Carcinoma, Non-Small-Cell LungPhase 1NCT07046923
A Study of LY4175408 in Participants With Advanced Cancer
A Phase 1 study testing LY4175408, Pembrolizumab and Carboplatin in people with Carcinoma, Non-Small-Cell Lung and Small Cell Lung Carcinoma, run by Eli Lilly and Company at 27 sites in 6 countries.
Trial summary
The purpose of this study is to measure the safety and efficacy of LY4175408 in participants with selected advanced cancer. In addition, this study will evaluate how much LY4175408 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. Participation could last up to 4 years. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Endometrial Neoplasms
- What is being tested?
- LY4175408, Pembrolizumab and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 27 sitesin 6 countries
- Study dates
- 28 Jul 2025to Jul 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 advanced or metastatic solid tumor cancers:
- Non-small cell lung cancer (NSCLC)
- Small cell lung cancer (SCLC)
- Endometrial cancer
- Triple negative breast cancer (TNBC) (characterized by HR-negative disease and HER2-negative expression according to American Society of Clinical Oncology (ASCO) - College of American Pathologists guidelines).
- Received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating investigator (except in Cohort B1 and B2 expansion, which require participants who are treatment naive in the advanced metastatic setting); OR the individual is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease.
Show all 9Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to (≤) 1.
- For dose optimization/dose and expansion cohorts (Cohort A2, Cohort B/C): Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Cohorts B1/B2: NSCLC with no known actionable genomic alterations. ≤2 prior lines of systemic therapy for advanced or metastatic disease in safety lead-in; no prior systemic therapy in expansion
Who cannot join
- Prior treatment with a protein tyrosine kinase 7 (PTK7) antibody-drug conjugate (ADC) with a topoisomerase I inhibitor as payload (prior therapy with a PTK7 ADC with a non-topoisomerase I inhibitor payload OR non-PTK7 ADC with any payload is permitted). Prior topoisomerase I-based ADCs are not allowed in cohorts A2, B1 or B2.
- Any serious unresolved toxicities from prior therapy.
- Individual with known or suspected history of uncontrolled central nervous system (CNS) metastases.
- Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection.
- Significant cardiovascular disease.
- Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 milliseconds (ms)
- History of pneumonitis/interstitial lung disease.
- Individuals who are pregnant, breastfeeding, or plan to breastfeed during the trial or within 30 days of the last dose of trial intervention.
Trial locations and contacts
27 sites in 6 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
27 sites in 6 countries
United States15 sites, 15 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
The University of Chicago Medical Center (UCMC)
Chicago, Illinois, 60637
- Recruiting
The Ohio State University (OSU) Wexner Medical Center
Columbus, Ohio, 43210
- Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
- Recruiting
John Theurer Cancer Center At Hackensack UMC
Hackensack, New Jersey, 07601
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Community Health Network
Indianapolis, Indiana, 46250
- Recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
- Recruiting
Columbia University
New York, New York, 10032
- Recruiting
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute
Orlando, Florida, 32827
- Recruiting
Florida Cancer Specialists - Sarasota
Sarasota, Florida, 34236
- Recruiting
Washington University
St Louis, Missouri, 63110
- Recruiting
Stanford Medicine Cancer Center
Stanford, California, 94305
- Recruiting
START Mountain Region
West Valley City, Utah, 84119
China3 sites, 3 recruiting
- Not yet recruiting
West China Hospital, Sichuan University
Chengdu, 610041
- Not yet recruiting
Shanghai East Hospital, Tongji University
Shanghai, 0200120
- Not yet recruiting
Tongji Hospital - Tongji Medical College of HUST
Wuhan, 430030
Japan3 sites, 3 recruiting
- Recruiting
Kyoto University Hospital
Kyoto, 606-8507
- Recruiting
National Cancer Center Hospital
Tokyo, 104-0045
- Recruiting
Cancer Institute Hospital of JFCR
Tokyo, 135-8550
France2 sites, 2 recruiting
- Recruiting
Centre Leon Berard
Lyon, 69373
- Recruiting
Institut Gustave Roussy
Villejuif, 94805
South Korea2 sites, 2 recruiting
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul, 03722
- Recruiting
Samsung Medical Center
Seoul, 06351
Spain2 sites, 2 recruiting
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
About this study
Official title: A First-in-Human, Phase 1a/1b Trial to Assess the Safety, Tolerability and Preliminary Efficacy of LY4175408, an Antibody Drug Conjugate Targeting Protein Tyrosine Kinase 7-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors
The purpose of this study is to measure the safety and efficacy of LY4175408 in participants with selected advanced cancer. In addition, this study will evaluate how much LY4175408 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. Participation could last up to 4 years.
- Conditions
- Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Endometrial Neoplasms, Neoplasm Metastasis, Triple Negative Breast Cancer
- Being tested
- LY4175408, Pembrolizumab, Carboplatin, Cisplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Endometrial Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY4175408Drug
IV infusion
PembrolizumabDrug
IV infusion
CarboplatinDrug
IV infusion
CisplatinDrug
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a Dose Escalation (Cohort A1) | Experimental | Escalating doses of LY4175408 administered intravenously (IV) Receives: Drug: LY4175408 |
| Phase 1a Dose Optimization (Cohort A2) | Experimental | Two or more doses of LY4175408 (evaluated during dose escalation) administered IV Receives: Drug: LY4175408 |
| Phase 1b Dose Expansion (Cohort B1) | Experimental | LY4175408 administered IV followed by pembrolizumab administered IV Receives: Drug: LY4175408; Drug: Pembrolizumab |
| Phase 1b Dose Expansion (Cohort B2) | Experimental | LY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV Receives: Drug: LY4175408; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin |
| Phase 1b Dose Expansion (Cohorts C1, C2 and C3) | Experimental | LY4175408 administered IV Receives: Drug: LY4175408 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408
Measured: 1 Cycle (21 days)
Phase 1b-Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)
Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Measured: Baseline up to approximately 4 years
Secondary outcomes (7)
Phase 1a and 1b-Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of LY4175408 (total antibody, conjugated antibody, free payload)
Measured: First 4 cycles (84 days)
Phase 1a and 1b-PK: Area under the Concentration versus Time Curve (AUC) of LY4175408 (total antibody, conjugated antibody, free payload)
Measured: First 4 cycles (84 days)
Phase 1a-ORR: Percentage of Participants with Best Response of CR or PR
Per investigator assessed RECIST 1.1
Measured: Baseline up to approximately 4 years
Phase 1a and 1b-Time to Response (TTR)
Per investigator assessed RECIST 1.1
Measured: Baseline up to approximately 4 years
Phase 1a and 1b-Progression-free Survival (PFS)
Per investigator assessed RECIST 1.1
Measured: Baseline up to approximately 4 years
Phase 1a and 1b-Disease Control Rate (DCR)
Per investigator assessed RECIST 1.1
Measured: Baseline up to approximately 4 years
Phase 1a and 1b-Duration of Response (DOR)
Per investigator assessed RECIST 1.1
Measured: Baseline up to approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2025
- Study start28 Jul 2025
- Primary completionJul 2030 (estimated)
- Study completionJul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 240 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
- NCT07046923
- Sponsor's protocol ID
- 27401
- Other IDs
- J6D-MC-JSDA, 2025-521916-20-00, 2025
- Status last verified
- Jun 2026
- First submitted
- 24 Jun 2025
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in-Human, Phase 1a/1b Trial to Assess the Safety, Tolerability and Preliminary Efficacy of LY4175408, an Antibody Drug Conjugate Targeting Protein Tyrosine Kinase 7-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT07046923
- Acronym / sponsor ID
- 27401
- Conditions
- Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Endometrial Neoplasms, Neoplasm Metastasis, Triple Negative Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 28 Jul 2025 (actual)
- Primary completion
- Jul 2030 (estimated)
- Study completion
- Jul 2030 (estimated)
- First posted
- 2 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to measure the safety and efficacy of LY4175408 in participants with selected advanced cancer. In addition, this study will evaluate how much LY4175408 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. Participation could last up to 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase 1a Dose Escalation (Cohort A1) | Experimental | Drug: LY4175408Escalating doses of LY4175408 administered intravenously (IV) |
| Phase 1a Dose Optimization (Cohort A2) | Experimental | Drug: LY4175408Two or more doses of LY4175408 (evaluated during dose escalation) administered IV |
| Phase 1b Dose Expansion (Cohort B1) | Experimental | Drug: LY4175408, Drug: PembrolizumabLY4175408 administered IV followed by pembrolizumab administered IV |
| Phase 1b Dose Expansion (Cohort B2) | Experimental | Drug: LY4175408, Drug: Pembrolizumab, Drug: Carboplatin, Drug: CisplatinLY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV |
| Phase 1b Dose Expansion (Cohorts C1, C2 and C3) | Experimental | Drug: LY4175408LY4175408 administered IV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Have one of the following advanced or metastatic solid tumor cancers:
- Received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating investigator (except in Cohort B1 and B2 expansion, which require participants who are treatment naive in the advanced metastatic setting); OR the individual is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to (≤) 1.
- For dose optimization/dose and expansion cohorts (Cohort A2, Cohort B/C): Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Cohorts B1/B2: NSCLC with no known actionable genomic alterations. ≤2 prior lines of systemic therapy for advanced or metastatic disease in safety lead-in; no prior systemic therapy in expansion
Key exclusion criteria (8 listed)
- Prior treatment with a protein tyrosine kinase 7 (PTK7) antibody-drug conjugate (ADC) with a topoisomerase I inhibitor as payload (prior therapy with a PTK7 ADC with a non-topoisomerase I inhibitor payload OR non-PTK7 ADC with any payload is permitted). Prior topoisomerase I-based ADCs are not allowed in cohorts A2, B1 or B2.
- Any serious unresolved toxicities from prior therapy.
- Individual with known or suspected history of uncontrolled central nervous system (CNS) metastases.
- Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection.
- Significant cardiovascular disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY4175408IV infusion | Drug | Phase 1a Dose Escalation (Cohort A1), Phase 1a Dose Optimization (Cohort A2), Phase 1b Dose Expansion (Cohort B1), Phase 1b Dose Expansion (Cohort B2), Phase 1b Dose Expansion (Cohorts C1, C2 and C3) |
| PembrolizumabIV infusion | Drug | Phase 1b Dose Expansion (Cohort B1), Phase 1b Dose Expansion (Cohort B2) |
| CarboplatinIV infusion | Drug | Phase 1b Dose Expansion (Cohort B2) |
| CisplatinIV infusion | Drug | Phase 1b Dose Expansion (Cohort B2) |
Primary outcome
Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408
Time frame: 1 Cycle (21 days)
Phase 1b-Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)
Time frame: Baseline up to approximately 4 years
Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
7 secondary outcomes
Phase 1a and 1b-Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of LY4175408 (total antibody, conjugated antibody, free payload)
Time frame: First 4 cycles (84 days)
Phase 1a and 1b-PK: Area under the Concentration versus Time Curve (AUC) of LY4175408 (total antibody, conjugated antibody, free payload)
Time frame: First 4 cycles (84 days)
Phase 1a-ORR: Percentage of Participants with Best Response of CR or PR
Time frame: Baseline up to approximately 4 years
Phase 1a and 1b-Time to Response (TTR)
Time frame: Baseline up to approximately 4 years
Phase 1a and 1b-Progression-free Survival (PFS)
Time frame: Baseline up to approximately 4 years
Phase 1a and 1b-Disease Control Rate (DCR)
Time frame: Baseline up to approximately 4 years
Phase 1a and 1b-Duration of Response (DOR)
Time frame: Baseline up to approximately 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- A Study of LY4175408 in Participants With Advanced CancerLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Carcinoma, Non-Small-Cell Lung
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or contact
Physicians interested in becoming principal investigators please contact contact
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
27 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY4175408, Pembrolizumab and Carboplatin in people with Carcinoma, Non-Small-Cell Lung and Small Cell Lung Carcinoma, run by Eli Lilly and Company at 27 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, China, Japan, France, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or (1-317-615-4559, LillyTrials@Lilly.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408 (time frame: 1 Cycle (21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.