Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Capmatinib
INC280 · 12 trials · 11 indications
This is a master screening entry with sub-study entries to capture the results of each arm. As such a primary outcome measure for this entry is not relevant, however this entry will be used to report the number of patients with a cancer containing the appropriate genetic alteration that have been successfully allocated and consented to each arm.
Tumor response was assessed by a blinded independent review committee (BIRC) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. The primary efficacy endpoint ORR was estimated and the exact 95% confidence interval (CI) was provided by cohort.
A DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Percentage of participants with AEs, including changes from baseline in vital signs and laboratory results qualifying and reported as AEs. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: Death
Percentage of participants with at least one dose reduction. Dose reductions were only allowed for capmatinib
Percentage of participants with at least one dose interruption. Dose interruptions were allowed for capmatinib and spartalizumab.
The relative dose intensity of capmatinib and spartalizumab is computed as the ratio of dose intensity and planned dose intensity, multiplied by 100.
OS is defined as the time from date of start of treatment to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive. Results are not available because randomized part never started.
Collection of adverse events and serious adverse events at every visit. Safety assessment will be performed and include local laboratory test monitoring in addition to local standard of care assessments.
Percentage of participants with a best overall response defined as confirmed complete response (CR) or partial response (PR) by BIRC assessment per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Overall response rate is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), as per RECIST 1.1 (Overall Response (OR) = CR + PR). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
midazolam and caffeine pharmacokinetic parameters
midazolam and caffeine pharmacokinetic parameter
midazolam and caffeine pharmacokinetic parameter
midazolam and caffeine pharmacokinetic parameter
midazolam and caffeine pharmacokinetic parameter
midazolam and caffeine pharmacokinetic parameter
midazolam and caffeine pharmacokinetic parameter
midazolam and caffeine pharmacokinetic parameter
digoxin and rosuvastatin pharmacokinetics parameters
digoxin and rosuvastatin pharmacokinetics parameters
digoxin and rosuvastatin pharmacokinetics parameters
digoxin and rosuvastatin pharmacokinetics parameters
digoxin and rosuvastatin pharmacokinetics parameters
digoxin and rosuvastatin pharmacokinetics parameters
digoxin and rosuvastatin pharmacokinetics parameters
digoxin and rosuvastatin pharmacokinetics parameters
INC280 pharmacokinetic parameters
INC280 pharmacokinetic parameters
INC280 pharmacokinetic parameters
INC280 pharmacokinetic parameters
INC280 pharmacokinetic parameters
INC280 pharmacokinetic parameters
INC280 pharmacokinetic parameters
Incidence and frequency of DLT during the first cycle of INC280 treatment in the dose escalation part according to the CTCAE.
| Arm | Type | Description |
|---|---|---|
| Treatment Arm 1: Alectinib | EXPERIMENTAL | This alectinib treatment arm is for adult, paediatric and TYA patients with ALK-positive cancers. |
| Treatment Arm 2: Atezolizumab | EXPERIMENTAL | This atezolizumab treatment arm is for adult, paediatric and TYA patients with cancers with high tumour mutational burden (TMB) or microsatellite instability high (MSI-high) or proven (previously diagnosed) constitutional mismatch repair deficiency (CMMRD). |
| Treatment Arm 3: Entrectinib | EXPERIMENTAL | This entrectinib treatment arm is for adult, paediatric and TYA patients with ROS1 gene fusion-positive cancers. |
| Treatment Arm 4: Trastuzumab in combination with pertuzumab | EXPERIMENTAL | This trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations. |
| Treatment Arm 5: Vemurafenib in combination with cobimetinib | EXPERIMENTAL | This vemurafenib and cobimetinib treatment arm is for BRAF V600 mutation-positive cancers occurring in adults only. |
| Treatment Arm 6: Capmatinib | EXPERIMENTAL | This capmatinib treatment arm is for adult patients with cancers harbouring MET dysregulations. |
| Cohort 1 | EXPERIMENTAL | Treatment Naive participants |
| Cohort 2 | EXPERIMENTAL | Participants received one or two prior lines of treatment |
| Run-in part: capmatinib + spartalizumab | EXPERIMENTAL | Participants (enrolled in the run-in part) were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days |
| Randomized part: capmatinib+spartalizumab | EXPERIMENTAL | Participants (enrolled in the randomized part) treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days |
| Randomized part: docetaxel | ACTIVE_COMPARATOR | Participants (enrolled in the randomized part) treated with docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days |
| Capmatinib | EXPERIMENTAL | Starting dose of study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted. |
| Capmatinib + Nazartinib | EXPERIMENTAL | Starting dose of the study treatment for patients should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted. |
| Capmatinib + Gefitinib | EXPERIMENTAL | Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted. |
| Capmatinib + Osimertinib | EXPERIMENTAL | Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted. |
| Cohort 1a: Pre-treated patients with MET GCN ≥ 10 (2/3L) | EXPERIMENTAL | Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L) |
| Cohort 1b:Pre-treated patients with MET GCN ≥ 6 and < 10 (2/3L) | EXPERIMENTAL | Pre-treated patients with MET GCN ≥ 6 and \< 10 treated with INC280 at 400 mg BID as second or third line (2/3L) |
| Cohort 2: Pre-treated patients with MET GCN ≥ 4 and < 6 (2/3L) | EXPERIMENTAL | Pre-treated patients with MET GCN ≥ 4 and \< 6 treated with INC280 at 400mg BID as second or third line (2/3L) |
| Cohort 3: Pre-treated patients with MET GCN < 4 (2/3L) | EXPERIMENTAL | Pre-treated patients with MET GCN \< 4 treated with INC280 at 400mg BID as second or third line (2/3L) |
| Cohort 4: Pre-treated patients with MET mutation regardless of MET GCN (2/3L) | EXPERIMENTAL | Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L) |
| Cohort 5a: Treatment-naïve patients with MET GCN ≥10 (1L) | EXPERIMENTAL | Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L) |
| Cohort 5b: Treatment-naïve patients with MET mutation regardless of MET GCN (1L) | EXPERIMENTAL | Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) |
| Cohort 6.1 (expansion of Cohort 1a): Pre-treated patients MET GCN ≥ 10 without MET mutation (2L) | EXPERIMENTAL | Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a) |
| Cohort 6.2 (expansion of Cohort 4): Pre-treated patients with MET mutation (2L) | EXPERIMENTAL | Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4) |
| Cohort 7 (expansion of Cohort 5b): Treatment-naïve with MET mutation regardless of MET GCN (1L) | EXPERIMENTAL | Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b) |
| INC280 100 mg Cap QD Phase Ib | EXPERIMENTAL | cap=capsule; QD=once daily |
| INC280 200 mg Cap QD Phase Ib | EXPERIMENTAL | cap=capsule; QD=once daily |
| INC280 400 mg Cap QD Phase Ib | EXPERIMENTAL | cap=capsule; QD=once daily |
| INC280 800 mg Cap QD Phase Ib | EXPERIMENTAL | cap=capsule; QD=once daily |
| INC280 200 mg Cap BID Phase Ib | EXPERIMENTAL | cap=capsule; BID=twice daily |
| INC280 400 mg Cap BID Phase Ib | EXPERIMENTAL | cap=capsule; BID=twice daily |
| INC280 600 mg Cap BID Phase Ib | EXPERIMENTAL | cap=capsule; BID=twice daily |
| INC280 200 mg Tab BID Phase Ib | EXPERIMENTAL | tab=tablet; BID=twice daily |
| INC280 400 mg Tab BID Phase Ib | EXPERIMENTAL | tab=tablet; BID=twice daily |
| INC280 400 mg Cap BID Phase II | EXPERIMENTAL | cap=capsule; BID=twice daily |
| INC280 400 mg Tab BID Phase II | EXPERIMENTAL | tab=tablet; BID=twice daily |
| INC280 | EXPERIMENTAL | - |
| Normal hepatic function | EXPERIMENTAL | Subjects with normal hepatic function |
| Mild hepatic impairment | EXPERIMENTAL | Subjects with mild hepatic impairment |
| Moderate hepatic impairment | EXPERIMENTAL | Subjects with moderate hepatic impairment |
| Severe hepatic impairment | EXPERIMENTAL | Subjects with severe hepatic impairment |
| Name | Type | Description |
|---|---|---|
| Alectinib | DRUG | Adult patients will be administered alectinib orally at a dose of 600 mg (four 150 mg capsules) twice daily. Paediatric patients with a body weight ≥40 kg and who are able to swallow the capsules will be administered alectinib orally at a dose of 600 mg (four 150 mg capsules) twice daily. Each cycle of treatment will consist of 28 days and patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent. |
| Atezolizumab | DRUG | Adult patients will receive 1200 mg of atezolizumab intravenously every 21 days. Paediatric patients will receive atezolizumab at a dose of 15 mg/kg (maximum 1200 mg) every 21 days. Patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent. |
| Entrectinib | DRUG | Adult and paediatric patients with body surface area (BSA) ≥1.51 m\^2 will receive entrectinib orally at a dose of 600 mg daily dose (three 200 mg capsules per day). Paediatric patients with BSA \<1.51 m\^2 will receive a dose adjusted for BSA. Each cycle of treatment will consist of 28 days and patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent. |
| Trastuzumab in combination with pertuzumab | DRUG | The initial loading dose of trastuzumab is 8 mg/kg body weight followed thereafter by a maintenance dose of 6 mg/kg body weight administered intravenously every 21 days. The initial loading dose of pertuzumab is 840 mg followed thereafter by a maintenance dose of 420 mg administered intravenously every 21 days. Paediatric patients will receive a dose of pertuzumab adjusted by body weight. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent. |
| Vemurafenib in combination with cobimetinib | DRUG | Patients will receive vemurafenib at a dose of 960 mg (four tablets of 240 mg) orally on a twice daily schedule throughout a 28-day cycle. Patients will receive cobimetinib at a dose of 60 mg (three tablets of 20 mg) to be taken orally, once daily for 21 consecutive days (days 1 to 21 in each 28-day cycle); followed by a 7-day break. Patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent. |
| Capmatinib | DRUG | Patients will be administered capmatinib orally at a daily dose of 800 mg consisting of 400 mg (two 200 mg tablets) twice daily. Each cycle of treatment will consist of 28 days and patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent. |
| Spartalizumab | DRUG | Spartalizumab 400 mg via intravenous infusion once every 28 days |
| Docetaxel | DRUG | Docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days |
| Nazartinib | DRUG | Capsule for oral use; 25 mg, 50 mg; once a day |
| Gefitinib | DRUG | tablets for oral use; 250mg; once a day |
| Osimertinib | DRUG | Tablets for oral use; 40 mg, 80 mg; once a day. |
| INC280 | DRUG | During Phase Ib, INC280 was taken at escalating doses. During Phase II part, INC280 was taken at recommended Phase II dose. |
| Midazolam | DRUG | - |
| Caffeine | DRUG | - |
| digoxin | DRUG | - |
| rosuvastatin | DRUG | - |
THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA OUTLINED BELOW AND WITHIN THE SPECIFIC TREATMENT ARM APPENDIX TO WHICH THEY ARE ENROLLED. Core Inclusion Criteria: 1. Any patient (adult patients or children and TYA as defined in each treatment arm appendix) with histologically proven locally advan...
INC280 is an investigational small molecule developed by Novartis AG (ticker NVS) for oncology indications. It is being studied in advanced solid tumors, non-small cell lung cancer, and haematological malignancies. INC280 is also known as capmatinib.
INC280 targets MET, a receptor tyrosine kinase. It acts as an inhibitor of MET, which is involved in cell growth and survival. This makes it relevant for cancers with MET alterations, such as MET exon 14 skipping mutations in non-small cell lung cancer.
INC280 is being developed by Novartis AG, which trades under the ticker NVS. Novartis sponsors the clinical trials evaluating INC280 in various cancer types.
INC280 is in Phase 1 development according to its overall program status. However, individual trials listed are Phase 2, including NCT05722886, NCT04677595, NCT03647488, and NCT03040973. It is investigational and not approved.
INC280 has been studied in several clinical trials, including NCT05722886 (DETERMINE master screening protocol, recruiting), NCT04677595 (completed in Chinese NSCLC patients), NCT03647488 (completed combination study), and NCT03040973 (active, not recruiting). These trials cover solid tumors and haematological malignancies.
Yes, INC280 is the same as capmatinib. Capmatinib is the international nonproprietary name for the drug, while INC280 is a code name used during development. Both refer to the same MET inhibitor developed by Novartis.