Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
XL184 · 6 trials · 13 indications
The duration of Progression-Free Survival (PFS) using progression events as determined by Independent Review Committee (IRC) per mRECIST, or death due to any cause. The analysis was conducted after at least 315 subjects were randomized and at least 138 events were observed.
Response and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features
To evaluate the effect of multiple daily doses of XL184 on single dose PK of rosiglitazone
Treatment duration was defined as the number of days from the first dose to the last dose (measured in weeks), including any days of treatment interruption that occurred before the last dose of study drug.
Objective Response Rate is defined as the number of participants for whom the best overall response is complete (CR) or partial response (PR) confirmed by repeat assessments no less than four weeks after the criteria for the initial response were first met.
| Arm | Type | Description |
|---|---|---|
| 1 | EXPERIMENTAL | - |
| 2 | PLACEBO_COMPARATOR | - |
| Group A cabozantinib 175 mg | EXPERIMENTAL | cabozantinib, 175 mg, taken orally once per day (qd). |
| Group B cabozantinib 125 mg | EXPERIMENTAL | cabozantinib, 125 mg, taken orally once per day (qd). |
| Group C 125 mg | EXPERIMENTAL | cabozantinib, 125 mg, taken orally once per day (qd). |
| All subjects | EXPERIMENTAL | All subjects will receive daily XL184, and two single doses of rosiglitazone, 3 weeks apart |
| Arm 1 | EXPERIMENTAL | XL184 will be initiated at the start of the 6-7 week concurrent phase of RT (+TMZ; some subjects found to have specific gene activity in their tumor tissue may not receive TMZ), given as a single agent during the rest phase (4 weeks), if applicable, and continued subsequently in the maintenance phase. |
| Arm 2 | EXPERIMENTAL | XL184 will be initiated during the maintenance phase with TMZ |
| MTD Expansion | EXPERIMENTAL | XL184 will be initiated at the start of the 6-7 week concurrent phase of RT (+TMZ; some subjects found to have specific gene activity in their tumor tissue may not receive TMZ), given as a single agent in the rest phase (4 weeks), if applicable, and continued subsequently in the maintenance phase. Subjects in this group will receive XL184 and TMZ at the maximally tolerated dose levels determined in Arms 1 and 2. |
| Phase 1 Arm | EXPERIMENTAL | Escalating doses of XL184 + erlotinib |
| Phase 2 Arm 1 | EXPERIMENTAL | XL184 + erlotinib (dose determined from Phase 1 portion of study) |
| Phase 2 Arm 2 | EXPERIMENTAL | XL184 administered as a single agent |
| Name | Type | Description |
|---|---|---|
| XL184 | DRUG | Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily |
| Placebo | DRUG | Gelatin capsules color and size-matched to XL184 capsules administered orally daily |
| rosiglitazone | DRUG | one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later |
| temozolomide | DRUG | TMZ will be supplied as 5-, 20-, 100-, 250-, 140-, and 180-mg capsules. The starting dose will be 75 mg/m2/day given daily with concurrent RT for 6 weeks |
| Radiation Therapy | RADIATION | Subjects will receive RT consisting of fractionated focal irradiation administered using 1.8-2 Gy/fraction, daily for 5 days/week for 6-7 weeks, for a total dose of up to 60 Gy. |
| erlotinib | DRUG | Tablets administered orally daily. |
Inclusion Criteria: * The subject has a histologically confirmed diagnosis of MTC that cannot be removed by surgery, is locally advanced, or has spread in the body. * The subject is at least 18 years old. * The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2. * The s...
XL184 is an investigational small molecule being studied in oncology. Clinical trials have evaluated it in advanced malignancies including lymphoma, thyroid carcinoma, glioblastoma multiforme, and papillary thyroid cancer. It has also been studied in combination with temozolomide and radiation therapy for the initial treatment of glioblastoma.
XL184 is being developed by Exelixis, Inc., a biopharmaceutical company traded on NASDAQ under the ticker EXEL. The drug is an investigational small molecule in the oncology therapeutic area.
XL184 has completed clinical trials in Phase 1 and Phase 2. It remains an investigational drug and is not approved by the FDA. The completed trials include a Phase 1 study in advanced malignancies and a Phase 2 study in glioblastoma multiforme.
XL184 has been studied in several completed trials. NCT00215605 was a Phase 1 study in adults with advanced malignancies. NCT00704288 was a Phase 2 study in glioblastoma multiforme. NCT00960492 was a Phase 1 study combining XL184 with temozolomide and radiation in glioblastoma. NCT01100619 was a drug-drug interaction study in solid tumors.
Yes, XL184 is also known as cabozantinib. Clinical trial titles refer to XL184 (Cabozantinib), confirming that the two names refer to the same drug. The drug has been evaluated under both names in oncology studies.
XL184 has been studied in several cancer types. These include lymphoma, thyroid carcinoma, papillary thyroid cancer, follicular thyroid cancer, Huerthle cell thyroid cancer, renal cell carcinoma, glioblastoma multiforme, giant cell glioblastoma, and gliosarcoma. All trials were conducted in the United States.