XL092 for Prostate Cancer

(PRO-XL Trial)

Overseen By Susan Sharry

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Small molecule inhibitors

Disqualifiers: Brain metastases, Uncontrolled hypertension, Active infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the oral tablet XL092 in treating prostate cancer after 16 weeks and to assess its safety. Participants will take XL092 daily and visit the clinic regularly for tests and checkups. Men with confirmed metastatic prostate cancer, whose previous treatment with a specific drug failed to halt progression, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but it mentions a washout period (time without taking certain medications) for prohibited medications before starting the study. Some medications, like megestrol acetate and certain anticoagulants, are allowed, but others may require approval from the Principal Investigator.

Is there any evidence suggesting that XL092 is likely to be safe for humans?

Research shows that XL092 has a manageable safety profile, with side effects similar to those expected from comparable treatments. Earlier studies reported no unexpected adverse reactions, suggesting that XL092 might be well-tolerated. However, individual experiences can vary with any treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

XL092 is unique because it targets cancer cells with a new approach compared to traditional treatments for prostate cancer, such as hormone therapy, chemotherapy, or surgery. Most of these standard treatments focus on reducing hormone levels or removing cancerous tissue. In contrast, XL092 is an oral tablet that works by inhibiting multiple receptor tyrosine kinases, which are involved in tumor growth and blood vessel formation. Researchers are excited about XL092 because its once-daily oral administration offers a convenient alternative to more invasive treatments and has the potential to be effective with fewer side effects.

What evidence suggests that XL092 might be an effective treatment for prostate cancer?

Research shows that XL092, a new cancer treatment, looks promising for prostate cancer. Early studies found that XL092 effectively fights tumors by targeting specific proteins in cancer cells, stopping their growth. Patients tolerated it well, with manageable side effects. Initial results also suggest it could work well with other treatments, like atezolizumab, for those who have tried other options. These findings make XL092 an exciting option for further study in prostate cancer treatment. ^{2 4 6 7 8}

Who Is on the Research Team?

Umang Swami, MD

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic castration-resistant prostate cancer. Participants will be taking an oral tablet called XL092 once a day and must return to the clinic regularly for checkups and tests.

Inclusion Criteria

Able to provide informed consent and willing to sign an approved consent form

Radiographic evidence of metastatic disease

My prostate cancer is confirmed without being a small cell type.

Exclusion Criteria

I haven't had radiation for bone metastasis or any other type within 2 weeks before starting the study treatment.

Other clinically significant disorders that would preclude safe study participation

I have not had major surgery recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the study drug XL092, an oral tablet taken once per day on a 28-day cycle, for 16 weeks

16 weeks

Regular clinic visits for checkups and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• XL092

Trial Overview The study is testing the effectiveness of XL092 in treating prostate cancer after 16 weeks of treatment. It also aims to evaluate the safety profile of this medication when taken daily as an oral tablet.

How Is the Trial Designed?

Group I: Treatment: All Patients Experimental Treatment 1 Intervention

XL092 is an oral tablet that will be taken once per day on a 28 day cycle. Participants will take a 100mg dose. Dose reductions to 60mg or 40mg may apply for in cases of dose interruption due to treatment-related toxicity.

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Exelixis

Industry 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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06568562

Study Details | NCT06568562 | XL092 in Patients With ... The purpose of this study is to determine how well the study drug XL092 is helping to treat a participant's cancer after 16 weeks of treatment.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS285

PRO-XL: A phase II study of zanzalintinib (XL092) in ... Prior studies have demonstrated a significant VEGF expression in LNCaP tumors and locally recurrent prostate cancer after radiotherapy.

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-dose-escalation-results-phase-1-stellar-001

Exelixis Announces Dose-Escalation Results from the Phase ... Both single-agent XL092 and XL092 in combination with atezolizumab demonstrated encouraging efficacy and safety in a heavily pretreated patient population.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02460-7/fulltext

481P A phase I first-in-human study of XL092 in patients ... Conclusions. XL092 demonstrated a manageable safety profile with no unexpected AEs based on current RTK inhibitors. PK, PD, and efficacy data support selection ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9890135/

Preclinical Characterization of XL092, a Novel Receptor ... In summary, XL092 was shown to have significant antitumor and immunomodulatory activity in animal models both alone and in combination with immune checkpoint ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06568562

XL092 in Patients With Metastatic Castration-Resistant ... The purpose of this study is to determine how well the study drug XL092 is helping to treat a participant's cancer after 16 weeks of treatment.

7. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-initiation-phase-1b-trial-evaluating-xl092

Exelixis Announces Initiation of Phase 1b Trial Evaluating ... Researchers estimate that in 2020, 43,000 people were diagnosed with metastatic CRPC, which has a median survival of less than two years.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02460-7/pdf

481P A phase I first-in-human study of XL092 in patients ( ... Conclusions: XL092 demonstrated a manageable safety profile with no unexpected AEs based on current RTK inhibitors.