Breast Neoplasms, Cholangiocarcinoma, Colorectal Neoplasms, Esophageal Neoplasms, Ovarian Neoplasms, Pancreatic Intraductal Neoplasms, Stomach Neoplasms
Conditions
Keywords
Cancer-associated fibroblasts (CAF), Lutetium-177, LuFAP, Lu-177-FAP
Brief summary
This is a study of LY4337713 in participants with certain types of cancer that is advanced or has spread. Participants must have cancer with high levels of a protein called fibroblast activation protein (FAP). The purpose of this study is to evaluate safety, side effects, and efficacy of LY4337713. In addition, this study will evaluate how much LY4337713 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. For each participant, the study will last about 5 years.
Interventions
DRUGLY4337713
Administered IV.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have clinical or imaging evidence of fibroblast activation protein (FAP) expression per local assessment * Must have histologically or cytologically confirmed diagnosis of one of the following: * Adenocarcinoma of the pancreas * Hormone receptor (HR)-positive human epidermal growth factor 2 (HER2)-negative breast cancer * HER2-positive breast cancer * Triple negative breast cancer (TNBC) * Platinum-resistant or refractory ovarian cancer (including ovarian carcinosarcoma) * Other solid tumors * Gastric cancer (adenocarcinoma) * Colorectal cancer (CRC) * Esophageal cancer (squamous cell carcinoma or adenocarcinoma) * Cholangiocarcinoma * Must have received prior treatments as indicated below: * Phase 1a * Adenocarcinoma of the pancreas: Participants must have received at least 1, but no more than 2 prior regimens for locally advanced unresectable or metastatic disease. * HR-positive HER2-negative breast cancer: Participants must have received less than or equal to (≤)5 prior lines of treatment for advanced or metastatic disease, which must include a cyclin-dependent kinase 4/6 inhibitor. * HER2-positive breast cancer: Participants must have received at least 2 lines of HER2-targeted therapy, which should include at least 1 antibody-drug conjugate (ADC) for metastatic disease (if locally available). * TNBC: Participants must have received at least 2 lines of therapy for metastatic disease. * Platinum-resistant or refractory ovarian cancer: Participants must have received or after at least 1 platinum-based therapy. * Other solid tumors (gastric cancer, CRC, esophageal and cholangiocarcinoma): Participants must have received greater than or equal to (≥)1 prior line of systemic therapy for advanced or metastatic disease; including prior line(s) in combination with immunotherapy or vascular endothelial growth factor inhibitor. * Phase 1b: * Participants must have advanced or metastatic solid tumors and have received ≥1 prior line of therapy. * Must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1. * Measured creatinine clearance ≥60 milliliters per minute (mL/min)
Exclusion criteria
* Have known active central nervous system (CNS) metastases or carcinomatous meningitis. * Have significant cardiovascular disease * Have prolongation of the corrected QTcF \>470 milliseconds (msec) during screening. QTcF is calculated using Fridericia's Formula: QTcF = QT/(RR0.33) * Have evidence of ongoing and untreated urinary tract obstruction * Had previous hemi- or total-body radiation. * Had previous adoptive T-cell therapy (e.g., chimeric antigen receptor T-cell \[CAR-T therapy, T-cell receptor \[TCR\] therapy, etc.) * Unable to lie flat during, or otherwise tolerate, single photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT) or magnetic resonance imaging (MRI).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR) | Baseline through imaging follow-up, up to 5 years | Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) |
| Phase 1a: Percentage of Participants with Dose Limited Toxicity (DLT) Toxicities | Cycle 1 (28 days) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY4337713 | Cycle 1 Day 1 up to Cycle 2 Day 4 post dose (Cycle = 4 or 6 weeks) | — |
| Phase 1a: PK: Area Under the Concentration Time Curve (AUC) of LY4337713 | Cycle 1 Day 1 up to Cycle 2 Day 4 post dose (Cycle = 4 or 6 weeks) | — |
| Phase 1a: Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR) | Baseline through imaging follow-up, up to 1 year | Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| Phase 1a: Number of Participants with Best Overall Response (BOR) | Baseline through imaging follow-up, up to 1 year | Best response recorded from the start of study treatment until the earliest of objective disease progression or start of new anticancer therapy, per RECIST v1.1. |
| Phase 1a and 1b: Duration of Response (DOR) | Baseline through imaging follow-up, up to 5 years | Time between the date of first documented response of CR or PR to the date of first disease progression, as assessed by the investigator per RECIST v1.1 or death due to any cause, whichever occurs first. |
| Phase 1a and 1b: Time to Response (TTR) | Baseline through imaging follow-up, up to 1 year | Time from first dose date to the date of first documented response of CR or PR |
| Phase 1a and 1b: Percentage of Participants with Disease Control Rate (DCR) | Baseline through imaging follow-up, up to 1 year | Percentage participants who achieved a BOR of CR, PR, or stable disease (SD), per RECIST v1.1 |
| Phase 1a: Absorbed Dose Estimates (Gy) in Normal Organs | Baseline through Cycle 4 Day 4 (Cycle = 4 or 6 weeks) | — |
Countries
China, Germany, Japan, Netherlands, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 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)
Eli Lilly and Company
Outcome results
None listed