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TerminatedNCT01870726Updated May 30, 2018Results posted

Safety and Efficacy of INC280 and Buparlisib (BKM120) in Patients With Recurrent Glioblastoma

A Phase 1/2 interventional study of INC280 and Buparlisib in c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM, sponsored by Novartis Pharmaceuticals. Terminated at 13 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-05-30.

Sponsored by Novartis Pharmaceuticals · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
43
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The study assessed the safety and the dose of the combination of INC280 and buparlisib (BKM120), as well as the anti-tumor activity of the combination, in patients with recurrent glioblastoma with PTEN mutations, homozygous deletion of PTEN or PTEN negative by IHC. In addition, the anti-tumor activity of INC280 single agent should have been assessed in patients with recurrent glioblastoma with c-Met alteration.

Read the detailed description

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD and/or to identify the recommended phase II dose (RP2D) for the combination of INC280 and buparlisib, followed by the phase II part to assess the clinical efficacy of INC280 single agent and in combination with buparlisib (BKM120), and to further assess the safety of the combination. In addition, a surgical arm should have started concurrently with the phase II part, to determine the PK/PD profile of the study drug combination in patients undergoing tumor resection for recurrent glioblastoma after 7 to 10-days treatment.

RP2D was not declared due to a lack of efficacy of the combination in the phase Ib stage, and phase II was continued with INC280 monotherapy only.

02

Conditions studied

  • c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM

Keywords

  • Glioblastoma multiforme (GBM), glioblastoma, Grade IV Astrocytoma, brain tumor, brain cancer, giant cell glioblastoma, gliosarcoma
03

In context

Glioblastoma

1,919 studies on the registry are indexed under Glioblastoma; 449 are open to participants now.

This study's enrollment of 43 is above the median of 36 across 1,617 interventional studies indexed under Glioblastoma.

Browse Glioblastoma studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • ≥ 18 years of age.
  • Histologically confirmed diagnosis of glioblastoma (after initial tumor resection or biopsy) with radiographic evidence of recurrent tumor per RANO criteria.
  • Phase Ib: Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score \<10) by IHC confirmed by local or central assessment.
  • Phase II: Documented evidence of c-Met amplification (GCN>5) (fusion transcripts or mutant c-Met may be eligible after discussion with Novartis) or PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score \<10) by central assessment.

  • Must have received the following treatment for glioblastoma:

    •Prior treatment with radiotherapy and temozolomide; Note: A maximum of two prior chemotherapy/antibody regimens (including bevacizumab or other direct VEFG/VEGFR inhibitors) for recurrent disease are permitted.

  • Representative archival tumor sample from glioblastoma (formalin-fixed paraffine embedded tissue) must be available.
  • ECOG performance status ≤ 2.
  • Able to swallow and retain oral medication.
  • Patients in the surgical arm only: patients with recurrent glioblastoma must be eligible for surgical resection as deemed by the site Investigator.

Exclusion criteria

Exclusion Criteria:

  • Prior or current treatment with a c-MET inhibitor or HGF-targeting therapy
  • Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma or for pre-existing neoplasm transformed to glioblastoma (applicable for combination treatment arm only)
  • Received radiation (including therapeutic radioisotopes such as strontium 89) therapy ≤ 3 months prior to the first dose of study treatment and have not recovered from side effects of such therapy (≤ Grade 1) prior to the first dose of study treatment, except for alopecia.
  • Receiving treatment with medications that are known strong inhibitors or inducers of CYP3A, and cannot be discontinued 7 days prior to the start of the treatment and during the course of the study.
  • Receiving treatment with medications that are known CYP3A, CYP1A2, CYP2C8, CYP2C9 or CYP2C19 substrates with narrow therapeutic index, and cannot be discontinued during the course of the study.
  • Receiving treatment with long acting proton pump inhibitors, and cannot be discontinued 3 days prior to the start of INC280 treatment and during the course of the study.
  • Currently receiving warfarin or other coumadin-derived anticoagulants for treatment, prophylaxis or otherwise.
  • Currently receiving increasing or chronic treatment ( > 5 days) with corticosteroids (e.g. dexamethasone > 4 mg/day or other corticosteroids equivalent dose) or another immunosuppressive agent.
  • History of acute or chronic pancreatitis or any risk factors that may increase the risk of pancreatitis.
  • Active cardiac disease or a history of cardiac dysfunction.
  • Impairment of gastrointestinal (GI) function or GI disease that might significantly alter the absorption of study drug
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM- IV).
  • Anxiety ≥ CTCAE grade 3

  • Any of the following baseline laboratory values:

    • Hemoglobin \< 9 g/dL
    • Platelet count \< 75 x 109/L
    • Absolute neutrophil count (ANC) \< 1.0 x 109/L
    • INR > 1.5
    • Serum lipase > normal limits for the institution
    • Asymptomatic serum amylase > grade 2
    • Potassium, magnesium, and calcium (corrected for albumin) > normal limits for the institution
    • Total bilirubin > 1.5 x ULN
    • Serum creatinine >1.5 x ULN or creatinine clearance ≤ 45 mL/min
    • Alanine aminotransferase (AST) or aspartate aminotransferase (ALT) > 3.0 x ULN (or \< 5.0 x ULN if liver metastases are present)
    • Fasting plasma glucose > 120mg/dL or > 6.7 mmol/L
    • HbA1c > 8%.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
43 participants (actual)

Study arms

  • Experimental
    Phase Ib

    To estimate the safe dose of the combination INC280 and buparlisib

    Drug: INC280 · Drug: Buparlisib

  • Experimental
    Phase II

    To estimate anti-tumor efficacy of INC280 single agent and in combination with buparlisib

    Drug: INC280

Interventions

  • DrugINC280

    Phase Ib: INC280 was given at the starting dose of 200mg capsules twice daily with escalation to higher strengths. Phase II: INC280 was given at the dose of 400mg (tablets) twice daily.

  • DrugBuparlisib

    Buparlisib was given at the starting dose of 50mg once daily with escalation to higher strengths.

    Also known as: BKM120

06

What researchers measure

Primary outcomes

  1. Number of Patients Reporting Dose Limiting Toxicities (DLTs) in Cycle 1

    A DLT is defined as an adverse event or abnormal laboratory value where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment (28 days) with INC280 in combination with buparlisib and meets any of the pre-defined criteria. The maximum tolerated dose was identified as INC280 300 mg BID + buparlisib 80 mg QD.

    Time frame: Cycle 1, 28 days

  2. Phase II: Progression Free Survival Rate (PFSR)

    Estimated rate of patients treated during 6 months without experiencing disease progression. The Progression Free Survival Rate at 6 months was to be estimated using a Bayesian model described in the protocol. The models operating characteristics were evaluated based on the enrollment of at least 30 patients enrolled. Patients did not reach the milestone for the PFSR analysis (trial terminated); as such no analysis was performed.

    Time frame: 6 months

  3. Phase II Surgical Arm: Concentrations of INC280 and Buparlisib in Tumor.

    Concentrations of INC280 and buparlisib in tumor tissue.

    Time frame: 7 days

Secondary outcomes

  1. Number of Participants With Adverse Events

    To characterize the safety of INC280 single agent and in combination with buparlisib including type, frequency, severity of adverse events, serious adverse events, and dose interruptions and adjustments. Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, unless otherwise specified. If CTCAE grading did not exist for an AE, the severity of mild, moderate, severe, and lifethreatening, corresponding to Grades 1 - 4, were used. CTCAE Grade 5 (death) was not used in this study but was collected as a seriousness criterion; rather, information about deaths was collected though a Death form.

    Time frame: throughout the duration of the trial, approximately 3 years from FPFV to LPLV

  2. Pharmacokinetic Profile of INC280 - AUCtau

    Plasma concentration profile of INC280 in combination with Buparlisib. AUCtau is the AUC from time zero to the end of dosing interval.

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  3. Pharmacokinetic Profile of INC280 - Cmax

    Plasma concentration profile of INC280 in combination with Buparlisib. Cmax is the Maximum (peak) observed drug concentration after dose administration.

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  4. Pharmacokinetic Profile of INC280 - Tmax

    Plasma concentration profile of INC280 in combination with Buparlisib. Tmax is the time to reach maximum (peak) observed concentration (Cmax) after dose administration

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  5. Pharmacokinetic Profile of INC280 - T1/2

    Plasma concentration profile of INC280 in combination with Buparlisib. T1/2 is the terminal half life

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  6. Pharmacokinetic Profile of Buparlisib - AUCtau

    Plasma concentration profile of Buparlisib in combination with INC280. AUCtau is the AUC from time zero to the end of dosing interval.

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  7. Pharmacokinetic Profile of Buparlisib - Cmax

    Plasma concentration profile of INC280 in combination with Buparlisib. Cmax is the Maximum (peak) observed drug concentration after dose administration.

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  8. Pharmacokinetic Profile of Buparlisib - Tmax

    Plasma concentration profile of INC280 in combination with Buparlisib. Tmax is the time to reach maximum (peak) observed concentration (Cmax) after dose administration

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  9. Pharmacokinetic Profile of Buparlisib - T1/2

    Plasma concentration profile of INC280 in combination with Buparlisib. T1/2 is the terminal half life

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months

  10. Best Overall Response (BOR)

    Best Overall Response (BOR) observed in the study population of INC280 Single Agent and in Combination with Buparlisib. Responses will be assessed by the investigators following the RANO criteria with MRI or CT scans scheduled every 8 weeks. Summary of the RANO response criteria: CR has no T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; PR has ≥50% decrease T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; SD has ≥50% decrease but \<25% increase T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; PD has ≥25% increase in T1-Gd+ (enhancing lesion), increase T2/FLAIR (non-enhancing lesion), presence of new lesion, deterioration in clinical status.

    Time frame: throughout the duration of the trial - approximately 3 years (from FPFV to LPLV)

  11. Overall Survival (OS)

    Survival rate of patients from start of treatment to date of death due to any cause. Patients did not reach the milestone for the survival data analysis (terminated early); as such no analysis was done.

    Time frame: throughout the duration of the trial - approximately 3 years (FPFV to LPLV)

07

Results

Posted May 24, 2018
Limitations and caveats
At the end of Phase Ib, it was decided not to enroll patients in the two Phase II arms evaluating INC280 with buparlisib. The phase II INC280 single agent arm was halted before it reached target enrollment.

Participant flow

Participant flow — Overall Study
Milestone200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab +80 mg QD400 mg BID Tab
Started56467510
Completed0000000
Not completed56467510
Withdrew: Withdrawal of informed consent0001000
Withdrew: Withdrawal by subject0100000
Withdrew: Adverse event0000110
Withdrew: Progressive disease55456410

Outcome measures

PrimaryNumber of Patients Reporting Dose Limiting Toxicities (DLTs) in Cycle 1

A DLT is defined as an adverse event or abnormal laboratory value where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment (28 days) with INC280 in combination with buparlisib and meets any of the pre-defined criteria. The maximum tolerated dose was identified as INC280 300 mg BID + buparlisib 80 mg QD.

Time frame:
Cycle 1, 28 days
Reported as:
Number · Number of Patients
Number of Patients Reporting Dose Limiting Toxicities (DLTs) in Cycle 1
Number of Patients200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Personality Change0 ± 1257.871 ± 2291.800 ± 2604.720 ± 2702.560 ± 2702.470 ± 5627.79
Nausea0 (4045.6 to 10405.8)0 (3069.8 to 13946.9)0 (6276.0 to 31532.5)0 (1940.8 to 3618.0)1 (8606.0 to 16381.0)0 (11576.1 to 17422.8)
Aspartate Aminotransferase Increased0 (3880.4 to 7192.8)0 (2655.6 to 2655.6)0 (19903.7 to 27092.8)0 (4793.3 to 14289.7)0 (7002.3 to 12184.7)2 (13051.1 to 13051.1)
PrimaryPhase II: Progression Free Survival Rate (PFSR)

Estimated rate of patients treated during 6 months without experiencing disease progression. The Progression Free Survival Rate at 6 months was to be estimated using a Bayesian model described in the protocol. The models operating characteristics were evaluated based on the enrollment of at least 30 patients enrolled. Patients did not reach the milestone for the PFSR analysis (trial terminated); as such no analysis was performed.

Time frame:
6 months

No measurements were reported for this outcome.

PrimaryPhase II Surgical Arm: Concentrations of INC280 and Buparlisib in Tumor.

Concentrations of INC280 and buparlisib in tumor tissue.

Time frame:
7 days

No measurements were reported for this outcome.

SecondaryNumber of Participants With Adverse Events

To characterize the safety of INC280 single agent and in combination with buparlisib including type, frequency, severity of adverse events, serious adverse events, and dose interruptions and adjustments. Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, unless otherwise specified. If CTCAE grading did not exist for an AE, the severity of mild, moderate, severe, and lifethreatening, corresponding to Grades 1 - 4, were used. CTCAE Grade 5 (death) was not used in this study but was collected as a seriousness criterion; rather, information about deaths was collected though a Death form.

Time frame:
throughout the duration of the trial, approximately 3 years from FPFV to LPLV
Reported as:
Number · Participants
Number of Participants With Adverse Events
Participants200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab + 80 mg QD400 mg BID Tab + 80 mg QD400 mg BID Tab
Adverse events5646759
Treatment-related AEs4444756
AEs with grade ≥ 35442548
SAEs3233342
AEs leading to discontinuation0000110
AEs leading to dose adjustment/interruption2324445
AEs requiring additional therapy4535757
SecondaryPharmacokinetic Profile of INC280 - AUCtau

Plasma concentration profile of INC280 in combination with Buparlisib. AUCtau is the AUC from time zero to the end of dosing interval.

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · hr*ng/ml
Pharmacokinetic Profile of INC280 - AUCtau
hr*ng/ml200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 12435.6 ± 1257.873005.9 ± 2291.804789.7 ± 2604.725071.7 ± 2702.565732.2 ± 2702.4711127.7 ± 5627.79
Cycle 1 Day 155749.3 (4045.6 to 10405.8)11261.7 (3069.8 to 13946.9)10581.0 (6276.0 to 31532.5)2779.4 (1940.8 to 3618.0)12801.3 (8606.0 to 16381.0)16590.6 (11576.1 to 17422.8)
Cycle 2 Day 14894.6 (3880.4 to 7192.8)2655.6 (2655.6 to 2655.6)23498.3 (19903.7 to 27092.8)10554.3 (4793.3 to 14289.7)9593.5 (7002.3 to 12184.7)13051.1 (13051.1 to 13051.1)
SecondaryPharmacokinetic Profile of INC280 - Cmax

Plasma concentration profile of INC280 in combination with Buparlisib. Cmax is the Maximum (peak) observed drug concentration after dose administration.

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · ng/ml
Pharmacokinetic Profile of INC280 - Cmax
ng/ml200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 1618.0 ± 509.47880.0 ± 481.70960.5 ± 898.05860.0 ± 1081.121990.0 ± 778.913635.0 ± 1499.76
Cycle 1 Day 151560.0 (745.0 to 2610.0)2005.0 (763.0 to 3930.0)3480.0 (1350.0 to 8350.0)545.5 (315.0 to 776.0)3610.0 (2320.0 to 4940.0)4850.0 (1800.0 to 5350.0)
Cycle 2 Day 11200.0 (578.0 to 1540.0)2142.5 (675.0 to 3610.0)5010.0 (4230.0 to 5790.0)2254.5 (479.0 to 3740.0)3080.0 (2720.0 to 3440.0)3220.0 (3220.0 to 3220.0)
SecondaryPharmacokinetic Profile of INC280 - Tmax

Plasma concentration profile of INC280 in combination with Buparlisib. Tmax is the time to reach maximum (peak) observed concentration (Cmax) after dose administration

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · hr
Pharmacokinetic Profile of INC280 - Tmax
hr200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 11.1 ± 509.472.0 ± 481.701.5 ± 898.051.3 ± 1081.121.6 ± 778.912.0 ± 1499.76
Cycle 1 Day 151.9 (0.9 to 2.0)2.0 (1.0 to 2.1)2.0 (1.0 to 2.1)2.6 (1.2 to 4.0)1.0 (1.0 to 1.0)1.5 (1.0 to 2.1)
Cycle 2 Day 12.0 (1.0 to 4.0)2.0 (2.0 to 2.0)1.5 (1.0 to 2.1)2.1 (1.5 to 4.0)1.5 (1.0 to 2.0)1.0 (1.0 to 1.0)
SecondaryPharmacokinetic Profile of INC280 - T1/2

Plasma concentration profile of INC280 in combination with Buparlisib. T1/2 is the terminal half life

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · hr
Pharmacokinetic Profile of INC280 - T1/2
hr200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 1513.4 (4.1 to 31.2)20.8 (16.3 to 28.6)26.0 (13.2 to 28.1)7.3 (7.3 to 7.3)13.1 (7.0 to 19.3)8.0 (4.2 to 28.0)
Cycle 2 Day 19.9 (3.8 to 20.1)17.4 (17.4 to 17.4)26.3 (23.5 to 29.1)8.7 (5.8 to 11.5)6.3 (6.3 to 6.3)4.3 (4.3 to 4.3)
SecondaryPharmacokinetic Profile of Buparlisib - AUCtau

Plasma concentration profile of Buparlisib in combination with INC280. AUCtau is the AUC from time zero to the end of dosing interval.

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · hr*ng/ml
Pharmacokinetic Profile of Buparlisib - AUCtau
hr*ng/ml200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 13072.0 ± 1257.871865.0 ± 2291.803328.2 ± 2604.723825.8 ± 2702.564425.3 ± 2702.473658.8 ± 5627.79
Cycle 1 Day 158728.5 (4874.3 to 10962.7)4591.9 (3167.1 to 10562.3)6108.4 (5300.5 to 7605.5)10844.6 (6761.7 to 14927.4)10366.5 (8257.8 to 11052.6)8535.1 (4102.2 to 8908.3)
Cycle 2 Day 17930.8 (3563.5 to 9712.2)3776.7 (3477.6 to 4075.7)6976.0 (3436.1 to 10515.9)5903.0 (4850.4 to 12072.9)7857.2 (7757.7 to 9361.9)7344.3 (7344.3 to 7344.3)
SecondaryPharmacokinetic Profile of Buparlisib - Cmax

Plasma concentration profile of INC280 in combination with Buparlisib. Cmax is the Maximum (peak) observed drug concentration after dose administration.

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · ng/ml
Pharmacokinetic Profile of Buparlisib - Cmax
ng/ml200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 1484.0 ± 509.47351.0 ± 481.70399.0 ± 898.05522.0 ± 1081.12508.0 ± 778.91475.0 ± 1499.76
Cycle 1 Day 15664.0 (568.0 to 791.0)459.0 (294.0 to 623.0)542.0 (456.0 to 791.0)785.0 (684.0 to 886.0)814.0 (628.0 to 1330.0)788.5 (390.0 to 1700.0)
Cycle 2 Day 1560.0 (290.0 to 813.0)377.5 (285.0 to 470.0)611.0 (409.0 to 813.0)529.5 (383.0 to 865.0)735.0 (558.0 to 890.0)600.0 (600.0 to 600.0)
SecondaryPharmacokinetic Profile of Buparlisib - Tmax

Plasma concentration profile of INC280 in combination with Buparlisib. Tmax is the time to reach maximum (peak) observed concentration (Cmax) after dose administration

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · hr
Pharmacokinetic Profile of Buparlisib - Tmax
hr200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 11.0 ± 509.471.0 ± 481.701.0 ± 898.050.6 ± 1081.121.2 ± 778.911.0 ± 1499.76
Cycle 1 Day 150.9 (0.9 to 1.0)2.0 (1.0 to 2.1)1.0 (1.0 to 2.0)1.6 (1.2 to 2.0)1.0 (0.5 to 1.0)1.3 (0.5 to 2.1)
Cycle 2 Day 11.0 (0.5 to 2.0)1.5 (1.0 to 2.0)1.0 (1.0 to 1.0)1.8 (1.0 to 2.1)1.0 (1.0 to 1.0)1.0 (1.0 to 1.0)
SecondaryPharmacokinetic Profile of Buparlisib - T1/2

Plasma concentration profile of INC280 in combination with Buparlisib. T1/2 is the terminal half life

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Reported as:
Median · hr
Pharmacokinetic Profile of Buparlisib - T1/2
hr200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD
Cycle 1 Day 1537.3 (29.1 to 52.4)31.1 (18.7 to 46.4)21.8 (20.8 to 29.4)30.9 (19.9 to 41.8)38.0 (21.3 to 44.9)22.8 (5.8 to 31.5)
Cycle 2 Day 134.0 (10.4 to 37.9)21.3 (16.4 to 26.1)27.0 (9.6 to 44.3)17.2 (16.8 to 31.9)20.1 (19.4 to 41.2)12.0 (12.0 to 12.0)
SecondaryBest Overall Response (BOR)

Best Overall Response (BOR) observed in the study population of INC280 Single Agent and in Combination with Buparlisib. Responses will be assessed by the investigators following the RANO criteria with MRI or CT scans scheduled every 8 weeks. Summary of the RANO response criteria: CR has no T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; PR has ≥50% decrease T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; SD has ≥50% decrease but \<25% increase T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; PD has ≥25% increase in T1-Gd+ (enhancing lesion), increase T2/FLAIR (non-enhancing lesion), presence of new lesion, deterioration in clinical status.

Time frame:
throughout the duration of the trial - approximately 3 years (from FPFV to LPLV)
Reported as:
Number · Participants
Best Overall Response (BOR)
Participants200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab+80 mg QD400 mg BID Tab
Complete Response (CR)0000000
Partial Response (PR)0000000
Stable Disease (SD)0001003
Progressive Disease (PD)5544746
Unknown (UNK)0000000
Not Assessed0101011
SecondaryOverall Survival (OS)

Survival rate of patients from start of treatment to date of death due to any cause. Patients did not reach the milestone for the survival data analysis (terminated early); as such no analysis was done.

Time frame:
throughout the duration of the trial - approximately 3 years (FPFV to LPLV)

No measurements were reported for this outcome.

Adverse events

Collected over Treatment Emergent Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 3 years.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
INC280 200 mg BID Tab—1/1 (100%)0/1 (0%)
200 mg BID Cap+50 mg QD—3/5 (60%)5/5 (100%)
400 mg BID Cap + 50 mg QD—2/6 (33.3%)6/6 (100%)
500 mg BID Cap+50 mg QD—3/4 (75%)4/4 (100%)
500 mg BID Cap+80 mg QD—3/6 (50%)6/6 (100%)
300 mg BID Tab+ 80 mg QD—3/7 (42.9%)7/7 (100%)
400 mg BID Tab+80 mg QD—4/5 (80%)5/5 (100%)
All Patients (Phase Ib)—18/33 (54.5%)33/33 (100%)
400 mg BID Tab—2/9 (22.2%)9/9 (100%)
All Patients (Phase II)—3/10 (30%)9/10 (90%)
Most frequent serious events
Showing 10 of 30
Most frequent serious events
EventINC280 200 mg BID Tab200 mg BID Cap+50 mg QD400 mg BID Cap + 50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab+ 80 mg QD400 mg BID Tab+80 mg QDAll Patients (Phase Ib)400 mg BID TabAll Patients (Phase II)
BRAIN OEDEMANervous system disorders1/10/50/60/40/60/70/50/330/91/10
ALANINE AMINOTRANSFERASE INCREASEDInvestigations0/10/50/60/40/61/73/54/330/90/10
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations0/10/50/60/40/60/73/53/330/90/10
SEIZURENervous system disorders0/10/50/62/41/60/70/53/330/90/10
HAEMORRHAGE INTRACRANIALNervous system disorders0/12/50/60/41/60/70/53/330/90/10
FEBRILE INFECTIONInfections and infestations0/10/50/61/40/60/70/51/330/90/10
APATHYPsychiatric disorders0/10/50/61/40/60/70/51/330/90/10
PNEUMOCYSTIS JIROVECII PNEUMONIAInfections and infestations0/10/50/60/40/60/71/51/330/90/10
FALLInjury, poisoning and procedural complications0/11/50/60/40/60/70/51/330/90/10
APHASIANervous system disorders0/11/50/60/40/60/70/51/330/90/10
Most frequent other events
Showing 10 of 141
Most frequent other events
EventINC280 200 mg BID Tab200 mg BID Cap+50 mg QD400 mg BID Cap + 50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab+ 80 mg QD400 mg BID Tab+80 mg QDAll Patients (Phase Ib)400 mg BID TabAll Patients (Phase II)
ALANINE AMINOTRANSFERASE INCREASEDInvestigations0/11/51/61/40/62/74/59/330/90/10
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations0/11/51/61/40/62/73/58/330/90/10
FATIGUEGeneral disorders0/12/53/61/42/62/72/512/333/93/10
BLOOD BILIRUBIN INCREASEDInvestigations0/11/50/62/40/61/71/55/331/91/10
HYPERGLYCAEMIAMetabolism and nutrition disorders0/12/50/62/41/62/70/57/331/91/10
HEMIPARESISNervous system disorders0/10/50/62/41/61/71/55/331/91/10
HEADACHENervous system disorders0/12/50/61/42/62/72/59/334/94/10
NAUSEAGastrointestinal disorders0/11/52/61/41/63/72/510/332/92/10
DEPRESSIONPsychiatric disorders0/12/50/61/40/63/72/58/331/91/10
CONSTIPATIONGastrointestinal disorders0/12/51/61/40/60/71/55/333/93/10

Baseline characteristics

Full Analysis Set (FAS): The FAS comprised all patients who received at least one full or partial dose of study treatment. Patients were classified according to the planned treatment.

Age, Categorical
Age, Categorical(Participants)200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab +80 mg QD400 mg BID TabTotal
<=18 years00000000
Between 18 and 65 years2645441035
>=65 years30013108
Sex: Female, Male
Sex: Female, Male(Participants)200 mg BID Cap+50 mg QD400 mg BID Cap+50 mg QD500 mg BID Cap+50 mg QD500 mg BID Cap+80 mg QD300 mg BID Tab +80 mg QD400 mg BID Tab +80 mg QD400 mg BID TabTotal
Female022302716
Male542373327
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Study locations

13 sites
  • Dana Farber Cancer Institute SC
    Boston, Massachusetts 02215, United States
  • Columbia University Medical Center- New York Presbyterian Dept of Oncology
    New York, New York 10032, United States
  • Memorial Sloan Kettering Cancer Center Neurology
    New York, New York 90033, United States
  • Duke University Medical Center Duke - Baker
    Durham, North Carolina 27710, United States
  • University of Texas MD Anderson Cancer Center SC-3
    Houston, Texas 77030, United States
  • Novartis Investigative Site
    Bonn, 53105, Germany
  • Novartis Investigative Site
    Heidelberg, 69120, Germany
  • Novartis Investigative Site
    Tübingen, 72076, Germany
  • ErasmusMC Cancer Institute - Neurooncology, RM G3-55
    Rotterdam, 3075EA, Netherlands
  • University Medical Center Utrecht, Rm Q05.4.300, P.O. Box 85500
    Utrecht, 3508 GA, Netherlands
  • Novartis Investigative Site
    Barcelona, Catalunya 08035, Spain
  • Novartis Investigative Site
    Madrid, 28041, Spain
  • Novartis Investigative Site
    St. Gallen, 9007, Switzerland
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References and documents

Publications

  • van den Bent M, Azaro A, De Vos F, Sepulveda J, Yung WKA, Wen PY, Lassman AB, Joerger M, Tabatabai G, Rodon J, Tiedt R, Zhao S, Kirsilae T, Cheng Y, Vicente S, Balbin OA, Zhang H, Wick W. A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma. J Neurooncol. 2020 Jan;146(1):79-89. doi: 10.1007/s11060-019-03337-2. Epub 2019 Nov 27. PubMed 31776899 ↗

Individual participant data

Plan to share: Undecided — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 30, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01870726
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Jun 6, 2013
Start date
Jan 9, 2014
Primary completion
Dec 23, 2016
Completion
Dec 23, 2016
Results posted
May 24, 2018
Last update
May 30, 2018

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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