Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ceritinib (LDK378)
ceritinib · 8 trials · 10 indications
PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression (as assessed by BIRC per RECIST 1.1) or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or had received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. The distribution of PFS was estimated using the Kaplan-Meier (KM) method.
PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.
Overall response rate (ORR) is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (\< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.
ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 as assessed by investigator
Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.
Graded according to NCI CTCAE v4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.
Graded according to NCI CTCAE v4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.
A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 21 days of treatment with LDK378 and meets a specified defined criteria. A participant with multiple occurrences of DLTs under one treatment is counted only once in the Adverse Event category for that treatment. A participant with multiple DLTs within a primary system organ class is counted only once in the total row.
| Arm | Type | Description |
|---|---|---|
| Ceritinib | EXPERIMENTAL | Ceritinib administered continuously through oral dosing at a dosage of 750 mg once daily in fasted state. |
| Chemotherapy | ACTIVE_COMPARATOR | Pemetrexed plus cisplatin or carboplatin (based on Investigator's choice) for 4 cycles (Induction) followed by pemetrexed as single agent (Maintenance) |
| Arm 1 (PrALKi=Y, PrBRad=Y) | EXPERIMENTAL | Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation). |
| Arm 2 (PrALKi=Y, PrBRad=N) | EXPERIMENTAL | Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation). |
| Arm 3 (PrALKi=N, PrBRad=Y) | EXPERIMENTAL | Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation). |
| Arm 4 (PrALKi=N, PrBRad=N) | EXPERIMENTAL | Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation). |
| Arm 5 (LepDis) | EXPERIMENTAL | Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3. |
| Dose Escalation | EXPERIMENTAL | - |
| Dose Expansion | EXPERIMENTAL | - |
| ceritinib 450 mg with a low-fat meal | EXPERIMENTAL | Oral ceritinib QD (21 days/ cycle) at a dose of 450 mg (3×150 mg/capsule) administered in the morning immediately (within 30 minutes)following a low-fat meal. |
| ceritinib 600 mg with a low-fat meal | EXPERIMENTAL | Oral ceritinib QD (21 days/ cycle) at a dose of 600 mg (4×150 mg/capsule) administered in the morning immediately (within 30 minutes) following a low-fat meal. |
| ceritinib 750 mg on an empty stomach | ACTIVE_COMPARATOR | Oral ceritinib QD (21 days/ cycle) at a dose of 750 mg (5×150 mg/capsule) administered in the morning on an empty stomach (i.e., fasted from food and drink except water) |
| Arm 1 (ceritinib MTD then with gemcitabine alone) | EXPERIMENTAL | Dose Escalation Cohort 1: Patients with advanced solid tumors for whom gemcitabine hydrochloride-based therapy is clinically appropriate receive ceritinib PO (QD on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Expansion Cohort 1E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors who previously progressed on gemcitabine hydrochloride-based therapy receive ceritinib and gemcitabine hydrochloride as in the dose escalation cohort 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel) | EXPERIMENTAL | Dose Escalation Cohort 2: Patients with advanced pancreatic cancer receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Expansion Cohort 2E: Once the MTD of ceritinib has been determined, patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation as in the dose escalation cohort 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm 3 (ceritinib MTD then with gemcitabine and cisplatin) | EXPERIMENTAL | Dose Escalation Cohort 3: Patients with advanced solid tumors for whom gemcitabine hydrochloride and cisplatin-based therapy is clinically appropriate receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Expansion Cohort 3E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and cisplatin as in the dose escalation cohort 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
| LDK378 | EXPERIMENTAL | All participants were administered a single-agent LDK378 (Ceritinib) orally, once daily, continuously in fasted or fed conditions. |
| Name | Type | Description |
|---|---|---|
| Ceritinib | DRUG | Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. |
| Pemetrexed | DRUG | Pemetrexed was administered at a dose of 500 mg/m\^2 as an intravenous (iv) infusion on Day 1 of each 21-day cycle |
| Cisplatin | DRUG | Cisplatin was administered by iv infusion at a dose of 75 mg/m\^2 every 21 days for up to 4 cycles. |
| Carboplatin | DRUG | Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles |
| Docetaxel | DRUG | Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m\^2 every 21 days. |
| warfarin | DRUG | - |
| midazolam | DRUG | - |
| Ceritinib (LDK378) | DRUG | - |
| Nivolumab | DRUG | - |
| Gemcitabine Hydrochloride | DRUG | Given IV |
| Laboratory Biomarker Analysis | OTHER | Correlative studies |
| Paclitaxel Albumin-Stabilized Nanoparticle Formulation | DRUG | Given IV |
| Pharmacological Study | OTHER | Correlative studies |
Key Inclusion Criteria: 1. The patient had a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that was Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test was performed at Novartis desig...
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Ceritinib is an investigational small molecule being studied for advanced malignant solid neoplasms, ALK-positive non-small cell lung cancer, ALK-activated tumors, and ALK-positive advanced tumors. It is in Phase 1 clinical development for these oncology indications.
Ceritinib is a kinase inhibitor, as indicated by its -tinib suffix. It is being studied in ALK-positive tumors, suggesting it targets ALK. The drug is in clinical development for ALK-positive non-small cell lung cancer and other ALK-activated tumors.
Ceritinib is being developed by Novartis AG, which trades under the ticker NVS. The company is conducting clinical trials of this investigational drug for ALK-positive non-small cell lung cancer and other oncology indications.
Ceritinib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. It is being studied in trials for ALK-positive non-small cell lung cancer and other advanced solid tumors.
Ceritinib has been studied in several trials, including NCT01828099, a Phase 3 study comparing it to chemotherapy in previously untreated ALK-rearranged NSCLC patients, and NCT01828112, another Phase 3 trial in ALK-positive patients previously treated with chemotherapy and crizotinib. A Phase 1 trial, NCT02299505, examined lower doses with food versus 750 mg fasting.
Yes, Ceritinib is also known as LDK378. Clinical trials often refer to the drug by this alternative name, such as in the Phase 3 studies NCT01828099 and NCT01828112, which are titled with LDK378.