Study Evaluating Efficacy and Safety of Capmatinib in Combination With Osimertinib in Adult Subjects With Non-small Cell Lung Cancers as Second Line Therapy

Carcinoma, Non-Small-Cell Lung Clinical Trial

— GEOMETRY-E  

Official title:

A Phase III Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib in Combination With Osimertinib Versus Platinum - Pemetrexed Based Doublet Chemotherapy in Patients With Locally Advanced or Metastatic NSCLC Harboring EGFR Activating Mutations Who Have Progressed on Prior Generation EGFR-TKI Therapy and Whose Tumors Are T790M Mutation Negative and Harbor MET Amplification (GEOMETRY-E)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04816214
• Other study ID #: CINC280L12301
• Secondary ID: 2020-003677-21
• Status: Terminated
• Phase: Phase 3
• Start date: September 22, 2021
• Est. completion date: December 27, 2022

Study information

• Verified date: March 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aimed to evaluate the anticancer activity of capmatinib in combination with osimertinib compared to platinum-pemetrexed based doublet chemotherapy as second line treatment in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who progressed following EGFR tyrosine kinase inhibitors (TKIs).

Description:

This was a multicenter, open-label, randomized, active-controlled, global phase III study that enrolled adult participants with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) activating mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who had progressed following EGFR tyrosine kinase inhibitors (TKIs). The study was conducted in two parts. The initial part was a safety run-in part, which aimed at assessing the safety and tolerability of capmatinib in combination with osimertinib and at determining the recommended dosage for the subsequent randomized part. The randomized part compared the efficacy and safety of capmatinib in combination with osimertinib to a platinum-based doublet chemotherapy regimen using either cisplatin or carboplatin, combined with pemetrexed, as second-line treatment.The randomized part was not initiated. In the randomized part (if initiated), participants were to receive their assigned treatment (either capmatinib in combination with osimertinib or platinum-pemetrexed based doublet chemotherapy) until they experienced any of the following: documented disease progression according to the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) as assessed by the investigator during the run-in part and confirmed by a blinded independent review committee (BIRC) during the randomized part, withdrawal of consent, pregnancy, lost to follow-up, or death. Participants who progressed in the platinum-pemetrexed arm were to be permitted to switch to capmatinib in combination with osimertinib therapy after BIRC-confirmed, RECIST 1.1-defined progressive disease. If, in the judgment of the investigator, there was evidence of clinical benefit and the participant wished to continue, study treatment could be continued beyond the initial disease progression according to RECIST 1.1 criteria. After treatment discontinuation, all participants were to be followed for safety evaluations during the safety follow-up period. On 11-May-2022, Novartis decided to halt enrollment for this study due to a business consideration unrelated to any safety concerns. Ongoing patients in the run-in part were allowed to continue treatment through other post-trial drug supply options, as applicable. On 27-Dec-2022 the last patient was transitioned off the study, and following the study protocol this date was declared the Global end of trial date. Randomized part was not initiated.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: December 27, 2022
• Est. primary completion date: December 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations known to be associated with EGFR TKI sensitivity, EGFR T790M negative and MET gene amplification
• Stage IIIB/IIIC or IV NSCLC
• Participants must have progressed on one prior line of therapy (1st/2nd generation EGFR TKIs, osimertinib or other third generation EGFR TKIs) for advanced/metastatic disease (stage IIIB/IIIC and must be candidates for platinum (cisplatin or carboplatin) - pemetrexed doublet based chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Participants must have recovered from all toxicities related to prior systemic therapy to grade = 1 Common Terminology Criteria Adverse Event 5.0 (CTCAE v 5.0)
• At least one measurable lesion as defined by RECIST 1.1
• Participants must have adequate organ function

Key Exclusion Criteria:

• Prior treatment with any MET inhibitor or HGF-targeting therapy
• Participants with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms
• Carcinomatous meningitis
• Presence or history of a malignant disease other than NSCLC that had been diagnosed and/or required therapy within the past 3 years
• Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
• Clinically significant, uncontrolled heart diseases
• known druggable molecular alterations that may render participants eligible for alternative targeted therapies

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Capmatinib
Capmatinib was available as a film-coated tablet for oral use, with a strength of either 150 mg or 200 mg. The initial dose of the combination therapy consisted of capmatinib 400 mg administered orally twice daily (b.i.d).
• Osimertinib
Osimertinib was available as a tablet for oral use, with a strength of either 80 mg or 40 mg. The initial dose of the combination therapy consisted of osimertinib 80 mg administered orally once per day (q.d)
• Pemetrexed
Pemetrexed concentrate for solution for intravenous use was to be administered intravenously. The procurement of pemetrexed was to be done locally, following local practices and regulations.
• Cisplatin
Cisplatin concentrate for solution for intravenous use was to beadministered intravenously during the study. The procurement of cisplatin was to be done locally, following local practices and regulations.
• Carboplatin
Carboplatin concentrate for solution for intravenous use was to be administered intravenously during the study. The procurement of carboplatin was to be done locally, following local practices and regulations.

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Kashiwa	Chiba
Japan	Novartis Investigative Site	Sunto Gun	Shizuoka
Korea, Republic of	Novartis Investigative Site	Seoul
Singapore	Novartis Investigative Site	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)	A DLT was defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, progressive disease, inter-current illness, or concomitant medications, that despite optimal therapeutic intervention that occurred within the first 21 days of treatment with capmatinib in combination with osimertinib.	Up to 21 Days
Primary	Randomized Part: Progression Free Survival (PFS) Based on BIRC Assessment	PFS was defined as time from date of randomization to the date of first documented disease progression (PD) based on Blinded Independent Review Committee (BIRC) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurred first. Progression was defined as a =20% increase in sum of longest diameters (SLD) compared to smallest SLD in the study, or progression of non-target lesions or new lesions.	From randomization to first documented progression or deaths, planned to be assessed up to 37 months
Secondary	Run-in Part: Number of Participants With at Least One Dose Interruption and Dose Reduction of Each Study Drug	Number of participants with at least one dose interruption and dose reduction were reported for each study drug.	From the first dose until last dose of study treatment, assessed up to 39 weeks
Secondary	Run-in Part: Dose Intensity of Each Study Drug	Dose intensity was computed as the ratio of actual cumulative dose (milligrams) received and actual duration of exposure (weeks) to study drug.	From the first dose until last dose of study treatment, assessed up to 39 weeks
Secondary	Run-in Part: Median Duration of Exposure to Each Study Drug	Duration of exposure is defined as the time (in weeks) between the first and the last dose of study treatment.	From the first dose until last dose of study treatment, assessed up to 39 weeks
Secondary	Run-in Part: Maximum Plasma Concentration (Cmax) of Capmatinib	Blood samples were collected. Cmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.; Actual recorded sampling times were considered for the calculations	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
Secondary	Run-in Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)	Blood samples were collected. Cmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
Secondary	Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Capmatinib	Blood samples were collected. Tmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.; Actual recorded sampling times were considered for the calculations	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
Secondary	Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)	Blood samples were collected. Tmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.; Actual recorded sampling times were considered for the calculations	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
Secondary	Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Capmatinib	Blood samples were collected. AUClast of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
Secondary	Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)	Blood samples were collected. AUClast of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
Secondary	Run-in Part: Overall Response Rate (ORR) as Per Investigator Assessment	ORR was defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator judgment and according to RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in the SLD of the target lesions or no new lesions or no progression of non-target lesions.	Up to end of study, assessed up to 39 weeks
Secondary	Run-in Part: Duration of Response (DOR) as Per Investigator Assessment	DOR was defined as the time from first documented response of CR or PR to the date of first documented PD or death due to any cause. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in the SLD of the target lesions or no new lesions or no progression of non-target lesions; PD: =20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.	Up to disease progression or death or end of study, assessed up to 39 weeks
Secondary	Run-in Part: Time to Response (TTR) as Per Investigator Assessment	TTR was defined as the duration of time between the date of fist dose of treatmwnr and the date of the first documented response of either CR or PR as per investigator judgment and according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions.	From first dose of treatment up to end of study, assessed up to 39 weeks
Secondary	Run-in Part: Disease Control Rate (DCR) as Per Investigator Assessment	DCR was defined as the percentage of participants with a BOR of CR, PR, and stable disease (SD) as per investigator judgment and according to RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; SD: Neither sufficient shrinkage to qualify for PR or CR nor and increase in lesions which would qualify for PD. PD: =20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.	From randomization up to end of study, assessed up to 39 weeks
Secondary	Run-in Part: Progression-Free Survival (PFS) as Per Investigator Assessment	PFS was defined as the time (in months) from first dose of treatment to the date of the first documented progression or death due to any cause as per investigator judgment and according to RECIST v1.1. Progression was defined as a =20% increase in SLD compared to smallest SLD in the study, or progression of non-target lesions or new lesions. PFS was censored if no PFS event (progression or death) was observed.	From first dose of treatment until first documented progression or death or end of study, assessed up to 39 weeks
Secondary	Randomized Part: Overall Response Rate (ORR) as Per BIRC Assessment	ORR was defined as the percentage of participants with confirmed BOR of CR or PR, as per BIRC by RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions.	Planned to be assessed up to 37 months
Secondary	Randomized Part: Overall Intracranial Response Rate (OIRR) as Per BIRC Assessment	OIRR was defined as the percentage of participants with a confirmed best overall intracranial response (BOIR) of CR or PR as per BIRC according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids. PR: =30% decrease in the SLD of CNS target lesions or no new lesions or and stable to decreased corticosteroid dose.	Planned to be assessed up to 37 months
Secondary	Randomized Part: Duration of Response (DOR) as Per BIRC Assessment	DOR was defined as the time from the first documented response of CR or PR to the date of first documented progression or death as per BIRC according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; PD: =20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.	From first documented response to first documented progression or death, planned to be assessed up to 37 months
Secondary	Randomized Part: Time to Response (TTR) as Per BIRC Assessment	TTR was defined as duration of time between the date of randomization and the date of first documented response of either CR or PR as per BIRC according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions.	From randomization to first documented response, planned to be assessed up to 37 months
Secondary	Randomized Part: Disease Control Rate (DCR) as Per BIRC Assessment	DCR was defined as the percentage of participants with CR or PR or SD as per BIRC according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: =30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; SD: Neither sufficient shrinkage to qualify for PR or CR nor and increase in lesions which would qualify for PD. PD: =20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.	Planned to be assessed up to 37 months
Secondary	Randomized Part: Progression-Free Survival After Next Line of Treatment (PFS2) as Per Investigator Assessment	PFS2 was defined as the time from date of randomization to the first documented progression on the next line therapy as per investigator judgment according to RECIST v1.1 response criteria or death due to any cause.	Planned to be assessed up to 37 months
Secondary	Randomized Part: Maximum Plasma Concentration (Cmax) of Capmatinib	Cmax of capmatinib calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.	Pre-dose on Day 1 of Cycles 1, 2, 3, 4 and 6 (Cycle = 21 days)
Secondary	Randomized Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites	Cmax of osimertinib and its metabolites (AZ5104 and AZ7550) calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.	Pre-dose on Day 1 of Cycles 1, 2, 3, 4 and 6 (Cycle = 21 days)
Secondary	Randomized Part: Overall Survival (OS)	OS was defined as the time from date of randomization to date of death due to any cause.	From randomization to date of death, planned to be assessed up to 37 months
Secondary	Randomized Part: Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (EORTC QLQ-C30) Score	EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. It contains 30 items and is composed of both multi-item scales and single-item measures based on the participant's experience over the past week. These include five scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/quality of life scale (QoL) scale. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high /healthy level of functioning; a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology/problems.	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)
Secondary	Randomized Part: Change From Baseline in the EORTC QLQ Lung Cancer Module (EORTC QLQ-LC13) Score	EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms.	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)
Secondary	Randomized Part: Change From Baseline in the EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score	EQ-5D-5L is a standardized measure of health status developed by the EuroQol (EQ) Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The questionnaire also includes a Visual Analogue Scale (VAS), where the participant is asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state.	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)
Secondary	Randomized Part: Change From Baseline in the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy (NCCN FACT)-Brain Symptom Index Version 2.0 (FBrSI)	The NCCN FACT-Brain Symptom Index version 2.0 (FBrSI) is a questionnaire used to explore changes in symptoms associated with potential brain metastases (BM). The symptoms module contains 12 items with a recall period of the past 7 days. The participant responds to 12 statements and indicates to what extent it applies to them on a 5-point Likert response scale from "not at all"=0 to "very much"=4. Higher scores indicates a greater impact of symptoms on the participant's quality of life.	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)
Secondary	Randomized Part: Time to Symptom Deterioration for EORTC QLQ-C30 Questionnaire	Time to symptom deterioration from baseline from baseline for participant scores from the EORTC QLQ-C30 questionnaire. EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. It contains 30 items and is composed of both multi-item scales and single-item measures based on the participant's experience over the past week. These include five scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/quality of life scale (QoL) scale. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high /healthy level of functioning; a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology/problems.	From baseline to symptom deterioration, planned to be assessed up to 37 months
Secondary	Randomized Part: Time to Symptom Deterioration for EORTC QLQ-LC13 Questionnaire	Time to symptom deterioration from baseline for participant scores from EORTC QLQ-LC13 questionnaire. EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms.	From baseline to symptom deterioration, planned to be assessed up to 37 months
Secondary	Randomized Part: Time to Symptom Deterioration for NCCN FBrSl Questionnaire	Time to symptom deterioration from baseline for participant scores from the NCCN FBrSl questionnaire. The NCCN FACT-Brain Symptom Index version 2.0 (FBrSI) is a questionnaire used to explore changes in symptoms associated with potential brain metastases (BM). The symptoms module contains 12 items with a recall period of the past 7 days. The participant responds to 12 statements and indicates to what extent it applies to them on a 5-point Likert response scale from "not at all"=0 to "very much"=4. Higher scores indicates a greater impact of symptoms on the participant's quality of life.	From baseline to symptom deterioration, planned to be assessed up to 37 months
Secondary	Randomized Part: Duration of Intracranial Response (DOIR) Based on BIRC	DOIR was defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression per RANO-BM criteria as assessed by BIRC review or the date of death due to any cause. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids; PR: =30% decrease in the SLD of CNS target lesions or no new lesions, and stable to decreased corticosteroid dose.	From the date of first documented intracranial response to first documented intracranial progression or death, planned to be assessed up to 37 months
Secondary	Randomized Part: Time to Intracranial Response (TTIR) Based on BIRC	TTIR was defined as the time from the date of randomization to the date of the first documented intracranial response of either CR or PR as per BIRC according to RANO-BM criteria. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids; PR: =30% decrease in the SLD of CNS target lesions or no new lesions, and stable to decreased corticosteroid dose.	From randomization to first documented response, planned to be assessed up to 37 months
Secondary	Randomized Part: Intracranial Disease Control Rate (IDCR) Based on BIRC	IDCR was defined as the percentage of participants with a confirmed BOIR of CR or PR or SD as per BIRC according to RANO-BM criteria. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids; PR: =30% decrease in the SLD of CNS target lesions or no new lesions, and stable to decreased corticosteroid dose; SD: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.	Planned to be assessed up to 37 months

External Links

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