7@med.niigata-u.ac.jp

Nozaki Koichiro

Niigata University Medical and Dental Hospital

1-754, Asahimachidori, Chuouku, Niigata-city, Niigata

+81-25-368-9325

knozaki@med.niigata-u.ac.jp

Complete

Jan. 21, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Extensive stage small cell lung cancer proven by histology and/or cytology without indication of curative surgery or curative radiotherapy, 2) No prior cytotoxic chemotherapy or immunotherapy, 3) ECOG PS 2 or 3, 4) 20 years or older, 5)Measurable disease, as defined by RECIST ver 1.1, 6) adequate hematologic and end organ function,7) Written informed consent form.

1) History of interstitial lung disease, 2) Symptomatic CNS metastases, CNS metastases treated with corticosteroids, leptomeningeal disease, 3) Irradiation for primary tumor or target lesion defined by RECIST ver1.1, 4) Uncontrolled heart, lung, liver, renal diseases, 5) History of autoimmune diseases or immunodeficiency, 6) Patients with active hepatitis B or hepatitis C or positive for HIV test, 7) Men without an intention to use the measure for contraception or women who are pregnant, lactating, or intending to become pregnant during the study, 8) Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, 9) Malignancies other than NSCLC within 5 years, 10) Systemic steroid administration at a dose of more than 10 mg of prednisolone for 4 weeks or longer.

Both

extensive disease small cell lung cancer

Induction therapy: Durvalumab 1500 mg/body day1 + carboplatin (PS 2: AUC 4, PS 3: AUC 3) day1 + etoposide (PS 2: 80 mg/m2, PS 3: 60mg/m2) day1 q3 - 4w. The doses can be titrated according to adverse events in the previous cycle.
Maintenance therapy: Durvalumab 1500 mg/body day1 q4w.

Tolerability of durvalumab, carboplatin and etoposide

One year survival rate, safety, objective response rate, progression-free survival, overall survival, improvement rate of PS

+81-25-368-9343

Dec. 21, 2020

none