What side effects are associated with this type of intervention?

Common treatments for ureteral tumors, particularly those involving FGFR3 inhibitors like LOXO-435, often include targeted therapies. The known side effects of FGFR3 inhibitors can include hyperphosphatemia, dry mouth, fatigue, and gastrointestinal issues such as diarrhea and nausea. Other potential side effects may include skin reactions, such as rash or dry skin, and elevated liver enzymes. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for urothelial carcinoma, which includes ureteral tumors. Notably, Erdafitinib, an FGFR3 inhibitor, has been approved for patients with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 genetic alterations. This approval is particularly relevant as it aligns with the mechanism of action being studied in the LOXO-435 trial. Other treatments for urothelial carcinoma include immune checkpoint inhibitors like Pembrolizumab and Atezolizumab, which have shown efficacy in advanced stages of the disease.

What other types of research exist?

Promising alternatives to LOXO-435 for ureteral tumors include: 1) Nivolumab plus Ipilimumab, which has shown efficacy in advanced renal cell carcinoma; 2) Cabozantinib, another effective treatment for advanced renal cell carcinoma; and 3) Pembrolizumab, which has been used in various solid tumors. These treatments are being explored in clinical trials and may offer new options for patients in 2024.

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Kinase Inhibitor

LOXO-435 for Bladder Cancer

Phase 1

Recruiting

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration for Cohort C (Dose Expansion)

Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable

Must not have

Significant cardiovascular disease

Any serious unresolved toxicities from prior therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 30 months or 2.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing LOXO-435, a new drug, to see if it can help treat advanced cancers with a specific genetic change. It aims to block a gene that helps cancer cells grow. The study will check the drug's safety and effectiveness in these patients. LOX may be a potential effective therapeutic target to treat colorectal cancer.

Who is the study for?

This trial is for adults with advanced or metastatic solid tumors, including bladder cancer, that have a specific gene change (FGFR3). They must have tried all standard treatments or refuse them and be in good physical condition. Pregnant women and those with uncontrolled brain metastases, serious heart conditions, unresolved side effects from prior therapies, or certain eye disorders cannot join.

What is being tested?

The study tests LOXO-435's safety and effectiveness on cancers linked to the FGFR3 gene alteration. Participants will also receive Pembrolizumab. The trial involves different cohorts based on previous treatments and genetic profiles of the tumors. It can last up to 2.5 years.

What are the potential side effects?

Possible side effects include reactions related to immune system activation by Pembrolizumab such as fatigue, skin issues, inflammation of organs; LOXO-435 may cause similar effects due to its targeted action on cancer cells.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is advanced or has spread, and tests show a specific FGFR3 gene change.

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My cancer has a specific genetic change in FGFR3 that can be targeted for treatment.

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I have been treated with an FGFR inhibitor for my condition.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart condition.

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I don't have any serious side effects from past treatments that haven't gone away.

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I do not have any uncontrolled infections or serious health issues.

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I have a history or current signs of extensive tissue calcification.

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I have or might have untreated brain metastases.

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I have a primary brain tumor.

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I have a current eye condition affecting my cornea or retina.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 30 months or 2.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 30 months or 2.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 30 months or 2.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1a: To determine the recommended phase 2 dose (RP2D)/optimal dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs)

Heart rate

Secondary study objectives

Change from baseline in bladder-related symptoms, measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) subscale (BlCS)

Change from baseline in physical function, measured by FACT- Physical Well-being Scale (PWB) subscale

Plasma

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Phase 1b: Cohort C1 LOXO-435 Monotherapy Dose ExpansionExperimental Treatment1 Intervention

LOXO-435 administered orally to participants with advanced solid tumors who have not received a prior FGFR inhibitor.

Group II: Phase 1b: Cohort B3 LOXO-435 Plus PembrolizumabExperimental Treatment2 Interventions

LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV) to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.

Group III: Phase 1b: Cohort B2 LOXO-435 Monotherapy Dose ExpansionExperimental Treatment1 Intervention

LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.

Group IV: Phase 1b: Cohort B1 LOXO-435 Monotherapy Dose ExpansionExperimental Treatment1 Intervention

LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who were previously treated with an FGFR inhibitor.

Group V: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose OptimizationExperimental Treatment1 Intervention

LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma. (Cohort to be implemented as needed, based on Sponsor's discretion.)

Group VI: Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose EscalationExperimental Treatment1 Intervention

LOXO-435 administered orally to participants with FGFR3-altered advanced solid tumors.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~2810

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for ureteral tumors include chemotherapy, immunotherapy, and targeted therapies such as FGFR3 inhibitors. Chemotherapy works by killing rapidly dividing cancer cells, while immunotherapy boosts the body's immune system to recognize and destroy cancer cells. Targeted therapies, like FGFR3 inhibitors (e.g., LOXO-435), specifically block the activity of the FGFR3 protein, which is often mutated in ureteral tumors, leading to uncontrolled cell growth. This targeted approach is crucial for patients with FGFR3 mutations as it directly interferes with the cancer's growth mechanism, potentially leading to more effective and personalized treatment outcomes.

Management of poor-risk metastatic renal cell carcinoma: current approaches, the role of temsirolimus and future directions.Current management and future perspectives of metastatic renal cell carcinoma.Selecting patients for cytoreductive nephrectomy in advanced renal cell carcinoma: who and when.