UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000021133 |
|---|---|
| Receipt number | R000024153 |
| Scientific Title | A randomized phase II study comparing nivolumab with the combination of carboplatin and pemetrexed for epidermal growth factor receptor (EGFR) mutants non-squamous non-small cell lung cancer acquired resistance to EGFR-tyrosine kinase inhibitor from causes other than T790M.(WJOG8515L) |
| Date of disclosure of the study information | 2016/02/22 |
| Last modified on | 2023/05/17 11:08:19 |
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Basic information
Public title
A randomized phase II study comparing nivolumab with the combination of carboplatin and pemetrexed for epidermal growth factor receptor (EGFR) mutants non-squamous non-small cell lung cancer acquired resistance to EGFR-tyrosine kinase inhibitor from causes other than T790M.(WJOG8515L)
Acronym
A randomized phase II study comparing nivolumab with the combination of CBDCA and PEM for EGFR mutants NSCLC acquired resistance to EGFR-TKI from causes other than T790M.(WJOG8515L)
Scientific Title
A randomized phase II study comparing nivolumab with the combination of carboplatin and pemetrexed for epidermal growth factor receptor (EGFR) mutants non-squamous non-small cell lung cancer acquired resistance to EGFR-tyrosine kinase inhibitor from causes other than T790M.(WJOG8515L)
Scientific Title:Acronym
A randomized phase II study comparing nivolumab with the combination of CBDCA and PEM for EGFR mutants NSCLC acquired resistance to EGFR-TKI from causes other than T790M.(WJOG8515L)
Region
| Japan |
Condition
Condition
Lung Cancer
Classification by specialty
| Medicine in general | Pneumology | Hematology and clinical oncology |
Classification by malignancy
Malignancy
Genomic information
YES
Objectives
Narrative objectives1
To evaluate the efficacy and safety of nivolumab comparing with CBDCA/PEM for EGFR mutants NSCLC acquired resistance to EGFR-TKI from causes other than T790M.
Basic objectives2
Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase
Phase II
Assessment
Primary outcomes
Progression free survival
Key secondary outcomes
Overall survival, Overall response rate, Duration of response, Rate of adverse events, Overall survival and progression free survival for PD-L1 status
Base
Study type
Interventional
Study design
Basic design
Parallel
Randomization
Randomized
Randomization unit
Individual
Blinding
Open -no one is blinded
Control
Active
Stratification
YES
Dynamic allocation
YES
Institution consideration
Institution is considered as adjustment factor in dynamic allocation.
Blocking
Concealment
Central registration
Intervention
No. of arms
2
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
biweekly 3mg/kg nivolumab treatment
Interventions/Control_2
Combination treatment with carboplatin (AUC = 6, *if the case over 75 years, AUC=5) + pemetrexed (500mg/m2) following with maintenance therapy with pemetrexed
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 20 | years-old | <= |
Age-upper limit
| 75 | years-old | > |
Gender
Male and Female
Key inclusion criteria
1) Subjects with histologically confirmed Stage IV or recurrent NSCLC with disease progression on therapy with more than 1 prior EGFR TKI therapy.
2) Evidence of A , B or C
A. Proven T790M negative in tissue samples by re-biopsy after prior EGFR-TKI treatment.
B. After proven T790M positive in tissue or plasma samples by re-biopsy after prior EGFR-TKI, showing disease recurrence or progression for administration of third generation EGFR-TKI.
C. Progression after third generation EGFR-TKI as an initial therapy.
3) Subjects with confirmed EGFR mutations (ie, G719X, L861Q, S768I, Del 19, and L858R)
4) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
5) Men and women above 20
Key exclusion criteria
1) Subjects with active, known or suspected autoimmune disease.
2) Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
3) Prior therapy with antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
4) Subjects with interstitial lung disease
5) Positive test for hepatitis B virus antigen or hepatitis C virus indicating acute or chronic infection
Target sample size
100
Research contact person
Name of lead principal investigator
| 1st name | Hidetoshi |
| Middle name | |
| Last name | Hayashi |
Organization
Kinki University, Faculty of Medicine
Division name
Department of Medical Oncology
Zip code
589-8511
Address
377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan
TEL
072-366-0221
hidet31@med.kindai.ac.jp
Public contact
Name of contact person
| 1st name | Shinichiro |
| Middle name | |
| Last name | Nakamura |
Organization
West Japan Oncology Group
Division name
WJOG datacenter
Zip code
556-0016
Address
Namba Plaza Bldg. 304-1-5-7, Motomachi Naniwa-ku, Osaka 556-0016 JAPAN
TEL
06-6633-7400
Homepage URL
datacenter@wjog.jp
Sponsor or person
Institute
West Japan Oncology Group
Institute
Department
Personal name
Funding Source
Organization
ONO PHARMACEUTICAL CO., LTD
Bristol-Myers Squibb
Organization
Division
Category of Funding Organization
Profit organization
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Kinki university institutional Review Board
Address
377-2, Ohnohigashi, Osaka-sayama, Osaka, Japan
Tel
072-366-0221
hidet31@med.kindai.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2016 | Year | 02 | Month | 22 | Day |
Related information
URL releasing protocol
https://jrct.niph.go.jp/latest-detail/jRCTs051180133
Publication of results
Published
Result
URL related to results and publications
https://pubmed.ncbi.nlm.nih.gov/34921023/
Number of participants that the trial has enrolled
102
Results
Brief summary Nivolumab was clearly inferior to standard platinum-combination chemotherapy with regard to PFS in EGFR-mutated NSCLC patients with acquired EGFR-TKI resistance. Nevertheless, a small proportion of such patients experienced a longer-term response to nivolumab, and biomarker analysis identified potential target molecules for future immunotherapy in this patient population.
Results date posted
| 2023 | Year | 05 | Month | 17 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
| 2021 | Year | 12 | Month | 26 | Day |
Baseline Characteristics
Nivolumab and carboplatin pemetrexed groups, respectively
Median age 70.5 years, 67 years
Females 53.8%, 62.0%
Never smokers 55.8%, 56.0%
Brain metastases 32.7%, 28.0%
EGFR mutation
Exon21 L858R 53.8%, 48.0%
Exon19 del 46.2%, 48.0%
Other 1.7%, 4.0%
PD-L1 expression status (0%/1-49%/>50%/unknown)
37%/19%/15%/29%, 54%/20%/6%/20%
Participant flow
102 patients with EGFR-mutated NSCLC who acquired EGFR-TKI resistance not due to a secondary T790M mutation of EGFR were randomized 1:1 to nivolumab (n=52) or carboplatin-pemetrexed (n=50).
Adverse events
AEs related to study treatment occurred in 60.8% (grade 3-5, 9.8%) and 82.0% (grade 3-5, 12.0%) of patients in the nivolumab and carboplatin-pemetrexed arms, respectively. The most common AEs of grade 3 or 4 were fatigue and skin toxicity (3.8% each) in the nivolumab arm and neutropenia (32.0%), anemia (28.0%), leukopenia (22.0%), and thrombocytopenia (16.0%) in the carboplatin-pemetrexed arm. Serious AEs were observed in 25.5% and 16.0% of patients in the nivolumab and carboplatin-pemetrexed arms, respectively. Treatment discontinuation due to AEs occurred in 3 patients in the nivolumab arm (2 with arthritis and 1 with bilirubin increased) and 7 patients in the carboplatin-pemetrexed arm (2 each with renal failure and hepatic dysfunction as well as 1 each with anaphylactic shock, severe fatigue, and thromboembolism). There was 1 case of treatment-related interstitial lung disease (ILD) of grade 1 in the nivolumab arm. Treatment-related death was not apparent in either arm.
Outcome measures
Median PFS and 1-year PFS probability were 1.7 months and 9.6% for nivolumab versus 5.6 months and 14.0% for carboplatin-pemetrexed [log-rank P < 001; hazard ratio (HR) of 1.92, with a 60% confidence interval (CI) of 1.61-2.29]. Overall survival was 20.7 and 19.9 months [HR = 0.88 (95% CI, 0.53-1.47)], and response rate was 9.6% and 36.0% for nivolumab and carboplatin-pemetrexed, respectively.
Adverse events were no different than in previous studies of the same treatment. Interstitial pneumonia was seen in only one patient in the nivolumab arm (G1).
No subgroup including patients with a high tumor mutation burden showed a substantially longer PFS with nivolumab than with carboplatin-pemetrexed. The T cell-inflamed gene expression profile score (0.11 versus - 0.17, P = 0.036) and expression of genes related to cytotoxic T lymphocytes or their recruitment were higher in tumors that showed a benefit from nivolumab.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2016 | Year | 02 | Month | 22 | Day |
Date of IRB
| 2016 | Year | 03 | Month | 16 | Day |
Anticipated trial start date
| 2016 | Year | 04 | Month | 12 | Day |
Last follow-up date
| 2021 | Year | 07 | Month | 09 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2016 | Year | 02 | Month | 22 | Day |
Last modified on
| 2023 | Year | 05 | Month | 17 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024153
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