Metastatic Solid TumorPhase 1NEXUS-01NCT06465069
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
A Phase 1 study testing LY4052031 and Pembrolizumab in people with Metastatic Solid Tumor and Recurrent Solid Tumor, run by Eli Lilly and Company at 39 sites in 8 countries.
Trial summary
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 tumors including urothelial cancer. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Solid Tumor, Recurrent Solid Tumor, Advanced Solid Tumor
- What is being tested?
- LY4052031 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 460 participants
- Where
- 39 sitesin 8 countries
- Study dates
- 1 Jul 2024to May 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have one of the following solid tumor cancers:
- Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
- Cohort A2/B/D: urothelial carcinoma
- Cohort C: triple negative breast cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, HNSCC (head and neck squamous cell carcinoma), esophageal cancer, pancreatic cancer, or prostate cancer
- Prior Systemic Therapy Criteria:
- Cohort A1/C: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
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- Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
- Cohort D: Treatment-naive for locally advanced or metastatic urothelial cancer.
- Prior enfortumab vedotin specific requirements:
- Cohorts A1/A2/C/D: 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.
- Measurability of disease
- Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
- Measurable disease is required as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) for all Cohorts. Cohort A1 may permit non-measurable disease as defined by RECIST v1.1
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations
Who cannot join
- Individual with known or suspected uncontrolled CNS metastases
- Individual with uncontrolled hypercalcemia
- Individual with uncontrolled diabetes
- Individual with evidence of corneal keratopathy or keratitis, and history of corneal transplant
- Any serious unresolved toxicities from prior therapy
- Significant cardiovascular disease
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- Recent thromboembolic event and/or clinically significant bleeding disorder
- Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
- History of pneumonitis/interstitial lung disease
- History of Grade ≥3 skin toxicity associated with enfortumab vedotin that required treatment discontinuation
- Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
Trial locations and contacts
39 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or contact
Physicians interested in becoming principal investigators please contact contact
39 sites in 8 countries
United States22 sites, 21 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02215
- Recruiting
University of Chicago Hospital
Chicago, Illinois, 60637
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
- Recruiting
Sarah Cannon Research Institute at HealthOne
Denver, Colorado, 80218
- Recruiting
City of Hope National Medical Center
Duarte, California, 91010-0269
- Recruiting
START Midwest Cancer and Hematology Centers of W Michigan
Grand Rapids, Michigan, 49546
- Recruiting
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4000
- Not yet recruiting
IU Simon Cancer Center
Indianapolis, Indiana, 46202
- Recruiting
University of California, San Diego (UCSD) - Moores Cancer Center
La Jolla, California, 92093
- Recruiting
UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California, 90024
- Recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
- Not yet recruiting
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
- Recruiting
NYU Langone Medical Center - Perlmutter Cancer Center (NYU Cancer Institute)
New York, New York, 10016
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029-6574
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10032-3729
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
University of Utah - Huntsman Cancer Institute
Salt Lake City, Utah, 84112
- Recruiting
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229
- Recruiting
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
- Completed
Florida Cancer Specialists and Research Institute
St. Petersburg, Florida, 33705
- Recruiting
START Mountain Region
West Valley City, Utah, 84119
Japan4 sites, 4 recruiting
- Recruiting
National Cancer Center Hospital
Chūōku, 104-0045
- Recruiting
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
- Recruiting
The Cancer Institute Hospital of JFCR
Kōtō City, 135-8550
- Recruiting
Aichi Cancer Center Hospital
Nagoya, 464-8681
Spain4 sites, 4 recruiting
- Recruiting
Catalan Institute of Oncology Duran i Reynals Hospital
Barcelona, 8908
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
- Recruiting
Hospital Madrid Norte Sanchinarro
Madrid, 28050
- Recruiting
Hospital Universitario Virgen Del Rocio
Seville, 41013
China3 sites, 3 recruiting
- Recruiting
Beijing Cancer hospital
Beijing, 100142
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, 510060
- Recruiting
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, 200000
Australia2 sites, 2 recruiting
- Recruiting
St Vincent's Hospital
Darlinghurst, 2010
- Recruiting
Linear Clinical Research
Nedlands, 6009
United Kingdom2 sites, 2 recruiting
- Recruiting
St Bartholomew's Hospital
London, EC1A 7BE
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
France1 site, 1 recruiting
- Recruiting
Institut Gustave Roussy (Igr)
Villejuif, 94805
South Korea1 site, 1 recruiting
- Recruiting
Asan Medical Center
Seoul, 05505
About this study
Official title: A Phase 1a/1b Study of LY4052031, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Advanced or Metastatic Urothelial Carcinoma or Other Solid Tumors
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 tumors including urothelial cancer. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
Read the detailed description
This is a Phase 1a/1b multicenter, open-label study in participants with advanced or metastatic solid tumor malignancies known to express Nectin 4. This study evaluates an antibody-drug conjugate that binds to the protein nectin-4, which is expressed on certain cancer cells, delivering the drug to the cancer. This study is comprised of two phases: Dose Escalation and Dose Optimization (1a), and Dose expansion (1b). Phase 1a will assess the safety, tolerability, and pharmacokinetics of LY4052031 to determine the recommended phase 2 dose (RP2D)/optimal dose. Phase 1b will evaluate efficacy and safety of LY4052031 as monotherapy or in combination with pembrolizumab at the RP2D/optimal dose in expansion cohorts based on tumor type and/or treatment history.
- Conditions
- Metastatic Solid Tumor, Recurrent Solid Tumor, Advanced Solid Tumor, Urinary Bladder Neoplasm, Triple Negative Breast Cancer, Non-small Cell Lung Cancer
- Being tested
- LY4052031, Pembrolizumab
- Keywords
- Bladder Cancer, Bladder Neoplasm, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Urothelial Neoplasms, Renal Pelvis Cancer, Ureter Cancer, Nectin-4, Antibody Drug Conjugate (ADC), Triple Negative Breast Cancer (TNBC), Non-small Cell Lung Cancer (NSCLC), Head and Neck Squamous Cell Carcinoma (HNSCC)
- Medical subject headings
- Neoplasm Metastasis, Urinary Bladder Neoplasms, Triple Negative Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Esophageal Neoplasms, Pancreatic Neoplasms, Ovarian Neoplasms, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY4052031Drug
Intravenous
PembrolizumabDrug
Intravenous
| Study group | Role | What they receive |
|---|---|---|
| LY4052031 (Dose-escalation, Cohort A1) | Experimental | Escalating doses of LY4052031 administered intravenously (IV). Receives: Drug: LY4052031 |
| LY4052031 (Dose-optimization, Cohort A2) | Experimental | Comparing 2 or more doses (evaluated during dose escalation) of LY4052031 administered IV. Receives: Drug: LY4052031 |
| LY4052031 (Dose-expansion, Cohort B1, B2, C1) | Experimental | LY4052031 administered IV. Receives: Drug: LY4052031 |
| LY4052031+ Pembrolizumab (Dose-expansion, Cohort D) | Experimental | LY4052031 administered IV. Pembrolizumab administered IV. Receives: Drug: LY4052031; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1a: To determine the recommended phase 2 dose (RP2D) optimal dose(s) of LY4052031
Number of participants with dose-limiting toxicities (DLTs)
Measured: Cycle 1 (21 Days)
Phase 1b: To assess the antitumor activity of LY4052031 as monotherapy or in combination with pembrolizumab: Overall response rate (ORR)
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Measured: Up to Approximately 48 Months or 4 Years
Secondary outcomes (8)
To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin)
PK: Cmin of LY4052031
Measured: Cycle 1 (21 Days)
To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC)
PK: AUC of LY4052031
Measured: Cycle 1 (21 Days)
To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Overall response rate (ORR)
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1))
Measured: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Duration of response (DOR)
DOR per investigator assessed RECIST 1.1
Measured: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Time to response (TTR)
TTR per investigator assessed RECIST 1.1
Measured: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Progression free survival (PFS)
PFS per investigator assessed RECIST 1.1
Measured: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Disease control rate (DCR)
DCR per investigator assessed RECIST 1.1
Measured: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Overall survival (OS)
OS per investigator assessed RECIST 1.1
Measured: Up to Approximately 48 Months or 4 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2024
- Study start1 Jul 2024
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Solid TumorStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06465069
- Sponsor's protocol ID
- 18882
- Other IDs
- 2024-512927-36-00, J5I-OX-JZYA, LOXO-LNC-24001
- Acronym
- NEXUS-01
- Status last verified
- Oct 2026
- First submitted
- 13 Jun 2024
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No