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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06238479




Registration number
NCT06238479
Ethics application status
Date submitted
26/01/2024
Date registered
2/02/2024
Date last updated
18/06/2024

Titles & IDs
Public title
A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors
Scientific title
A Phase 1 Trial Investigating LY4101174, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Recurrent, Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
J5A-OX-JZWA
Secondary ID [2] 0 0
LOXO-ENC-23001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Solid Tumor 0 0
Recurrent Solid Tumor 0 0
Advanced Solid Tumor 0 0
Urinary Bladder Neoplasm 0 0
Triple Negative Breast Cancer 0 0
Non-small Cell Lung Cancer 0 0
Esophageal Cancer 0 0
Pancreatic Cancer 0 0
Ovarian Cancer 0 0
Cervical Cancer 0 0
Head and Neck Squamous Cell Carcinoma 0 0
Prostate Cancer 0 0
Renal Pelvis Cancer 0 0
Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Other cancer types
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY4101174

Experimental: LY4101174 (Dose-escalation, Cohort A1) - Escalating doses of LY4101174 administered intravenously (IV).

Experimental: LY4101174 (Dose-optimization, Cohort A2) - Comparing 2 or more doses (evaluated during dose escalation) of LY4101174 administered IV.

Experimental: LY4101174 (Dose-expansion, Cohort B1, B2, C1-C5)) - LY4101174 administered IV.


Treatment: Drugs: LY4101174
Intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: To determine the recommended dose of LY4101174
Timepoint [1] 0 0
First 2 Cycles (28 days)
Primary outcome [2] 0 0
Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4101174
Timepoint [2] 0 0
First 2 Cycles (28 days)
Primary outcome [3] 0 0
Phase 1b: To assess the antitumor activity of LY4101174 Monotherapy: Overall response rate (ORR)
Timepoint [3] 0 0
Up to Approximately 48 Months or 4 Years
Secondary outcome [1] 0 0
To characterize the pharmacokinetics (PK) properties of LY4101174: Minimum Plasma Concentration (Cmin)
Timepoint [1] 0 0
Cycle 1 (14 Days)
Secondary outcome [2] 0 0
To characterize the PK properties of LY4101174: Area under the concentration versus time curve (AUC)
Timepoint [2] 0 0
Cycle 1 (14 Days)
Secondary outcome [3] 0 0
To evaluate the preliminary antitumor activity of LY4101174: Overall response rate (ORR)
Timepoint [3] 0 0
Up to Approximately 48 Months or 4 Years
Secondary outcome [4] 0 0
To evaluate the preliminary antitumor activity of LY4101174: Duration of response (DOR)
Timepoint [4] 0 0
Up to Approximately 48 Months or 4 Years
Secondary outcome [5] 0 0
To evaluate the preliminary antitumor activity of LY4101174: Time to response (TTR)
Timepoint [5] 0 0
Up to Approximately 48 Months or 4 Years
Secondary outcome [6] 0 0
To evaluate the preliminary antitumor activity of LY4101174: Progression free survival (PFS)
Timepoint [6] 0 0
Up to Approximately 48 Months or 4 Years
Secondary outcome [7] 0 0
To evaluate the preliminary antitumor activity of LY4101174: Disease control rate (DCR)
Timepoint [7] 0 0
Up to Approximately 48 Months or 4 Years
Secondary outcome [8] 0 0
To evaluate the preliminary antitumor activity of LY4101174: Overall survival (OS)
Timepoint [8] 0 0
Up to Approximately 48 Months or 4 Years

Eligibility
Key inclusion criteria
* 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/B1/B2: urothelial carcinoma
* Cohort C1: triple negative breast cancer
* Cohort C2: non-small cell lung cancer
* Cohort C3: ovarian or fallopian tube cancer
* Cohort C4: cervical cancer
* Cohort C5: head and neck squamous cell carcinoma
* Prior Systemic Therapy Criteria:

* Cohort A1/C1-5: 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
* 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.
* Prior enfortumab vedotin specific requirements:

* Cohorts A1/A2/C1-5: 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)
* Cohorts A2, B1, B2, C1-5: measurable disease required 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Current of history of intestinal obstruction in the previous 3 months
* Recent thromboembolic event or 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 when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/03/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/03/2027
Actual
Sample size
Target
280
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Icon Cancer Centre Kurralta Park - Kurralta Park
Recruitment postcode(s) [1] 0 0
5037 - Kurralta Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Japan
State/province [6] 0 0
Tokyo

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Loxo Oncology, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors. 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.
Trial website
https://clinicaltrials.gov/study/NCT06238479
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Xiaojian (Thomas) Xu
Address 0 0
Loxo Oncology, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patient Advocacy
Address 0 0
Country 0 0
Phone 0 0
855-569-6305
Fax 0 0
Email 0 0
clinicaltrials@loxooncology.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06238479