XL092 + Immunotherapy for Cancer

(STELLAR-001 Trial)

Recruiting at 91 trial locations

Overseen By Backup or International

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Exelixis

Must not be taking: Kinase inhibitors, Anticancer antibodies

Disqualifiers: Brain metastases, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

325 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study treatment. Specifically, you must not have taken any small molecule kinase inhibitors within 2 weeks, or anticancer antibodies, systemic chemotherapy, or hormonal anticancer therapy within 4 weeks before the first dose. Additionally, certain medications cannot be used during the trial.

What data supports the effectiveness of the drug XL092 + Immunotherapy for Cancer?

Research shows that drugs targeting the PD-1/PD-L1 pathway, like Atezolizumab (also known as Tecentriq) and Avelumab (also known as Bavencio), have shown impressive benefits in treating various cancers by helping the immune system attack cancer cells more effectively. ^{1 2 3 4 5}

What safety data exists for XL092 and immunotherapy treatments like Atezolizumab and Avelumab?

Immunotherapy treatments, including those like Atezolizumab and Avelumab, can cause immune-related adverse events (irAEs), which are side effects that occur when the immune system attacks normal tissues. These side effects can range from mild to severe and may include autoimmune diseases. It's important for doctors to monitor these side effects in patients receiving immunotherapy. ^{6 7 8 9 10}

What makes the drug XL092 + Immunotherapy unique for cancer treatment?

The drug XL092 combined with immunotherapy is unique because it potentially enhances the body's immune response against cancer cells, which may offer a novel approach compared to traditional treatments that primarily target the cancer cells directly. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial is testing a new drug called XL092 by itself and with two other drugs, atezolizumab and avelumab. It targets patients with advanced solid tumors who may not respond to current treatments. XL092 aims to stop cancer cells from growing, while atezolizumab and avelumab help the immune system fight the cancer. Atezolizumab is approved for various cancers, including breast and urothelial carcinoma, and has shown efficacy in combination with chemotherapy.

Eligibility Criteria

This trial is for adults with advanced solid tumors that are inoperable or metastatic, and who have tried other treatments without success. They must be mostly recovered from previous treatment side effects, not pregnant, able to use contraception, and have good organ function. People with certain cancers like colorectal cancer must meet specific genetic criteria.

Inclusion Criteria

I have recovered from previous treatment side effects, or they are mild and stable.

I am not pregnant and can become pregnant.

My colon or rectum cancer is advanced, cannot be surgically removed, and lacks certain genetic mutations.

Exclusion Criteria

I have not received a live vaccine within the last 30 days.

I have previously been treated with XL092, PD-L1/PD-1 inhibitors, regorafenib, or TAS-102 depending on my trial cohort.

I haven't had radiation for bone metastasis in the last 2 weeks or any other radiation in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Subjects will accrue in cohorts to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for XL092 alone and in combination with immune checkpoint inhibitors (ICIs)

Up to 24 months

Cohort-Expansion

The MTD or recommended dose from the dose-escalation stage is further explored in specific cancer types to evaluate preliminary efficacy

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

Treatment Details

Interventions

• Atezolizumab
• Avelumab
• XL092

Trial Overview The study tests XL092 alone or combined with Atezolizumab or Avelumab in patients with various solid tumors. It's an early-phase trial to check safety, how the body processes the drugs (pharmacokinetics), their effect on tumor markers, and initial effectiveness against the cancer.

Participant Groups

Group I: XL092 Single-Agent Expansion Cohorts Experimental Treatment 1 Intervention

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).

Group II: XL092 Single-Agent Dose-Escalation Cohorts Experimental Treatment 1 Intervention

Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design.

Group III: XL092 + Avelumab Dose-Escalation Cohorts Experimental Treatment 2 Interventions

Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.

Group IV: XL092 + Atezolizumab Expansion Cohorts Experimental Treatment 2 Interventions

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).

Group V: XL092 + Atezolizumab Dose-Escalation Cohorts Experimental Treatment 2 Interventions

Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.

Who Is Running the Clinical Trial?

Exelixis

Lead Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Findings from Research

The first-in-human study of MK-4830, a novel IgG4 monoclonal antibody targeting the ILT4 receptor, showed it was well tolerated with no dose-limiting toxicities among 84 patients with advanced solid tumors.

In combination with pembrolizumab, MK-4830 demonstrated promising antitumor activity, with 11 out of 34 patients achieving objective responses, including some who had previously progressed on other therapies, suggesting enhanced effectiveness in certain tumor microenvironments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors. Siu, LL., Wang, D., Hilton, J., et al.[2023]

Anti-CTLA4 and anti-PD1/PD-L1 immunotherapies represent a significant shift in cancer treatment by enhancing the immune system's ability to fight tumors rather than directly targeting the tumor cells themselves.

These immunotherapies can lead to unique immune-related adverse events due to the activation of the immune system against normal tissues, necessitating changes in clinical management to address potential autoimmune reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Champiat, S., Michot, JM., Lambotte, O.[2019]

In a study analyzing nationwide insurance claims data from 92,858 patients over 8 years, it was found that patients receiving immune checkpoint inhibitors had a 1.50-4.00 times higher risk of developing immune-related adverse events (irAEs) compared to those receiving chemotherapy or targeted therapy.

Among the immunotherapy agents, nivolumab was associated with a higher risk of irAEs than pembrolizumab, highlighting the importance of monitoring these adverse effects in cancer patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data analyses unveiled the immune-related adverse effects of immune checkpoint inhibitors across cancer types. Wang, F., Yang, S., Palmer, N., et al.[2023]

In a study of 1535 patients receiving high-dose interleukin-2 (IL-2) therapy, those who experienced immune-related adverse events (irAEs) had significantly better tumor control (71% vs. 56%) and overall survival, particularly in metastatic melanoma (median 48 months vs. 18 months) and metastatic renal cell cancer (median 60 months vs. 40 months).

The majority of irAEs were related to IL-2 therapy, primarily manifesting as vitiligo and thyroid dysfunction, indicating that while these adverse events are concerning, they may also signal a beneficial immune response that enhances treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the PROCLAIMSM registry. Curti, B., Daniels, GA., McDermott, DF., et al.[2018]

Harnessing the immune system for cancer treatment has significantly improved patient outcomes, leading to extended life and even cures, but it can also trigger serious side effects like cytokine release syndrome and neurotoxicity.

The article reviews the biological mechanisms behind these immune-mediated adverse effects and discusses industry strategies using laboratory models to better assess safety risks in immune-oncology treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current nonclinical approaches for immune assessments of immuno-oncology biotherapeutics. Grimaldi, C., Ibraghimov, A., Kiessling, A., et al.[2023]

Recent cancer treatments, including monoclonal antibodies and kinase inhibitors, have been developed to specifically target cancer pathways, showing promise in improving cancer control.

However, these therapies are associated with significant gastrointestinal and hepatic toxic effects, such as diarrhea and liver damage, which can lead to treatment discontinuation and reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug insight: gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy. Loriot, Y., Perlemuter, G., Malka, D., et al.[2016]

References

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First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors. [2023]

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Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial. [2023]

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[Management of adverse events associated with cancer immunotherapy]. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Real-world data analyses unveiled the immune-related adverse effects of immune checkpoint inhibitors across cancer types. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the PROCLAIMSM registry. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Current nonclinical approaches for immune assessments of immuno-oncology biotherapeutics. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Drug insight: gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy. [2016]

11. United States pubmed.ncbi.nlm.nih.gov

Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobulin-Like Domain Containing Receptor 2 (ILDR2). [2021]

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The immunocytokine L19-IL2: An interplay between radiotherapy and long-lasting systemic anti-tumour immune responses. [2021]

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Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non-Small Cell Lung Cancer Patients. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Interleukin-2 signals converge in a lymphoid-dendritic cell pathway that promotes anticancer immunity. [2022]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Nanomedicine-Based Gene Delivery for a Truncated Tumor Suppressor RB94 Promotes Lung Cancer Immunity. [2022]