535 Participants Needed

LOXO-435 for Bladder Cancer

(FORAGER-1 Trial)

Recruiting at 180 trial locations
PA
Tm
Tq
Pi
Overseen ByPhysicians interested in becoming principal investigators please contact
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Eli Lilly and Company
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new drug, LOXO-435, for treating bladder cancer and other solid tumors with a specific gene change (FGFR3). Researchers aim to determine how well LOXO-435 works alone and in combination with other cancer treatments. People with solid tumor cancers that have this gene change and who have tried other treatments might be suitable for this study. Participants will take LOXO-435 orally, and some may receive it with other cancer drugs intravenously.

As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LOXO-435 is generally well-tolerated when taken alone. In studies where patients took doses of 200 mg twice a day or more, most did not experience severe side effects, indicating a favorable safety profile and promising early results.

The safety of LOXO-435 combined with pembrolizumab, a common cancer treatment, has also been studied. Although specific side effects from this combination are not fully detailed, research on pembrolizumab in other treatments suggests it is usually safe.

The combination of LOXO-435 with both pembrolizumab and enfortumab vedotin is under study as well. Enfortumab vedotin has FDA approval for use with pembrolizumab, indicating a known level of safety.

Overall, early study data suggest that LOXO-435, whether used alone or with other medicines, is generally safe. However, ongoing research will provide more detailed information.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about LOXO-435 for bladder cancer because it offers a fresh approach compared to the current standard treatments, which often include chemotherapy and immunotherapy. LOXO-435 is a targeted therapy that works by inhibiting specific proteins involved in tumor growth, setting it apart from the broader mechanisms of existing options. Additionally, in some trial arms, LOXO-435 is combined with pembrolizumab and enfortumab vedotin, potentially enhancing its effectiveness through a multi-pronged attack on cancer cells. This combination could offer improved outcomes by harnessing the strengths of different treatment types.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

In previous studies, LOXO-435 showed promising results for treating cancers with changes in the FGFR3 gene, such as bladder cancer. It demonstrated strong cancer-fighting effects and was well-tolerated, meaning patients did not experience severe side effects. In this trial, some participants will receive LOXO-435 alone, while others will receive it with pembrolizumab, a type of immune therapy that has shown even more potential in fighting cancer. Additionally, early findings suggest that adding enfortumab vedotin, another cancer drug, could enhance the combination's effectiveness. These results make LOXO-435 a hopeful option for those with FGFR3-altered cancers.12356

Who Is on the Research Team?

C1

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My cancer has a specific genetic change in FGFR3 that can be targeted for treatment.
I have had at least one treatment for my advanced or metastatic cancer.
I may or may not have been treated with FGFR inhibitors before.
See 11 more

Exclusion Criteria

I have a serious heart condition.
Your heart's electrical activity takes longer than normal to reset between beats.
Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Optimization

Phase 1a includes dose escalation and optimization to assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D).

Up to 2 months

Dose Expansion

Phase 1b includes dose expansion cohorts to evaluate the efficacy and safety of LOXO-435 at the RP2D in participants with FGFR3-altered advanced solid tumors.

Up to 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • LOXO-435
Trial Overview 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.
How Is the Trial Designed?
5Treatment groups
Experimental Treatment
Group I: Phase 1b: Cohort B5 LOXO-435 Plus Pembrolizumab Plus Enfortumab VedotinExperimental Treatment3 Interventions
Group II: Phase 1b: Cohort B3 LOXO-435 Plus PembrolizumabExperimental Treatment2 Interventions
Group III: Phase 1b: Cohort B1, B2, B4, and C1 LOXO-435 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Group IV: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose OptimizationExperimental Treatment1 Intervention
Group V: Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose EscalationExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials
2,708
Recruited
3,720,000+
Dr. Daniel Skovronsky profile image

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks profile image

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Loxo Oncology, Inc.

Industry Sponsor

Trials
72
Recruited
11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Citations

A first-in-human phase 1 study of LY3866288 (LOXO-435), ...Conclusions: LY3866288 is well-tolerated with robust clinical activity at multiple DLs, including in erdafitinib refractory mUC. Randomized dose ...
A First-in-Human Phase 1 Study of LY3866288 (LOXO-435 ...In patients treated at 200 mg twice daily and higher, LY3866288 demonstrates a favorable safety profile and promising preliminary antitumor ...
FORAGER-1: A Study of LOXO-435 (LY3866288 ... - Lilly TrialsThe main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other ...
FORAGER-1: A Study of LOXO-435 (LY3866288) in ...The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other ...
LOXO-435 in Patients With Cancer With a Change ...The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other ...
FGFR3 Inhibitor - LOXO-435 Molecular Insights For HCPsFGFR3 aberrations act as oncogenes across tumor types and have been identified in 15% to 20% of advanced urothelial bladder cancers, ~15% of uterine ...
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