LY4052031 for Cancer

(NEXUS-01 Trial)

Recruiting at 39 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Disqualifiers: Uncontrolled CNS metastases, Hypercalcemia, Diabetes, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, LY4052031, to determine its safety and effectiveness for individuals with advanced or metastatic solid tumors, such as certain types of bladder, breast, and lung cancers. The study occurs in two stages: one to determine the correct dose and another to evaluate its effectiveness. Candidates may qualify if they have one of these cancers and have not responded to standard treatments. Participants will receive the drug intravenously in varying dosages to identify the best approach. As a Phase 1 trial, this research aims to understand 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 study team or your doctor.

Is there any evidence suggesting that LY4052031 is likely to be safe for humans?

Research shows that LY4052031 is being tested for safety in people with advanced or spreading solid tumors, such as bladder cancer. Earlier studies examined how well people could tolerate LY4052031 and assessed its safety. These studies focused on side effects and how the body processes the drug.

Since this trial is in its early stage, the main goal is to learn about the treatment's safety and optimal dose. Researchers are determining the safest way to administer the drug and the most effective dose with minimal side effects.

While detailed information on side effects is not yet available, early trials like this are crucial to ensure a new treatment's safety before wider use. Researchers will closely monitor participants for adverse reactions and adjust the treatment as needed to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about LY4052031 for cancer because it offers a potentially new approach where current treatments might fall short. Unlike standard therapies that often involve chemotherapy or targeted therapies, LY4052031 is being explored for its unique mechanism of action, which may provide an alternative for patients who do not respond well to existing options. The treatment is administered intravenously in escalating doses to find the optimal dose, which could maximize its effectiveness while minimizing side effects. This dose-optimization process is crucial because it aims to enhance the drug's efficacy and improve patient outcomes compared to traditional treatments.

What evidence suggests that LY4052031 might be an effective treatment for cancer?

Research has shown that LY4052031 is very effective in animal studies for treating various types of tumors. It performs well with different levels of nectin-4, a protein linked to some cancers, even when other treatments have failed. Nectin-4 is a proven target for treating bladder cancer, and similar drugs targeting it have been approved and show promising results. This trial will explore LY4052031 using different dosing strategies, including dose-escalation, dose-optimization, and dose-expansion cohorts, to assess its potential effectiveness in advanced solid tumors, including bladder cancer. However, further studies in humans are needed to confirm its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

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 people with advanced or metastatic solid tumors, including urothelial cancer and various other cancers like lung, breast, esophageal, and more. Participants should have a tumor that's progressed after treatment or be untreatable with standard therapies.

Inclusion Criteria

I am fully active or have some restrictions but can still carry out light work.

Prior enfortumab vedotin specific requirements: Cohorts A1/A2/C: prior treatment with enfortumab vedotin is allowed, but not required. Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting. Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.

I have one of the listed types of cancer.

Exclusion Criteria

I have had issues with my cornea and a corneal transplant.

My diabetes is not under control.

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Dose Optimization (Phase 1a)

Participants receive escalating doses of LY4052031 to assess safety, tolerability, and pharmacokinetics, and determine the recommended phase 2 dose

21 days per cycle

Multiple visits per cycle (in-person)

Dose Expansion (Phase 1b)

Participants receive LY4052031 at the recommended phase 2 dose to evaluate efficacy and safety in expansion cohorts

Up to 48 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY4052031

Trial Overview The study tests LY4052031 to see if it's safe and works against different types of advanced cancers. It has two parts: first finding the right dose (phase Ia) and then seeing how well it works at that dose (phase Ib).

How Is the Trial Designed?

Group I: LY4052031 (Dose-optimization, Cohort A2) Experimental Treatment 1 Intervention

Comparing 2 or more doses (evaluated during dose escalation) of LY4052031 administered IV.

Group II: LY4052031 (Dose-expansion, Cohort B1, B2, C1) Experimental Treatment 1 Intervention

LY4052031 administered IV.

Group III: LY4052031 (Dose-escalation, Cohort A1) Experimental Treatment 1 Intervention

Escalating doses of LY4052031 administered intravenously (IV).

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana 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

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS900

NEXUS-01, a phase 1 study of LY4052031, an antibody ... LY4052031 has demonstrated robust in vivo efficacy in tumor models across a range of nectin-4 expression levels and in MMAE-resistance.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06465069

NCT06465069 | A Study of LY4052031 in Participants With ... The purpose of this study is to find out whether the study drug, LY4052031, is safe, tolerable and effective in participants with advanced, or metastatic solid ...

3. urotoday.com urotoday.com/clinical-trials/from-the-editor/157875-nectin-4-a-validated-target-for-urothelial-cancer-opening-the-door-for-novel-imaging-and-therapeutic-development.html

Nectin-4, A Validated Target for Urothelial Cancer The more recent FDA approval for enfortumab vedotin in combination with pembrolizumab on December 15, 20231 has yielded impressive results, ...

4. bcan.org bcan.org/clinicaltrials/ly4052031-in-participants-with-advanced-or-metastatic-urothelial-cancer-or-other-solid-tumors/

LY4052031 in Participants With Advanced or Metastatic ... The purpose of this study is to find out whether the study drug, LY4052031, is safe, tolerable and effective in participants with advanced, or metastatic solid ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.807

Phase I dose-escalation study of the next-generation nectin ... Results: Patients with metastatic urothelial cancer, cervical cancer, endometrial cancer, head and neck squamous cell carcinoma, non-small ...

6. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/LLY/pressreleases/34670226/eli-lillys-promising-study-on-ly4052031-for-advanced-cancers-a-potential-game-changer/

Eli Lilly's Promising Study on LY4052031 for Advanced ... The study aims to evaluate the safety, tolerability, and effectiveness of LY4052031 in patients with advanced or metastatic solid tumors, ...

7. asco.org asco.org/posters/POSTER242797

NEXUS-01, a phase 1 study of LY4052031, an antibody- ... The survival outcomes for men with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination deficiencies ...