Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as XL092, Multi-kinase Inhibitor XL092
Zanzalintinib · 29 trials · 63 indications
Defined as the time from randomization to the earlier of either radiographic PD per RECIST 1.1 as determined by the BIRC or death from any cause
Defined as the proportion of subjects with the best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 as determined by the BIRC that is confirmed at a follow-up assessment ≥ 28 days later
Recommended phase 2 dose (RP2D) of XL-092 with Durvalumab plus Tremelimumab will be determined per a Dose Limiting Toxicity period of 28 days during the Safety Lead-in period using CTCAE v5.0 criteria.
Proportion of patients with Complete Response (CR) or Partial Response (PR), per immune modified RECIST v1.1. Per imRECIST: CR: -100% Change in Sum of Diameters from Baseline (non-target lesion). PR: ≤ -30% change in sum of diameters from baseline.
PFS is defined as the time from the date of initiation of zanzalintinib treatment to progression or death, whichever occurs first. The alive patients without progression are censored at the last follow-up.
ORR will include complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST version 1.1.
Will be reported with 95% exact confidence interval.
The proportion of participants who have not demonstrated radiographic progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or demonstrated clinical progression-free survival (PFS) at 12 months after the start of study treatment. Twelve-month landmark PFS rate will be obtained with 95% confidence interval using the Kaplan-Meier method.
To evaluate the disease control rate at 16 weeks in metastatic castrate-resistant prostate cancer (mCRPC) patients treated with XL092 after progression on 177Lu-PSMA-617
Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.
For soft tissue lesions, rPFS is defined as the date of Cycle 1 Day 1 to date of radiologic progression of soft tissue lesions per RECIST 1.1 or death whichever occurs first.
ORR is defined as the proportion of patients with partial response and complete response per RECIST version 1.1 criteria at any time prior to 6 months
Defined as the time from randomization to the earlier of either radiographic progressive disease (PD) per RECIST 1.1 as determined by the BICR or death from any cause
Defined as the time from randomization to death due to any cause
Rate of hematologic toxicity including neutropenia, anemia, or thrombocytopenia requiring intervention (transfusions or antibiotics)
Rate of non-hematologic toxicity
12-month PFS based on investigator determination of tumor progression (clinical, radiographic, and/or tumor markers including AFP and hCG)
The MTD will be defined as the dose combination with a dose-limiting toxicities (DLT) rate closest to the target DLT rate of 25%.
The RP2D will be defined as the MTD identified after enrollment to all cohorts.
Safety/Tolerability is measured by the number of participants treated with different dose levels of tegavivint in combination with zanzalintinib who experience dose limiting toxicity adverse events (AE) \>= Grade 3, as defined by Common Terminology Criteria for Adverse Events by CTCAE v5.0.
To estimate the MTD and/or to identify the recommended dose of tegavivint for combination zanzalintinib, the variable is the incidence of DLTs in the first cycle of treatment. Estimation of the MTD(s)/recommended dose(s) will be based on a BOIN dose escalation design and dose expansion to estimate the probability of DLT in the first cycle of treatment for participants in the DDS. Following completion of the combination dose escalation, all safety, Dose-determining analysis set (DDS) The DDS includes all participants from the safety set who either completed a minimum exposure requirement or who had a DLT during the first cycle of treatment. The minimum exposure requirement is defined as having received ≥ 80% of the intended tegavivint + zanzalintinib dose(s) during the first cycle.
To determine the recommended phase 2 dose (RP2D) of tegavivint in combination with zanzalintinib. The dose determining set will include all participants who either completed a minimum exposure requirement or who had a DLT during the first cycle of treatment. The minimum exposure requirement is defined as having received ≥ 80% of the intended tegavivint + zanzalintinib dose(s) during the first cycle. The RP2D of tegavivint in combination with zanzalintinib will be determined by toxicity assessed by NCI CTCAE v5.0 toxicity criteria.
DLTs are defined in the protocol.
Graded using CTCAE version 5.0.
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached or, if the MTD is not reached, until 6 patients have been treated successfully at the highest dose level (which will then be termed the recommended phase II dose (RP2D)).
As assessed by the Investigator per Response Evaluation Criteria in Solid Tumors guideline version 1.1 (RECIST 1.1).
As assessed by the Investigator per RECIST 1.1.
As assessed by the Investigator per RECIST 1.1.
To determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for further evaluation of XL092 when administered alone and in combination with immune checkpoint inhibitors (ICIs) to subjects with advanced solid tumors
To evaluate preliminary efficacy of XL092 when administered alone and in combination with ICIs by estimating ORR as assessed by the Investigator per RECIST 1.1
To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with ICIs for specific cohorts by estimating the percentage of subjects with PFS at 6 months (PFS rate) per RECIST 1.1 as assessed by the Investigator (except for the CRC expansion cohort H)
To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with atezolizumab for subjects with RAS wild-type CRC (Cohort H Treatment Arms H-A and H-B) by estimating overall survival (OS)
| Arm | Type | Description |
|---|---|---|
| Zanzalintinib + Pembrolizumab (+) Berahyaluronidase alfa | EXPERIMENTAL | Participants will receive zanzalintinib in combination with pembrolizumab (+) berahyaluronidase alfa for up to 2 years. |
| Zanzalintinib Monotherapy | EXPERIMENTAL | Participants will receive zanzalintinib for up to 2 years. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo to match zanzalintinib for up to 2 years. |
| XL092 + Nivolumab | EXPERIMENTAL | Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab |
| Sunitinib Malate | ACTIVE_COMPARATOR | Subjects with advanced or metastatic nccRCC will receive an active comparator of sunitinib |
| XL092 + Atezolizumab | EXPERIMENTAL | Participants with mCRC will receive XL092 + atezolizumab. |
| Regorafenib | ACTIVE_COMPARATOR | Participants with mCRC will receive active comparator of regorafenib. |
| Safety Lead-in - Zanzalintinib (XL-092) + Tremelimumab (IV) + Durvalumab (IV) | EXPERIMENTAL | Safety Lead-in: XL-092: The first dose level (dose level 0) will follow the rolling 6 design\*. The participants enrolled in this study part will receive one cycle of XL-092 60 mg orally (PO) daily plus durvalumab 1500 mg intravenously (IV) every 28 days + tremelimumab 300 mg IV once. In cycle 2 and subsequent cycles, participants will receive XL-092 60 mg orally (PO) daily and durvalumab 1500mg IV every 28-day cycles. DLT period will be 28 days. One level dose reduction will be pursued based DLT read of the dose level 0 participants. For dose level -1, XL-092 will be used at 40mg daily dosing, in combo with the same flat dosings for Durvalumab and Tremelimumab. Safety lead in will be 6-12 patients. |
| Zanzalintinib (XL-092) + Tremelimumab (IV) + Durvalumab (IV) (Begin First Cyle Zanzalintinib) | ACTIVE_COMPARATOR | Phase 2: One cycle of XL-092 RP2D PO daily + durvalumab 1500 mg intravenously (IV) every 28 days + tremelimumab 300 mg IV once. XL- 092 RP2D daily and durvalumab will then be continued every 28 days cycles until discontinuation due to disease progression, intolerability, or withdrawal of consent. |
| Zanzalintinib (XL-092) + Durvalumab (IV) + Tremelimumab (IV) (Begin Second Cyle Zanzalintinib) | ACTIVE_COMPARATOR | Phase 2: One cycle of durvalumab 1500 mg IV + tremelimumab 300 mg IV once followed by XL-092 RP2D mg PO Daily + durvalumab 1500 mg IV every 28 days until discontinuation due to disease progression, intolerability, or withdrawal of consent. |
| Zanzalintinib | EXPERIMENTAL | Zanzalintinib 60 mg taken by mouth once daily in 28-day cycles for up to 3 years. |
| Zanzalintinib (XL092) and Nivolumab | EXPERIMENTAL | All subjects will receive zanzalintinib 100mg orally (PO) once daily plus nivolumab standard of care dosing (i.e., 240mg IV every 2 weeks or 480mg IV every 4 weeks) for a total of 12 weeks, followed by restaging scan/evaluation for surgical operability and an adaptive approach that includes (1) surgical resection if the participant is eligible for surgery (Cohort A), (2) up to 48 weeks total (from Cycle 1 Day 1) of zanzalintinib plus nivolumab if the participant has partial response or stable disease but remains inoperable (Cohort B1), or (3) stopping protocol mandated treatment to receive standard of care systemic therapy and continue follow up per protocol if the participant has disease progression (Cohort B2). |
| Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib) | EXPERIMENTAL | CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2. CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study. |
| Treatment (Zanzalintinib) | EXPERIMENTAL | Participants will receive 100 mg Zanzalintinib administered orally once a day in 28-day cycles, starting on cycle 1, day 1, and continued until criteria for removal from study are met. Investigator-choice bone-strengthening agent (BSA) will be selected and administered at a standard dose/interval starting within 30 days of cycle 1, day 1. Non-investigational RT for symptomatic metastases, including bone metastases, is allowed per investigator discretion. Participants must receive at least 1 dose of zanzalintinib prior to treatment pause for RT. Participants may continue study treatment until they are unable to tolerate treatment due to toxicity or demonstrate progression (per RECIST) from the time of initiating treatment. |
| Treatment: All Patients | EXPERIMENTAL | XL092 is an oral tablet that will be taken once per day on a 28 day cycle. Participants will take a 60mg dose. Dose reductions to 40mg or 20mg may apply for in cases of dose interruption due to treatment-related toxicity. |
| Durvalumab + zanzalintinib | EXPERIMENTAL | Participants will receive treatment regimen of durvalumab and zanzalintinib. Each treatment cycle is 28 days. Participants will continue to receive treatment until disease progression, death, or other reasons for withdrawal. |
| Arm A: XL092 | EXPERIMENTAL | Study treatment will be given in 28-day (4 week) cycles. Arm A treatment will consist of XL092 60 mg orally alone and will be taken once daily continuously (Day 1-Day 28). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate. |
| Arm B: XL092 and Nivolumab | EXPERIMENTAL | Study treatment will be given in 28-day (4 week) cycles. Arm B treatment will consist of XL092 60 mg plus nivolumab 480 mg intravenously. XL092 will be taken once daily continuously (Day 1-Day 28) and nivolumab will be administered every 4 weeks (Day 1). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate. |
| Zanzalintinib + Pembrolizumab | EXPERIMENTAL | Participants will receive 4 cycles of once every 3 weeks (Q3W) induction therapy with pembrolizumab and standard of care (SOC) as prescribed by their treating physician. Participants with complete response (CR), partial response (PR), or stable disease (SD) after induction therapy will begin treatment with zanzalintinib and pembrolizumab (maintenance therapy) via intravenous (IV) infusion Q3W. |
| Everolimus | ACTIVE_COMPARATOR | Participants will receive everolimus oral tablets once daily. |
| Zanzalintinib-Matched Placebo + Pembrolizumab | PLACEBO_COMPARATOR | Subjects with R/M HNSCC will receive zanzalintinib-matched placebo + pembrolizumab |
| Phase 1 Dose Escalation | EXPERIMENTAL | - |
| Phase II Dose Expansion | EXPERIMENTAL | Patients will be added at highest zanzalintinib dose tolerated, 40mg or 60mg. |
| Dose Escalation (Dose Level -1) | EXPERIMENTAL | Participants receive the combination of the following drugs in 42-day cycles: * Zanzalintinib at a dose of 20 mg daily on days 1-42 of each cycle * Cetuximab at a dose of 500 mg/m2 on days 1, 15, and 29 of each cycle * Pembrolizumab 400 mg on day 1 of each cycle |
| Dose Escalation (Dose Level 0) | EXPERIMENTAL | Participants receive the combination of the following drugs in 42-day cycles: * Zanzalintinib at a dose of 40 mg daily on days 1-42 of each cycle * Cetuximab at a dose of 500 mg/m2 on days 1, 15, and 29 of each cycle * Pembrolizumab 400 mg on day 1 of each cycle This will be the first dose escalation enrolled. Dose Levels 1 and/or -1 will be enrolled depending on side effects seen in participants enrolled to this cohort. |
| Dose Escalation (Dose Level 1) | EXPERIMENTAL | Participants receive the combination of the following drugs in 42-day cycles: * Zanzalintinib at a dose of 60 mg daily on days 1-42 of each cycle * Cetuximab at a dose of 500 mg/m2 on days 1, 15, and 29 of each cycle * Pembrolizumab 400 mg on day 1 of each cycle |
| Dose Expansion | EXPERIMENTAL | Participants receive the combination of the following drugs in 42-day cycles: * Zanzalintinib will be dosed daily (days 1-42) at the dose identified as recommended phase 2 dose during dose escalation. * Cetuximab at a dose of 500 mg/m2 on days 1, 15, and 29 of each cycle * Pembrolizumab 400 mg on day 1 of each cycle The expansion cohort will begin enrollment after the dose escalation cohorts have completed enrollment. |
| Dose Level 2 (Starting Dose): Zanzalintinib + Paclitaxel | EXPERIMENTAL | Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression. |
| Dose Level 3: Zanzalintinib + Paclitaxel | EXPERIMENTAL | Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression. |
| Dose Level 1 (Reduction): Zanzalintinib + Paclitaxel | EXPERIMENTAL | Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression. |
| Phase 1: Dose Escalation: Dose Level 2 | EXPERIMENTAL | Participants will receive tegavivint as an intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle at the dose level determined by the cohort assignment, combined with zanzalintinib 60 mg taken orally once daily on Days 1 through 28 of every cycle. |
| Phase 1: Dose Escalation: Dose Level 1 | EXPERIMENTAL | Starting Dose Level Participants will receive tegavivint as an intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle at the dose level determined by the cohort assignment, combined with zanzalintinib 60 mg taken orally once daily on Days 1 through 28 of every cycle. |
| Phase 1: Dose Escalation: Dose Level -1 | EXPERIMENTAL | Participants will receive tegavivint as an intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle at the dose level determined by the cohort assignment, combined with zanzalintinib 60 mg taken orally once daily on Days 1 through 28 of every cycle. |
| Phase 2: Dose Expansion | EXPERIMENTAL | Phase 2, participants will be assigned to take zanzalintinib (XL092) and tegavivint at a dosage determine by Phase 1. |
| Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + Ipilimumab | EXPERIMENTAL | Zanzalintinib 40 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
| Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + Ipilimumab | EXPERIMENTAL | Zanzalintinib 60 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
| Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + Ipilimumab | EXPERIMENTAL | Zanzalintinib 20 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
| Expansion: Zanzalintinib + Nivolumab + Ipilimumab | EXPERIMENTAL | Zanzalintinib dose determined in Dose Escalation by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
| Dose Level 1 (starting dose): Zanzalintinib + Eribulin | EXPERIMENTAL | Patients will receive zanzalintinib 40 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle. |
| Dose Level 2: Zanzalintinib + Eribulin | EXPERIMENTAL | Patients will receive zanzalintinib 60 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle. |
| Dose Level -1: Zanzalintinib + Eribulin | EXPERIMENTAL | Patients will receive zanzalintinib 20 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle. |
| Moderate HI | EXPERIMENTAL | Participants with moderate HI will receive a single oral dose of zanzalintinib tablet on Day 1. |
| Matched Healthy Control | ACTIVE_COMPARATOR | Matched healthy control participants will receive a single oral dose of zanzalintinib tablet on Day 1. |
| Zanzalintinib + Nivolumab Dose-Escalation Cohorts | EXPERIMENTAL | Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design. |
| Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation Cohorts | EXPERIMENTAL | Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design. |
| Zanzalintinib + Nivolumab Expansion Cohorts | EXPERIMENTAL | The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts. |
| Zanzalintinib + Nivolumab + Ipilimumab Expansion Cohorts | EXPERIMENTAL | The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts. |
| Zanzalintinib Single-Agent Expansion Cohorts | EXPERIMENTAL | - |
| Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation Cohorts | EXPERIMENTAL | Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design. |
| Zanzalintinib + Nivolumab + Relatlimab Expansion Cohorts | EXPERIMENTAL | The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts. |
| Zanzalintinib + Docetaxel + Prednisone Dose Expansion Cohort | EXPERIMENTAL | Participants with mCRPC, post-androgen receptor pathway inhibitor (post-ARPI), visceral metastases. The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts. |
| Zanzalintinib + DDI Probe Substrates Dose Expansion Cohort | EXPERIMENTAL | Participants in the DDI Cohort. The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts. |
| XL092 Single-Agent Dose-Escalation Cohorts | EXPERIMENTAL | Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design. |
| XL092 Single-Agent Expansion Cohorts | EXPERIMENTAL | The MTD or recommended dose from the dose-escalation stage may be further explored in clear cell renal cell carcinoma (ccRCC), non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), and metastatic castration-resistant prostate cancer (mCRPC). |
| XL092 + Atezolizumab Dose-Escalation Cohorts | EXPERIMENTAL | Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design. |
| XL092 + Atezolizumab Expansion Cohorts | EXPERIMENTAL | The MTD or recommended dose from the dose-escalation stage may be further explored in non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), metastatic castration-resistant prostate cancer (mCRPC), and colorectal cancer (CRC). |
| XL092 + Avelumab Dose-Escalation Cohorts | EXPERIMENTAL | Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design. |
| Name | Type | Description |
|---|---|---|
| Zanzalintinib | DRUG | Oral tablets administered once daily. |
| Pembrolizumab (+) Berahyaluronidase alfa | BIOLOGICAL | Pembrolizumab + berahyaluronidase alfa fixed-dose combination administered via subcutaneous (SC) injection once every 3 weeks (Q3W). |
| Placebo | DRUG | Placebo to match zanzalintinib oral tablets administered once daily. |
| XL092 | DRUG | Specified doses on specified days |
| Nivolumab | DRUG | Specified doses on specified days |
| Sunitinib Malate | DRUG | Specified doses on specified days |
| Atezolizumab | DRUG | Supplied as 1200 milligrams (mg)/20 milliliter (mL) vials; administered as a 1200 mg intravenous (IV) infusion once in a 3-week cycle (q3w). |
| Regorafenib | DRUG | Supplied as 40 mg tablets; administered orally daily at 160 mg for the first 21 days of each 28-day cycle. |
| Durvalumab | DRUG | Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 (CD279) |
| Tremelimumab | DRUG | Tremelimumab is a fully human monoclonal antibody used for the treatment of hepatocellular carcinoma designed to attach to and block CTLA-4, a protein that controls the activity of T cells |
| Angiogram | PROCEDURE | Undergo angiogram |
| Biopsy Procedure | PROCEDURE | Undergo tumor biopsy |
| Biospecimen Collection | PROCEDURE | Undergo blood and urine sample collection |
| Computed Tomography | PROCEDURE | Undergo CT scan |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Single Photon Emission Computed Tomography | PROCEDURE | Undergo SPECT |
| Yttrium-90 Microsphere Radioembolization | PROCEDURE | Given via transartieral radioembolization procedure |
| Investigator Choice of Bone Strengthening Agents (BSA) | DRUG | One BSA will be chosen, at the discretion of the investigator and given intravenously (IV) |
| Non-Investigational Radiation Therapy (RT) | RADIATION | Non-investigational RT is permitted for symptomatic bone metastases. |
| Bone Scan | PROCEDURE | Undergo Bone Scan |
| Computerized tomography (CT) Scan | PROCEDURE | Undergo Imaging |
| Carboplatin | DRUG | Administered as part of SOC therapy as specified in the treatment arm. |
| Paclitaxel | DRUG | Administered as part of SOC therapy as specified in the treatment arm. |
| Nab-paclitaxel | DRUG | Administered as part of SOC therapy as specified in the treatment arm. |
| Pembrolizumab | DRUG | Administered as specified in the treatment arm. |
| Everolimus | DRUG | Administered as specified in the treatment arm. |
| Zanzalintinib-matched Placebo | DRUG | Specified doses on specified days |
| Etoposide Capsule | DRUG | Oral daily for 21 days of each 28 day cycle. |
| Cetuximab | DRUG | Food and Drug Administration (FDA) approved monoclonal antibody directed against the epidermal growth factor (EGFR). |
| Tegavivint | DRUG | 5 mg/kg IV weekly |
| Ipilimumab | DRUG | Ipilimumab will be commercially sourced. |
| Eribulin | DRUG | 1.1 mg/m\^2 dose. |
| Nivolumab + Relatlimab | DRUG | IV administration of nivolumab + relatlimab |
| Prednisone | DRUG | Administered as IV infusion. |
| Docetaxel | DRUG | Administered as oral tablet. |
| DDI Probe Cocktail | DRUG | Midazolam, Warfarin, Omeprazole, and Caffeine administered orally. |
| Avelumab | DRUG | Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w) |
Key Inclusion Criteria: * Histologically confirmed diagnosis of Stage II or III adenocarcinoma of colon or rectum. * Documented local MSI and/or mismatch repair (MMR) test result demonstrating MSS, MSI-low, or pMMR status. * Colon or rectal cancer with completed definitive therapy. * ctDNA-positive...
Zanzalintinib is an investigational oral small molecule kinase inhibitor being developed by Exelixis, Inc. for the treatment of cancer. It is being studied in advanced solid tumors including leiomyosarcoma, renal cell carcinoma, urothelial carcinoma, aggressive variant prostate carcinoma, and colorectal cancer. It is also known as XL092.
Zanzalintinib targets VEGFR2, MET, AXL, and MERTK, a set of receptor kinases involved in tumor growth, angiogenesis, and immune evasion. It belongs to the -tinib class of kinase inhibitors. By inhibiting these targets, zanzalintinib is designed to affect both tumor blood supply and the tumor microenvironment.
Zanzalintinib is being developed by Exelixis, Inc., which trades on Nasdaq under the ticker EXEL. Exelixis is sponsoring the clinical program evaluating zanzalintinib across multiple solid tumor indications, including combinations with immunotherapy and other agents.
Zanzalintinib is investigational and remains in clinical development. Its trials span Phase 1, Phase 2, and Phase 3, including a Phase 3 study in colorectal cancer with molecular residual disease. It has not been approved by the FDA for any indication.
Zanzalintinib is being studied in several trials, including NCT07750158, a Phase 3 study in colorectal cancer with molecular residual disease; NCT07845786, a Phase 2 study with pembrolizumab in squamous NSCLC; NCT07878689, a Phase 1 study with tegavivint in hepatocellular carcinoma; and NCT07773454, a Phase 1 pediatric solid tumor study.
Yes, zanzalintinib is the same drug as XL092. XL092 is the earlier code name used for the compound, and zanzalintinib is its current name. Both refer to the same investigational VEGFR2, MET, AXL, and MERTK kinase inhibitor developed by Exelixis.