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A phase II study of Atezolizumab for advanced / recurrent Non-Small Cell Lung Cancer with Idiopathic Interstitial Pneumonias (TORG1936 / AMBITIOUS study)

TORG1936 / AMBITIOUS study

17

A total of 17 patients were enrolled, median age was 70 years (58-81 years), 16 males and 1 female, 4 with PS 0 and 13 with PS 1. There were 14 cases of unresectable advanced cancer, 3 cases of postoperative recurrence. The histological types were adenocarcinoma in 9 cases, squamous cell carcinoma in 7 cases, and not otherwise specified in 1 case. 3 patients were current smokers, 14 patients had a smoking history, and 0 patients had no smoking history.

At the time of enrollment of 10 patients, the Efficacy and Safety Evaluation Committee was consulted regarding pneumonitis, and the decision was made that there was no problem in continuing the study. At the time of enrollment of 15 patients, 3 patients had pneumonitis with grade 3 or higher, and the principal investigator consulted the Efficacy and Safety Evaluation Committee for a decision to temporarily interrupt new enrollment. Two patients who had given consent at the time of the interruption were enrolled after the safety of the study was explained again and consent was obtained. Finally, the study was terminated after 17 patients were enrolled.

One patient died during the treatment period. This patient developed pneumonitis or acute exacerbation of pre-existing IP on day 35 after the initiation of treatment, and his respiratory condition deteriorated rapidly. death was confirmed on day 51. Two patients died of acute exacerbation of IP during the follow-up period. Fatal patient 1 developed pneumonia or acute exacerbation of IP during the treatment period and discontinued treatment. He recovered from the pneumonitis, but during the follow-up period, he developed an acute exacerbation of IP triggered by influenza infection and died. Fatal patient 2 received 3 regimens after discontinuation of the study treatment due to PD, and died of an acute exacerbation of IP more than one year after the last dose of the study treatment. Among the adverse events that occurred during the study treatment or within 30 days of the last dose of the study treatment in all 17 treated patients, pneumonitis/acute exacerbation of IP was Grade 2 in 1 case, Grade 3 in 3 cases, and Grade 5 in 1 case, with an incidence rate of 41.2% for all grades. In addition, the following incidences were reported: hypoalbuminemia: 94.1%, hyponatremia: 70.6%, anemia: 70.6%, increased AST: 64.7%, increased ALT: 58.8%, cough: 47.1%, and malaise, anorexia, fever, and increased ALP: 41.2% each.

In this study, we set the 1-year survival rate as the primary endpoint and investigated whether the lower limit of the 95% confidence interval (CI) of the 1-year survival rate was higher than the threshold of 15%. The 1-year survival rate in 16 FAS was 53.3% (95% CI: 25.9-74.6), indicating that the lower limit of the confidence interval exceeded the threshold. The median overall survival for the secondary endpoint was 15.3 months (95% CI: 3.1 months-NR). The incidence of pneumonitis / acute exacerbations of IP within 1 year of enrollment was 29.4% (95% CI: 10.3-56.0), and the incidence of death from pneumonitis / acute exacerbations of IP during the entire observation period was 17.6% (95% CI: 3.8-43.4).

Atezolizumab for NSCLC with comorbid interstitial pneumonia may provide survival benefit, despite the high risk of developing pneumonitis.

June. 28, 2022

June. 27, 2022

https://academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyac118/6618634?searchresult=1

No

We have no plans to share IPD data.

https://jrct.niph.go.jp/latest-detail/jRCTs031190084

KATO Terufumi

Kanagawa Cancer Center

2-3-2 Nakao, Asahi-ku, Yokohama

terufumikato@gmail.com

IKEDA Satoshi

Kanagawa Cardiovascular and Respiratory Center

6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama

+81-45-701-9581

isatoshi0112@gmail.com

Complete

Aug. 27, 2019

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1)Histologically or cytologically proven non-small cell lung cancer
2)Unresectable stage 3/4 or recurrent
3)Received prior chemotherapy including platinum doublet
4)Chronic fibrotic IP
HRCT revealed (1) reticular shadow with basal and peripheral predominance suggestive of UIP pattern,or(2) peri-bronchovascular shadow suggestive of NSIP pattern
lOther interstitial lung disease of known etiology(infection, pneumoconiosis, drug, sarcoidosis, and collagen vascular disease)
l%FVC>70%
l%DLCO>35%
5)Age>=20 years
6)ECOG Performance Status 0-1
7)With measurable or evaluable lesions according to RECIST Version1.1
8)Vital organ functions are preserved
9)Received sufficient explanations about the name and severity of the illness
10) Written informed consent

1)History of acute exacerbation of IPF
2)Treatment history with immune-checkpoint inhibitor
3)Systemic treatment with steroids at a daily dose>10mg of prednisolone equivalent or immunosupressants
4)Active autoimmune disease or history of autoimmune disease requiring treatment
5)Symptomatic brain metastasis or spinal cord metastases
6)Active viral hepatitis
7)Active infection
8)Synchronous or metachronous active double malignancies
9)Pregnant or breastfeeding
10) Disapprove of contraception during the protocol treatment period
11) Treatment history with thoracic radiotherapy
12) History of serious drug allergies
13) Other conditions not suitable for the study

Both

Advanced / recurrent Non-small cell lung cancer with idiopathic interstitial pneumonia

Atezolizumab 1200mg, every 3 weeks

1 year-survival rate

The incidence of acute exacerbation of IP within 1 year after treatment initiation, overall survival, progression free survival, objective response rate, time to treatment failure, mortality rate due to acute exacerbation of IP or pneumonitis during observation period, safety

+81-25-368-9343

July. 23, 2019

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