XL092 + Immuno-Oncology Agents for Solid Tumors
(STELLAR-002 Trial)
Recruiting in Palo Alto (17 mi)
+143 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Exelixis
Must not be taking: Anticoagulants, Complementary medicines
Disqualifiers: Brain metastases, Uncontrolled illness, Pregnancy, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called XL092 alone and with other cancer drugs in patients with advanced solid tumors. The goal is to see if these treatments can safely stop or slow tumor growth and help the immune system fight cancer more effectively.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you must stop taking your current medications. However, certain medications like small molecule kinase inhibitors, anticancer antibodies, and some complementary medicines must be stopped 1-4 weeks before starting the trial treatment, depending on the specific cohort.
What data supports the effectiveness of the drug XL092 in combination with immuno-oncology agents for solid tumors?
The research highlights the effectiveness of combining targeted therapies and immunological agents in treating solid tumors, which has led to significant improvements in survival rates. This suggests that using XL092, a targeted therapy, with immuno-oncology agents could potentially enhance treatment outcomes for solid tumors.
12345What safety information is available for XL092 and similar immuno-oncology treatments?
Immuno-oncology treatments, like those involving immune checkpoint inhibitors, can cause immune-related side effects, which are often mild but can include inflammation in various parts of the body. It's important for patients to be monitored for these side effects, even after stopping treatment, as they can occur later.
678910What makes the drug XL092 unique for treating solid tumors?
XL092 is unique because it combines with immuno-oncology agents to target solid tumors, potentially enhancing the immune system's ability to fight cancer. This approach is part of a broader trend in cancer treatment that focuses on using the body's immune response to combat tumors, which differs from traditional chemotherapy that directly attacks cancer cells.
2361112Eligibility Criteria
This trial is for adults with various advanced solid tumors, including specific types of lung, kidney, liver, prostate, bladder and colorectal cancers. Participants must have a certain level of physical fitness (KPS ≥ 70%), adequate organ function, agree to use contraception if fertile, and not be pregnant. They should not have received certain recent treatments or have other active cancers (except some localized ones).Inclusion Criteria
My organs and bone marrow are working well.
I can provide samples of my tumor, either from previous tests or new ones if safe.
My cancer is advanced and cannot be removed by surgery.
+15 more
Exclusion Criteria
I haven't taken any kinase inhibitor medication in the last 2 weeks.
Pregnant or lactating females
I have not received a live vaccine in the last 30 days.
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose-Escalation
Participants receive Zanzalintinib alone or in combination with immuno-oncology agents to determine the recommended dose
12-24 weeks
Expansion
The safety and efficacy of Zanzalintinib as monotherapy and in combination therapy are evaluated in tumor-specific cohorts
up to 24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
Participant Groups
The study tests XL092 alone or combined with immune therapies: nivolumab; nivolumab plus ipilimumab; or nivolumab plus relatlimab. It's in Phase 1b to check safety and how the body processes these drugs while also looking at early signs of their effectiveness against tumors.
7Treatment groups
Experimental Treatment
Group I: Zanzalintinib Single-Agent Expansion CohortsExperimental Treatment1 Intervention
Group II: Zanzalintinib + Nivolumab Expansion CohortsExperimental Treatment2 Interventions
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
Group III: Zanzalintinib + Nivolumab Dose-Escalation CohortsExperimental Treatment2 Interventions
Approximately 12 subjects will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
Group IV: Zanzalintinib + Nivolumab + Relatlimab Expansion CohortsExperimental Treatment2 Interventions
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
Group V: Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation CohortsExperimental Treatment2 Interventions
Approximately 12 subjects will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
Group VI: Zanzalintinib + Nivolumab + Ipilimumab Expansion CohortsExperimental Treatment3 Interventions
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
Group VII: Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation CohortsExperimental Treatment3 Interventions
Approximately 12 subjects will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Exelixis Clinical Stie #46Austin, TX
Exelixis Clinical Site #87Lone Tree, CO
Exelixis Clinical Site #6New York, NY
Exelixis Clinical #14Baltimore, MD
More Trial Locations
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Who Is Running the Clinical Trial?
ExelixisLead Sponsor
References
Enhancement of lexatumumab-induced apoptosis in human solid cancer cells by Cisplatin in caspase-dependent manner. [2017]This study was designed to evaluate the apoptotic effect of mapatumumab or lexatumumab, human agonistic antibodies that target the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2), in combination with chemotherapeutic agents, against human solid cancer cells.
Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients with Advanced Solid Tumors. [2021]Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-in-human study evaluated MEDI0562 in adults with advanced solid tumors.
[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.
Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study. [2019]A phase I study assessed the safety, tolerability, pharmacokinetics, and preliminary antitumor effect of mapatumumab, a fully-human agonist monoclonal antibody to the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1, DR4), in combination with paclitaxel and carboplatin.
Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients With Advanced NSCLC With BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018. [2021]Immune-checkpoint inhibitor (ICI) efficacy in patients with NSCLC harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF-, HER2-, MET-, and RET-NSCLC in a real-world setting.
Primer on immuno-oncology and immune response. [2014]Advances in the understanding of the immunogenicity of tumors have provided the basis for immuno-oncology, the development of immunotherapeutic agents that augment the patient's antitumor immunity and disrupt the immune-regulatory circuits that allow tumors to evade the immune system. Two immunomodulatory agents recently have been introduced for the treatment of malignancy: sipuleucel-T and ipilimumab. Unlike cytotoxic chemotherapy, immunotherapies stimulate the patient's immune system to mount or augment existing endogenous antitumor immune responses. Both agents have demonstrated significant improvements in long-term overall survival in patients. Like other immunotherapies, sipuleucel-T and ipilimumab also are characterized by adverse events that manifest as immune-related inflammatory conditions that typically are low grade. Management guidelines have been developed and emphasize early recognition of the signs and symptoms of immune-related adverse events and treatment with corticosteroids. Because these events can manifest even after the cessation of therapy, patients treated with immunotherapies should continue to be followed by their oncology team and other healthcare providers.
Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. [2022]The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities.
Real-world data analyses unveiled the immune-related adverse effects of immune checkpoint inhibitors across cancer types. [2023]Immune checkpoint inhibitors have demonstrated significant survival benefits in treating many types of cancers. However, their immune-related adverse events (irAEs) have not been systematically evaluated across cancer types in large-scale real-world populations. To address this gap, we conducted real-world data analyses using nationwide insurance claims data with 85.97 million enrollees across 8 years. We identified a significantly increased risk of developing irAEs among patients receiving immunotherapy agents in all seven cancer types commonly treated with immune checkpoint inhibitors. By six months after treatment initialization, those receiving immunotherapy were 1.50-4.00 times (95% CI, lower bound from 1.15 to 2.16, upper bound from 1.69 to 20.36) more likely to develop irAEs in the first 6 months of treatment, compared to matched chemotherapy or targeted therapy groups, with a total of 92,858 patients. The risk of developing irAEs among patients using nivolumab is higher compared to those using pembrolizumab. These results confirmed the need for clinicians to assess irAEs among cancer patients undergoing immunotherapy as part of management. Our methods are extensible to characterizing the effectiveness and adverse effects of novel treatments in large populations in an efficient and economical fashion.
Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. [2021]To provide an overview of immune checkpoint inhibitors (ICIs) safety profile using the Italian spontaneous adverse drug reaction (ADR) reporting system.
Application of a patient-centered reverse translational systems-based approach to understand mechanisms of an adverse drug reaction of immune checkpoint inhibitors. [2022]Immunotherapy became a key pillar of cancer therapeutics with the approvals of ipilimumab, nivolumab, and pembrolizumab, which inhibit either cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed death-1 (PD-1) that are negative regulators of T-cell activation. However, boosting T-cell activation is often accompanied by autoimmunity, leading to adverse drug reactions (ADRs), including high grade 3-4 colitis and its severe complications whose prevalence may reach 14% for combination checkpoint inhibitors. In this research, we investigated how mechanistic differences between anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab and pembrolizumab) affect colitis, a general class toxicity. The data analytical platform Molecular Health Effect was utilized to map population ADR data from the US Food and Drug Administration (FDA) Adverse Event Reporting System to chemical and biological databases for hypothesis generation regarding the underlying molecular mechanisms causing colitis. Disproportionality analysis was used to assess the statistical relevance between adverse events of interest and molecular causation. We verified that the anti-CTLA-4 drug is associated with an approximately three-fold higher proportional reporting ratio associated with colitis than those of the anti-PD-1 drugs. The signal of the molecular mechanisms, including signaling pathways of inflammatory cytokines, was statistically insignificant to test the hypothesis that the severer rate of colitis associated with ipilimumab would be due to a greater magnitude of T-cell activation as a result of earlier response of the anti-CTLA-4 drug in the immune response. This patient-centered systems-based approach provides an exploratory process to better understand drug pair adverse events at pathway and target levels through reverse translation from postmarket surveillance safety reports.
CAR-T "the living drugs", immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy. [2023]New advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibody-drug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CAR-T cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CAR-T cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a "do-not-eat-me" immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR- T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.
Novel and Expanded Oncology Drug Approvals of 2016-PART 1: New Options in Solid Tumor Management. [2021]The nonradiologic medical management of solid tumors has evolved from the use of traditional cytotoxic agents to modern targeted therapies, monoclonal antibodies, and immunotherapies. Advances in the understanding of cancer biology and therapeutic strategies have resulted in increasing numbers of new drug applications and approvals. Consequently, practicing oncologists need to learn how the newly available agents function and what toxicities to watch for, as well as ways to optimize the use of both new drugs and previously approved drugs with new indications. In 2016, the US Food and Drug Administration approved three novel drugs for the treatment of solid malignancies-olaratumab in selected patients with soft-tissue sarcoma, atezolizumab for the treatment of bladder cancer, and rucaparib for the treatment of ovarian cancer; also in 2016, the use of previously approved anticancer agents (including atezolizumab) was expanded into 11 new patient populations. The diversity of options for patients is evident in the broad range of the 2016 approvals, which include immune checkpoint inhibitors, targeted therapies, monoclonal antibodies, and traditional cytotoxic agents. This article focuses on the new agents and indications that emerged in 2016 for solid tumor treatment. We review the drug indications, mechanisms of action, pivotal trial data, pertinent toxicities, use in special populations, and the appropriate clinical contexts for treatment planning.