Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication CABOMETYX is a kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma (RCC). ( 1.1 ) patients with advanced renal cell carcinoma, as a first-line treatment in combination with nivolumab ( 1.1 ) patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib ( 1.2 ) adult and pediatric patients 12 years of age and older with locally advanced or… FDA label
Also known as Cabozantinib tablets, Cabozantinib, Cabometyx®, cabozantinib capsules, Cometriq, BMS907351, Cabozantinib S-malate
XL184 · 44 trials · 112 indications
Duration of PFS was defined as the time from randomization to the earlier of either the date of radiographic progression (defined as progressive disease \[PD\] per RECIST 1.1) per BIRC or the date of death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions, with an absolute increase of ≥ 5 mm, unequivocal progression of non-target lesions and/or the appearance of new lesions.
Duration of OS was defined as the time from randomization to death due to any cause. For participants, who were not known to have died at the time of data cutoff and were permanently lost to follow-up, duration of OS was censored at the earlier of the following dates: date the participant was last known to be alive or date of full withdrawal of consent (including survival follow-up), or date of data cutoff. OS was calculated as earlier of date of death or censoring - date of randomization + 1)/30.4375
OS was defined as the time from randomization to death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.
Duration of PFS was defined as the time from randomization to the earlier of either the date of radiographic progression per BIRC or the date of death due to any cause. PFS (months) = (earliest date of progression, death, censoring - date of randomization + 1)/30.4375. PFS was determined as per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1.
Time to the earlier of either radiographic progressive disease (PD) or death from any cause.
Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).
PFS was defined as the time from randomization to the earlier of either the date of radiographic progression defined as a 20% increase in the sum of the longest diameters of target lesions, or the unequivocal appearance of new lesions, or progression of non-target disease per Blinded Independent Radiology Committee (BIRC) or the date of death due to any cause per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
OS was defined as the time from randomization to death due to any cause.
The primary analysis of PFS is the time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria) or death due to any cause, whichever occurred first. A Kaplan-Meier analysis was performed to estimate the median duration.
ORR is defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR), i.e., two CRs and/or PRs at least 4 weeks apart, according to the RECIST v1.1 criteria. CR=disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Will assess the proportion of subjects with partial response or complete response as defined by Response Evaluation Criteria in Solid Tumors version 1.1 response criteria. ORR will be calculated with 95% confidence interval by binomial distribution. The ability of biomarkers to predict ORR will be estimated by chi-square test and/or logistic regression model.
To evaluate measurable disease overall response. Subjects were evaluated by CT scans at regular intervals for disease assessment by RECISTv1.1 criteria for the duration of treatment. Response Evaluation Criteria in Solid Tumors (RECIST) is a standard measure of how well cancer patients respond to treatment. Possible scores are CR (Complete Response; total disappearance of all target lesions), PR (Partial Response; at least a 30% decrease of the sum of the longest diameter of all target lesions), PD (Progressive Disease; at least a 20% increase of the sum of the longest diameter of all target lesions), and SD (Stable Disease; neither a sufficient decrease for PR, or sufficient increase for PD). Overall response is the count of PR and CR scores among the participants' best RECISTv1.1 responses.
* Response rate = proportion of participants who achieve complete response or partial response * Complete response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Progress-free survival in participants, defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever comes first.
This is defined as the percentage of subjects who are free of progression 6 months after study treatment start. Progression is defined death, radiographic progression or clinical deterioration attributed disease progression as judged by an investigator. Radiographic progression is defined using the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm and/or appearance of new lesions.
Overall response rate (ORR) is defined as the percentage of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
determined by the proportion of complete responses, partial responses, and stable disease for at least 3 months of therapy using RECIST 1.1 while including markers AFP/ beta-hcg.
The central nervous system (CNS) ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria in the evaluation CNS lesions on treatment: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
The PFS rate for nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma using imRECIST.
The percentage of participants with a complete response following treatment. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.
Complete Response (CR) is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.
DCR is defined using the RECIST 1.1 criteria as the proportion of subjects who have achieved confirmed complete response (CR), confirmed partial response (PR) or stable disease (SD) at 16-weeks.
Estimate the pathologic response (PaR) rate to neoadjuvant cabozantinib and atezolizumab in subjects with muscle-invasive urothelial cancer of the bladder. Pathologic response rate (PaR) is defined as the absence of residual muscle-invasive cancer in the surgical specimen (pathologic downstaging to ≤ pT1pN0), which includes pT0, pT1, pTa, and pTis
Objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.0 per investigator The analysis of ORR in the RDT Cohorts were defined as the proportion of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) per mRECIST 1.0 during the 12-week Lead-In Stage. In the NRE Ovarian Cohort, mRECIST 1.1 was used. ORR for the NRE CRPC Cohorts was not a primary objective and is therefore not captured in the table below.
The reduction of bone scan lesion area (BSLA) by \> 30% was used as the quantitative measure of BSR. BSR was a primary outcome measure for only the NRE CRPC Cohorts.
Progression Free Survival during the Randomized Stage (Randomized Population)
The phase I objective of this study is to establish the maximal tolerated dose (MTD) of cabozantinib in 20 mg, 40 mg and 60 mg dose escalation cohorts in combination with Lu-177 dotatate at a standard dose of 7.4 GBq in four (4) 8-week cycles followed by continuation cabozantinib. Due to overlapping toxicities of cabozantinib and Lu-177 dotatate and to allow more incremental dose escalation of cabozantinib, alternating day dosing of 40mg/20mg and 60mg/40mg cohorts are incorporated into the schema. This is expected to reduce the risk of overlapping toxicities while still achieving radio-sensitizing anti-angiogenic, multi-targeted therapy in combination with the beta-emitting radiation from lutetium 177 synergistic due to the prolonged half-life of cabozantinib.
3+3 design to find the maximum tolerated dose (MTD) of cabozantinib when used in combination with 13-cis-retinoic acid
Defined as the highest dose studied for which the observed incidence of dose limiting toxicities (DLT) is less than 33%. Determined per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Defined as the proportion of participants best response to treatment. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Will be assessed by the Common Terminology Criteria for Adverse Events version 5.0.
To determine the maximum tolerated dose (MTD) and recommended dose and schedule for the subsequent Expansion Stage of daily oral administration of cabozantinib in subjects with metastatic castration-resistant prostate cancer (mCRPC) when taken in combination with 177Lu-PSMA-617
To evaluate preliminary efficacy by estimating the progression-free survival (PFS) at 24 weeks (PFS24w) as assessed by per PCWG3-modified RECIST v1.1
To determine the maximum tolerated dose (MTD) and/or recommended dose and schedule for the subsequent Expansion Stage of daily oral administration of cabozantinib in subjects with solid tumors when taken in combination with atezolizumab.
To evaluate preliminary efficacy by estimating the Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1.
To establish the MTD and recommended Phase 2 dose (or dose range as appropriate) of XL184 when administered orally on a once daily schedule in subjects with advanced or metastatic solid tumors.
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 |
|---|---|---|
| Cabozantinib/Zanzalintinib | EXPERIMENTAL | Depending on the study treatment received in the parent study, participants may receive cabozantinib alone or in combination with other agents; zanzalintinib alone or in combination with other agents, or comparator. |
| Experimental Arm | EXPERIMENTAL | Subjects with mCRPC will receive cabozantinib 40mg oral, qd + atezolizumab 1200mg infusion, q3w |
| Control Arm | ACTIVE_COMPARATOR | Subjects with mCRPC will receive active comparator of EITHER abiraterone 1000mg oral, qd + prednisone 5 mg oral, bid; OR enzalutamide 160mg oral, qd as designated by the Investigator prior to randomization |
| Atezolizumab + Cabozantinib | EXPERIMENTAL | Participants received atezolizumab on Day 1 of each 21-day cycle and cabozantinib orally once daily on Days 1-21 of each cycle. |
| Docetaxel | ACTIVE_COMPARATOR | Participants received docetaxel on Day 1 of each 21-day cycle. |
| Cabozantinib | EXPERIMENTAL | cabozantinib (60 mg) once daily orally (qd) |
| Placebo | PLACEBO_COMPARATOR | placebo once daily orally (qd) |
| Single-Agent Cabozantinib arm | OTHER | Participants with advanced HCC will receive cabozantinib 60 mg qd |
| Cabozantinib (XL184) | EXPERIMENTAL | Cabozantinib (XL184) 60 mg tablet once daily |
| Everolimus (Afinitor) | ACTIVE_COMPARATOR | Everolimus (Afinitor) 10 mg tablet once daily. |
| prednisone | ACTIVE_COMPARATOR | Subjects randomized to the prednisone arm will also receive placebo-matched cabozantinib. |
| 1 | EXPERIMENTAL | - |
| 2 | PLACEBO_COMPARATOR | - |
| Arm 1 | EXPERIMENTAL | Patients with non-small cell lung cancer who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations. |
| Arm 2 | EXPERIMENTAL | Patients with urothelial carcinoma who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations. |
| Arm 3 | EXPERIMENTAL | Patients with non-colon gastrointestinal cancers who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations. |
| Arm 4 | EXPERIMENTAL | Patients with upper aerodigestive tract cancers who have failed first line treatment may receive either regorafenib (Stivarga), afatinib (Gilotrif), or cabozantinib (Cabometyx) at the recommended dose level, depending on their specific genomic alterations. |
| Treatment (pembrolizumab, cabozantinib) | EXPERIMENTAL | Patients receive pembrolizumab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
| Cabozantinib and Pembrolizumab, all patients | EXPERIMENTAL | - |
| Cohort A: Cabozantinib | EXPERIMENTAL | Patients randomized to Cohort A will take cabozantinib at a dose of 60 mg by mouth once each day of each 28-day cycle. Treatment may continue indefinitely. At time of progression, patients will continue on cabozantinib daily but will reduce their dose to 40 mg. They will cross over into Cohort B and initiate treatment. |
| Cohort B: Cabozantinib + Nivolumab + Ipilimumab | EXPERIMENTAL | -Patients randomized to Cohort B will take cabozantinib at a dose of 40 mg by mouth once each day. Nivolumab will given IV at a dose of 3 mg/kg over approximately 30 minutes every 3 weeks for 4 doses, followed by 480 mg over approximately 30 minutes every 4 weeks until treatment discontinuation. Ipilimumab will be given IV at a dose of 1 mg/kg over approximately 30 minutes every 3 weeks for 4 doses. Treatment may continue for up to 2 years. |
| Crossover from Cohort A to Cohort B: Cabozantinib + Nivolumab + Ipilimumab | EXPERIMENTAL | -Participants who cross-over from Cohort A into Cohort B will initiate treatment with nivolumab at a dose of 3 mg/kg IV over approximately 30 minutes and ipilimumab at a dose of 1 mg/kg IV over approximately 30 minutes. Nivolumab and ipilimumab will be given every 3 weeks for 4 doses. Nivolumab will then be continued at a dose of 480 mg IV over approximately 30 minutes every 4 weeks, with cabozantinib to continue at 40 mg every day. Treatment may continue for up to 2 years. |
| Cabozantinib and pembrolizumab | EXPERIMENTAL | - |
| Treatment (cabozantinib) | EXPERIMENTAL | Patients receive cabozantinib orally once daily for 12 weeks in the absence of disease progression or unacceptable toxicity. The assigned starting dose for cabozantinib is 60 mg/day. Two dose reduction levels of cabozantinib are permitted |
| Nivolumab + Cabozantinib | EXPERIMENTAL | * Nivolumab was administered every 28 days at a dose of 480mg given intravenously over 30 minutes (+/- 10 minutes) using a volumetric pump with 0.2 to 1.2 micron pore size, low protein binding polyethersulfone membrane in-line filter * Cabozantinib was administered orally, once daily for 28 days at a dose of 40 mg. |
| Nivolumab and Cabozantinib | EXPERIMENTAL | The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Cabozantinib will be administered at a dose of 40mg orally, once daily * Nivolumab will be given at a dose of 240mg every 14 days, intravenously Retreat Phase (Optional) * Participants may elect to stop nivolumab and cabozantinib with confirmed CR after at least 24 weeks of treatment. * Participants who elect to stop and then the condition progresses after stopping study treatment may be eligible to resume nivolumab and cabozantinib therapy. * This resumption will be termed as a retreatment second course phase and is available only while the study remains open and the subject meets specified criteria. |
| Cohort 1 - Cabozantinib, Trastuzumab for HER2+ | EXPERIMENTAL | HER2-positive * Cabozantinib- orally administered daily per treatment cycle, 60 mg per day * Trastuzumab- IV administered once per cycle, 8 mg/kg IV loading dose followed by 6 mg/kg IV Cycle duration equals 3 weeks. Patients are treated indefinitely based on unacceptable toxicity, disease progression, or withdrawal for other reasons. |
| Cohort 2 - Cabozantinib for ER+ and/or PR+ | EXPERIMENTAL | Hormone receptor-positive (ER+ and/or PR+) \- Cabozantinib- orally administered daily per treatment cycle, 60 mg per day Cycle duration equals 3 weeks. Patients are treated indefinitely based on unacceptable toxicity, disease progression, or withdrawal for other reasons. |
| Cohort 3 - Cabozantinib for ER-, PR-, HER2- | EXPERIMENTAL | Triple negative (ER-, PR-, HER2-) \- Cabozantinib- orally administered daily per treatment cycle, 60 mg per day Cycle duration equals 3 weeks. Patients are treated indefinitely based on unacceptable toxicity, disease progression, or withdrawal for other reasons. |
| Single Arm | EXPERIMENTAL | Nivolumab 3mg/kg IV plus Ipilimumab 1mg/kg IV every 3 weeks x 4 cycles with Cabozantinib 40mg PO daily for 12 weeks (Induction); Followed by Maintenance therapy: Nivolumab 480mg IV every 4 weeks for up to 92 weeks; Cabozantinib 40mg PO daily for up to 92 weeks; Maintenance therapy will continue for up to 92 weeks to complete 2 years total of treatment if tolerating therapy well and disease is controlled. |
| Treatment with cabozantinib and nivolumab with nephrectomy | EXPERIMENTAL | All study participants will receive the same study medications, cabozantinib and nivolumab. The study drug, nivolumab, will be administered through an IV infusion every 4 weeks and cabozantinib will be administered orally daily. Initially participants will receive study treatment for 12 weeks. The cabozantinib will then be stopped prior to the nephrectomy. Initially patients enrolled on the study will be assigned to cohort 1. Patients who are assigned to cohort 1 will be treated with cabozantinib until 21 days prior to surgery. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they 1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND 2. have surgical resection of the primary tumor. In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy. |
| Cabozantinib with Ipilimumab/Nivolumab and TACE | EXPERIMENTAL | Subjects receive Cabozantinib 40 mg daily on days 1-28 of a 28 day cycle, this is to be started 7-14 days after the last TACE procedure. Nivolumab 480 mg IV on day 1 of a 28 day cycle (cycle 2 and beyond), this is to be started 7-14 days after the last TACE procedure. Nivolumab: 3mg/kg IV on day 1 of a 21 day cycle x 1 dose. Ipilimumab: 1 mg/kg on day 1 of a 21 day cycle x 1 dose TACE: Within 3-4 weeks of cycle 1 day 1; may be done up to 3 times (9-12 weeks total), the intervals between each TACE treatment can vary based on investigator's discretion |
| Cabozantinib and Atezolizumab | EXPERIMENTAL | Cabozantinib 40mg po daily + Atezolizumab 1200mg iv on day 1; 1 cycle = 21 days |
| Cabozantinib 40 mg orally daily in combination with nivolumab 480 mg IV every 28 days. | EXPERIMENTAL | Cabozantinib is supplied as 20-mg tablets and will be administered orally at a dose of 40 mg/day. Nivolumab is supplied in 100 mg/Vial (10 mg/mL) vials and will be administered IV at a dose of 480 mg every 28 days. |
| Treatment Arm | EXPERIMENTAL | Cabozantinib 40 mg orally daily x 9 weeks plus Atezolizumab 1200 mg every 3 weeks x 3 doses |
| Lead-in Stage - cabozantinib (XL184) | EXPERIMENTAL | Open Label, cabozantinib, 100 mg, po QD for 12 weeks. |
| Randomized Stage - cabozantinib (XL184) | EXPERIMENTAL | Blinded, cabozantinib, 100 mg, po QD until disease progression. |
| Randomized Stage - placebo | PLACEBO_COMPARATOR | Blinded, placebo, 100 mg, po QD until disease progression. |
| Open-Label Extension - cabozantinib (XL184) | EXPERIMENTAL | Open Label, cabozantinib, for subjects that were on placebo during the randomized stage, 100 mg, po QD until disease progression or unacceptable toxicity. |
| Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 100mg | EXPERIMENTAL | Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity. |
| Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 39.4mg | EXPERIMENTAL | Open Label, cabozantinib, 39.4, po QD until disease progression or unacceptable toxicity. |
| A. Non-Randomized Expansion (NRE) Cohort - Ovarian | EXPERIMENTAL | Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity. |
| 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). |
| Cabozantinib and Panitumumab | EXPERIMENTAL | 60 mg Cabozantinib PO daily and 6 mg/kg Panitumumab IV every 2 weeks. |
| Cohort 1 | EXPERIMENTAL | Cabozantinib 20 mg daily with Lu-177 DOTATE administration IV. For cycles 5+, single-agent maintenance of cabozantinib is given at 20 mg qd. |
| Cohort 2 | EXPERIMENTAL | Cabozantinib 40 mg qod alternating with 20 mg qod with Lu-177 DOTATE administration IV. For cycles 5+, single-agent maintenance of cabozantinib is given at 40 mg qd. |
| Cohort 3 | EXPERIMENTAL | Cabozantinib 40 mg qd with Lu-177 DOTATE administration IV. For cycles 5+, single-agent maintenance of cabozantinib is given at 40 mg qd. |
| Cohort 4 | EXPERIMENTAL | Cabozantinib 60 mg qod alternating with 40 mg qod with Lu-177 DOTATE administration IV. For cycles 5+, single-agent maintenance of cabozantinib is given at 60 mg qd. |
| Cohort 5 | EXPERIMENTAL | Cabozantinib 60 mg qd with Lu-177 DOTATE administration IV. For cycles 5+, single-agent maintenance of cabozantinib is given at 60 mg qd until disease progression. |
| Cabozantinib and 13-cis-retinoic acid | EXPERIMENTAL | Cabozantinib will be given orally once every day with cycles repeated every 4 weeks (28 days, +/- 3 days), with no rest periods between cycles, combined with 13-cis-retinoic acid at 80mg/m2/dose twice daily for two consecutive weeks (14 days) out of every four weeks (28 days, +/- 3 days). |
| Cabozantinib plus Durvalumab (Gastric & esophageal cancer cohort) | EXPERIMENTAL | Cabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab \*Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle |
| Cabozantinib plus Durvalumab (Colorectal cancer cohort) | EXPERIMENTAL | Cabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab \*Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle |
| Cabozantinib plus Durvalumab (Hepatocellular carcinoma cohort) | EXPERIMENTAL | Cabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab \*Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle |
| Cabozantinib plus Durvalumab plus Tremelimumab (Hepatocellular carcinoma cohort) | EXPERIMENTAL | Cabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab \*Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle Tremelimumab \*Single dose of 300mg intavenous (IV) infusion on day 1 of cycle 1 |
| Treatment (cabozantinib, enfortumab vedotin) | EXPERIMENTAL | Patients receive cabozantinib PO QD on days 1-28 and enfortumab vedotin IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Dose Escalation (Part 1) | EXPERIMENTAL | Part 1 will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the MTD and/or recommended dose and schedule |
| Dose Expansion Cohort (Part 2) | EXPERIMENTAL | Expansion Phase to assess identified MTD and schedule from Part 1. |
| Dose Escalation | EXPERIMENTAL | Subjects will accrue in cohorts of 3-6 subjects for evaluation of cabozantinib tablet dose of either 20 mg, 40 mg, and 60 mg orally qd in combination with standard dosing regimen of atezolizumab (1200 mg infusion q3w). A standard "3 plus 3" design will be utilized to determine a recommended combination dosing regimen for the Expansion Stage. |
| Expansion Cohort 1 | EXPERIMENTAL | RCC subjects with clear cell histology who have not received prior systemic anticancer therapy. |
| Expansion Cohort 2 | EXPERIMENTAL | UC subjects (including bladder, renal pelvis, ureter, urethra) who have progressed on or after platinum-containing chemotherapy. |
| Expansion Cohort 3 | EXPERIMENTAL | UC subjects (including bladder, renal pelvis, ureter, urethra) who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy. |
| Expansion Cohort 4 | EXPERIMENTAL | UC subjects (including bladder, renal pelvis, ureter, urethra) eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy. |
| Expansion Cohort 5 | EXPERIMENTAL | UC subjects (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune check-point inhibitor (ICI) (anti-PD1 or anti-PD-L1) therapy. |
| Expansion Cohort 6 | EXPERIMENTAL | CRPC subjects who have radiographically progressed in soft tissue on or after enzalutamide and/or abiraterone acetate for metastatic disease. |
| Expansion Cohort 7 | EXPERIMENTAL | Stage IV non-squamous NSCLC subjects who have radiographically progressed on or after treatment with one prior immune checkpoint inhibitor (ICI) (anti-PD-1 or anti-PD-L1) therapy. |
| Expansion Cohort 8 | EXPERIMENTAL | Stage IV non-squamous NSCLC subjects with positive PD-L1 expression and without prior systemic anticancer therapy. |
| Expansion Cohort 9 | EXPERIMENTAL | Stage IV nonsquamous NSCLC subjects with sensitizing EGFR mutation who have radiographically progressed during or following prior treatment with an EGFR-targeting TKI. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy. |
| Expansion Cohort 10 | EXPERIMENTAL | RCC subjects with non-clear cell histology who have had up to one prior VEGFR-targeting TKI therapy. |
| Expansion Cohort 11 | EXPERIMENTAL | TNBC subjects who have radiographically progressed during or following treatment with at least one prior systemic anticancer therapy. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy. |
| Expansion Cohort 12 | EXPERIMENTAL | OC subjects (including primary peritoneal cancer and fallopian tube cancer) who have platinum-resistant or refractory disease who have had up to two lines of prior systemic anticancer therapy. |
| Expansion Cohort 13 | EXPERIMENTAL | EC subjects (serous or endometrioid histology) who have radiographically progressed during or following treatment with at least one prior systemic anticancer therapy. |
| Expansion Cohort 14 | EXPERIMENTAL | HCC subjects (Child-Pugh score A) who have not received prior systemic anticancer therapy. |
| Expansion Cohort 15 | EXPERIMENTAL | GC/GEJC/LEC subjects who have radiographically progressed during or following platinum-containing or fluoropyrimidine-containing chemotherapy. |
| Expansion Cohort 16 | EXPERIMENTAL | CRC subjects who have radiographically progressed during or following systemic chemotherapy that contained fluoropyrimidine in combination with oxaliplatin or irinotecan. |
| Expansion Cohort 17 | EXPERIMENTAL | H\&N cancer subjects who have radiographically progressed during or following prior platinum-containing chemotherapy. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy. |
| Expansion Cohort 18 | EXPERIMENTAL | DTC subjects (follicular, papillary, and poorly differentiated histologies) who are radioactive iodine (RAI) refractory or deemed ineligible for treatment with RAI. |
| Expansion Cohort 19 (SAC) | EXPERIMENTAL | UC subjects (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior ICI (anti-PD-1 or anti-PD-L1). Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression. |
| Expansion Cohort 20 (SAC) | EXPERIMENTAL | Stage IV non-squamous NSCLC subjects who have radiographically progressed on or after treatment with one prior ICI (anti-PD-1 or anti-PD-L1). Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression. |
| Expansion Cohort 21 (SAC) | EXPERIMENTAL | Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC. Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression. |
| Expansion Cohort 22 (SAA) | EXPERIMENTAL | Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC. Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression. |
| Expansion Cohort 23 | EXPERIMENTAL | Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC |
| Expansion Cohort 24 | EXPERIMENTAL | Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with at least one NHT and have received docetaxel for mCRPC |
| Cabozantinib capsules and tablets | EXPERIMENTAL | Subjects will be enrolled in cohorts at different dose levels in order to determine the maximum tolerated dose of cabozantinib. Initially, subjects enrolled will receive the capsule formulation; other subjects will receive the tablet formulation. |
| All subjects | EXPERIMENTAL | All subjects will receive daily XL184, and two single doses of rosiglitazone, 3 weeks apart |
| 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 |
|---|---|---|
| Cabozantinib | DRUG | Administered as specified in the parent study. |
| Zanzalintinib | DRUG | Administered as specified in the parent study. |
| Atezolizumab | DRUG | Administered as specified in the parent study. |
| Nivolumab | DRUG | Administered as specified in the parent study. |
| Abiraterone | DRUG | Administered as specified in the parent study. |
| Prednisone | DRUG | Administered as specified in the parent study. |
| Enzalutamide | DRUG | Administered as specified in the parent study. |
| Abiraterone Acetate | DRUG | Supplied as 500 mg tablets; administered orally daily at 1000mg with prednisone 5 mg orally bid |
| Docetaxel | DRUG | Docetaxel will be administered by IV infusion at a starting dose of 75mg/m2 on Day 1 of each 21-day cycle. |
| Ipilimumab | BIOLOGICAL | Specified dose on specified days. |
| Cabozantinib-matched placebo | DRUG | Specified dose on specified days. |
| Placebo | DRUG | Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally. |
| Sorafenib | DRUG | Supplied as 200-mg tablets; administered orally twice daily at 400 mg |
| Cabozantinib tablets | DRUG | - |
| Placebo tablets | DRUG | - |
| Everolimus (Afinitor) tablets | DRUG | - |
| XL184 | DRUG | Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily |
| Afatinib | DRUG | 40 mg orally once daily for each 28-day cycle. Treatment will continue until disease progression or intolerable toxicity or other reason for discontinuation up to 45 months. |
| Regorafenib | DRUG | 160 mg orally once daily for the first 21 days of each 28-day cycle. Treatment will continue until disease progression or intolerable toxicity or other reason for discontinuation up to 45 months. |
| Pembrolizumab | BIOLOGICAL | Given IV |
| Blood for plasma biomarkers | PROCEDURE | Baseline, cycle 1 day 8, cycle 1 day 15, and day 1 of every cycle thereafter |
| Tissue biopsy | PROCEDURE | Baseline, before start of cycle 2, and time of progression |
| Trastuzumab | DRUG | - |
| Cytoreductive nephrectomy | PROCEDURE | Surgery removing as much tumor tissue as possible, possibly including surrounding tissues. |
| Transarterial Chemoembolization | PROCEDURE | TACE treatment will be administered using either the DEB-TACE or cTACE modality in a series of up to 3 individual procedures within the 9-12 weeks following Day 21 (= cycle 1 day 21) of a patient's first infusion of nivolumab/ipilimumab. The first TACE treatment should start no more than 7 working days after being cycle 1 day 21. |
| Cystectomy | PROCEDURE | Patients will receive three cycles of treatment prior to cystectomy unless they discontinue treatment for unacceptable toxicity or progressive disease by RECIST v1.1 or withdraw consent. |
| Panitumumab | BIOLOGICAL | The FDA approved dose for panitumumab is 6mg/kg IV, every two weeks. This is the dose and schedule that will be used in this study. |
| Lu-177 | DRUG | Currently, the only FDA-approved PRRT consists of dotatate, a somatostatin analogue, radiolabeled with Lutetium-177 (Lu177), a beta-minus emitter (brand name Lutathera). Lu177 induces cell death via DNA strand breaks, caspase-3 apoptosis, and interfering with DNA-PK expression (which is associated with DNA repair). PRRT with Lu-177 DOTATATE is a targeted, intravenous therapy inducing DNA damage by delivering ionizing radiation to somatostatin receptor positive tumors. |
| 13-cis-retinoic acid | DRUG | 13-cis-retinoic acid at 80mg/m2/dose twice daily for two consecutive weeks (14 days) out of every four weeks (28 days, +/- 3 days). |
| Durvalumab | DRUG | infusion |
| Tremelimumab | DRUG | infusion |
| Cabozantinib S-malate | DRUG | Given PO |
| Enfortumab Vedotin | DRUG | Given IV |
| Quality-of-Life Assessment | OTHER | Ancillary studies |
| Questionnaire Administration | OTHER | Ancillary studies |
| cabozantinib capsules | DRUG | cabozantinib capsules administered as 25-mg and 100-mg strengths once-daily until disease progression |
| 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. |
Key Inclusion Criteria: * Eligible to continue receiving the study treatment in the parent study (that is, has not met parent study discontinuation/withdrawal criteria). * Continuing to derive clinical benefit from the study treatment at the time of transition from the parent study as assessed by t...
Top 11 of 13 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Eli Lilly and Company | LLY | 4 | PHASE3 | Selpercatinib, LOXO-292 |
| Novartis AG Sponsored ADR | NVS | 3 | PHASE3 | Dabrafenib, trametinib, Spartalizumab, KFA115 |
| Exelixis, Inc. | EXEL | 3 | PHASE3 | Cabozantinib, Zanzalintinib |
| Merck & Co., Inc. | MRK | 1 | PHASE2 | Pembrolizumab |
| Apollomics Inc. Class A | APLM | 1 | PHASE2 | APL-101 |
| Pfizer Inc. | PFE | 2 | PHASE1 | PF-07799933, binimetinib, PF-07799544 |
| Hoffmann-La Roche | RHHBY | 1 | PHASE2 | Entrectinib |
| Gilead Sciences, Inc. | GILD | 1 | PHASE2 | Sacituzumab govitecan |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
| OPKO Health, Inc. | OPK | 1 | PHASE1 | MDX2001 |
| Bayer | BAYRY | 1 | - | Sorafenib |
XL184, also known as cabozantinib, is an investigational small molecule being studied for the treatment of several advanced malignancies, including glioblastoma, papillary thyroid cancer, non-small-cell lung cancer, lymphoma, and thyroid cancer. It is being developed by Exelixis, Inc. (EXEL) and is currently in clinical development.
XL184, or cabozantinib, is a small molecule that targets multiple receptor tyrosine kinases involved in tumor growth and angiogenesis. It is being studied in oncology for its potential to inhibit pathways that drive cancer progression.
XL184 is being developed by Exelixis, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol EXEL. The drug is an investigational small molecule in clinical development for various oncology indications.
XL184 is in Phase 1 and Phase 2 clinical trials. It is an investigational drug and has not been approved by the FDA. Clinical trials have been completed for advanced malignancies, non-small-cell lung cancer, glioblastoma multiforme, and glioblastoma.
XL184 has been studied in several completed clinical trials, including NCT00215605 in advanced malignancies, NCT00596648 in non-small-cell lung cancer, NCT00704288 in glioblastoma multiforme, and NCT00960492 in glioblastoma. These trials were conducted in the United States.
Yes, XL184 is also known as cabozantinib. It is an investigational small molecule being developed by Exelixis, Inc. for the treatment of various cancers, including glioblastoma, thyroid cancer, and non-small-cell lung cancer.