Trial Outcomes & Findings for Atezolizumab in Combination With Carboplatin Plus Pemetrexed in Chemotherapy-naïve Patients With Asymptomatic Brain Metastasis (NCT NCT03526900)
NCT ID: NCT03526900
Last Updated: 2024-10-09
Results Overview
Percentage of subjects without disease progression (intracranial or systemic) at 12 weeks after enrollment. Determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively. Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:Complete Response(CR),Disappearance of all target lesions; Partial Response (PR) ≥30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) ≥20% increase in the sum of diameters of target lesions. Reponse Evaluation criteria in brain metastasis (RANO) for target lesions assessed by MRI: Complete Response (CR) Disappearance of all CNS target lesions without use of corticosteroids, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions;Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions
COMPLETED
PHASE2
40 participants
12 weeks after enrollment
2024-10-09
Participant Flow
Screening details:Patients who are chemotherapy naïve and have Stage IV non-squamous NSCLC with untreated brain metastases will be enrolled in this study. Study enrollment was completed between November 2018 and December 2019.
Participant milestones
| Measure |
Atezolizumab
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
40
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Atezolizumab in Combination With Carboplatin Plus Pemetrexed in Chemotherapy-naïve Patients With Asymptomatic Brain Metastasis
Baseline characteristics by cohort
| Measure |
Atezolizumab
n=40 Participants
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
Age, Continuous
|
66.75 years
STANDARD_DEVIATION 14.2 • n=99 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
Spain
|
40 participants
n=99 Participants
|
|
Performance Status
ECOG 0
|
14 participants
n=99 Participants
|
|
Performance Status
ECOG 1
|
26 participants
n=99 Participants
|
|
Performance Status
ECOG 2
|
0 participants
n=99 Participants
|
|
Performance Status
ECOG 3
|
0 participants
n=99 Participants
|
|
Performance Status
ECOG 4
|
0 participants
n=99 Participants
|
|
Cigarrette Smoking History
Never Smoke
|
6 Participants
n=99 Participants
|
|
Cigarrette Smoking History
Former Smoke
|
11 Participants
n=99 Participants
|
|
Cigarrette Smoking History
Smoker
|
23 Participants
n=99 Participants
|
|
Histology
Adenocarcinoma
|
39 Participants
n=99 Participants
|
|
Histology
Adenosquamous
|
0 Participants
n=99 Participants
|
|
Histology
Squamous
|
0 Participants
n=99 Participants
|
|
Histology
Large Cell Carcinoma
|
0 Participants
n=99 Participants
|
|
Histology
NOS/Undifferentiated
|
1 Participants
n=99 Participants
|
|
PD-L1 expression
≥ 50%
|
10 Participants
n=99 Participants
|
|
PD-L1 expression
1%-49 %
|
10 Participants
n=99 Participants
|
|
PD-L1 expression
0 %
|
18 Participants
n=99 Participants
|
|
PD-L1 expression
Unknown
|
2 Participants
n=99 Participants
|
|
Baseline corticosteroids
Yes
|
22 Participants
n=99 Participants
|
|
Baseline corticosteroids
No
|
18 Participants
n=99 Participants
|
|
Diagnosis of brain metastases
Synchronous
|
37 Participants
n=99 Participants
|
|
Diagnosis of brain metastases
Metachronous
|
3 Participants
n=99 Participants
|
|
Total number of brain lesions per patient
|
5 Number of lesions
n=99 Participants
|
|
Total number of target brain lesions per patient
|
1 Number of lesions
n=99 Participants
|
PRIMARY outcome
Timeframe: 12 weeks after enrollmentPopulation: Intention-to-treat population cohort of 40 patients
Percentage of subjects without disease progression (intracranial or systemic) at 12 weeks after enrollment. Determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively. Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:Complete Response(CR),Disappearance of all target lesions; Partial Response (PR) ≥30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) ≥20% increase in the sum of diameters of target lesions. Reponse Evaluation criteria in brain metastasis (RANO) for target lesions assessed by MRI: Complete Response (CR) Disappearance of all CNS target lesions without use of corticosteroids, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions;Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions
Outcome measures
| Measure |
Atezolizumab
n=40 Participants
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
Efficacy of Atezolizumab + CBDCA + Pemetrexed by Evaluating PFS Rate
|
62.2 percentage of participants
Interval 47.1 to 76.2
|
SECONDARY outcome
Timeframe: Two consecutive evaluations 6 weeks apartObjective response defined as a complete response or partial response on two consecutive evaluations 6 weeks apart, as determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively. Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR) ≥30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) ≥20% increase in the sum of diameters of target lesions. Reponse Evaluation criteria in brain metastasis (RANO) for target lesions assessed by MRI: Complete Response (CR), Disappearance of all CNS target lesions without use of corticosteroids, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions; Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions or the appearance of new lesions
Outcome measures
| Measure |
Atezolizumab
n=40 Participants
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
Efficacy of Atezolizumab + CBDCA + Pemetrexed by Measuring Objective Response.
|
18 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.Population: Intention to treat
To record the number of patients best response with steroid vs without steroid. Response Evaluation criteria in brain metastasis (RANO-BM) for target lesions and assessed by MRI: Complete Response (CR) Disappearance of all CNS target lesions, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions; Overall Response (OR) = CR + PR. Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Atezolizumab
n=38 Participants
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
Overall Response by RANO Criteria and Steroids
No steroids Stable disease or progression
|
11 Participants
|
|
Overall Response by RANO Criteria and Steroids
No steroids Complete response or partial response
|
7 Participants
|
|
Overall Response by RANO Criteria and Steroids
Yes steroids Stable disease or progression
|
10 Participants
|
|
Overall Response by RANO Criteria and Steroids
Yes steroids Complete response or partial
|
10 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From date of randomization until the date of first needed salvage therapy, assessed up to 48 months.Population: Per protocol population
Register the median time to needed brain radiotherapy (WBRT or SRS).
Outcome measures
| Measure |
Atezolizumab
n=24 Participants
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
Median Time to Brain Radiotherapy (WBRT or SRS)
|
10.9 months
Interval 7.8 to 15.9
|
Adverse Events
Atezolizumab
Serious adverse events
| Measure |
Atezolizumab
n=40 participants at risk
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
Renal and urinary disorders
Nephritis
|
2.5%
1/40 • Number of events 1 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.0%
2/40 • Number of events 2 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Renal and urinary disorders
Acute kidney injury
|
5.0%
2/40 • Number of events 2 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Vascular disorders
Pulmonary embolism
|
2.5%
1/40 • Number of events 1 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.5%
1/40 • Number of events 1 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
Other adverse events
| Measure |
Atezolizumab
n=40 participants at risk
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Atezolizumab: - Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
-Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
|
|---|---|
|
General disorders
Anemia
|
20.0%
8/40 • Number of events 8 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
General disorders
Fatigue
|
37.5%
15/40 • Number of events 15 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Gastrointestinal disorders
Diarrhea
|
10.0%
4/40 • Number of events 4 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
General disorders
Anorexia
|
10.0%
4/40 • Number of events 4 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
7.5%
3/40 • Number of events 3 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Hepatobiliary disorders
Alanine aminotransferase increased
|
5.0%
2/40 • Number of events 2 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
5.0%
2/40 • Number of events 2 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
5.0%
2/40 • Number of events 2 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
|
Hepatobiliary disorders
Lipase increased
|
5.0%
2/40 • Number of events 2 • 48 months
The severity of AE will be determined using CTCAE version 4.03
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place