LY3962673 for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+76 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Eli Lilly and Company
Disqualifiers: Active CNS metastases, Cardiovascular disease, Infections, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The main purpose of this study is to assess safety \& tolerability and antitumor activity of LY3962673 as monotherapy and in combination with other chemotherapy agents in participants with KRAS G12D-mutant advanced solid tumor types. The study is expected to last approximately 5 years.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What makes the drug LY3962673 unique for treating pancreatic cancer?
LY3962673 is unique because it is an oral drug that acts as a leukotriene B4 receptor antagonist and peroxisome proliferator-activated receptor gamma agonist, which can enhance the effectiveness of gemcitabine, a standard chemotherapy drug for pancreatic cancer, and is well tolerated.
12345Eligibility Criteria
This trial is for people with certain advanced solid tumors that have a specific mutation called KRAS G12D. Participants should be relatively active (ECOG ≤ 1), have had at least one prior chemotherapy treatment, and may join even if they have brain involvement as long as it's stable or treated.Inclusion Criteria
My cancer is advanced, cannot be surgically removed, and can be measured by specific criteria.
My cancer has the KRAS G12D mutation.
I am fully active and can carry on all pre-disease activities without restriction.
I have had at least one chemotherapy treatment for my advanced or metastatic disease.
Participant Groups
The study tests LY3962673 alone and combined with other chemo drugs like Gemcitabine and Cetuximab in treating cancers such as colorectal, lung, and pancreatic cancer. It aims to evaluate the safety, tolerability, and effectiveness of these treatments over about five years.
2Treatment groups
Experimental Treatment
Group I: Phase 1b: LY3962673 Dose ExpansionExperimental Treatment8 Interventions
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Group II: Phase 1a: LY3962673 Dose EscalationExperimental Treatment1 Intervention
Escalating doses of LY3962673 administered orally.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
UCLALos Angeles, CA
Sarah Cannon Research Institute at HealthOneDenver, CO
Florida Cancer Specialists Lake Nona Drug Development UnitOrlando, FL
Johns Hopkins HospitalBaltimore, MD
More Trial Locations
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Who is running the clinical trial?
Eli Lilly and CompanyLead Sponsor
Loxo Oncology, Inc.Industry Sponsor
References
Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas. [2022]LY293111 (LY) is a novel oral anticancer agent with leukotriene B4 receptor antagonist and peroxisome proliferator-activated receptor gamma agonist properties, producing promising results alone and in combination with gemcitabine in pancreatic cancer xenograft models. A phase I study proved that the combination (gemcitabine plus LY) is safe and well tolerated.
LY293111 improves efficacy of gemcitabine therapy on pancreatic cancer in a fluorescent orthotopic model in athymic mice. [2022]Pancreatic cancer has an abysmal prognosis because of late diagnosis and lack of effective therapeutics. New drugs are desperately needed. The present study determined the effect of the LTB4 receptor antagonist, LY293111, on tumor growth and metastases in a fluorescent orthotopic model of pancreatic cancer. Pancreatic cancer cells (S2-013) with stable expression of enhanced green fluorescent protein were implanted into the duodenal pancreatic lobe of athymic mice. Animals were allocated to four groups (eight mice per group): control (no treatment); LY293111; gemcitabine; and LY293111 + gemcitabine. Monitoring of the surgical procedure and follow-up examinations at 2, 3, and 4 weeks after implantation to monitor tumor growth and metastases were performed using a fluorescence microscope and the reversible skin-flap technique. A staging and scoring system was developed to evaluate tumor progression, based on the TNM classification. Control animals developed end-stage disease with invasive cancer, metastases, and cachexia. Tumor growth and incidence of metastases were significantly reduced in all treated mice. However, combined treatment with LY293111 and gemcitabine was most effective. LY293111 is a novel therapeutic agent for pancreatic cancer, which improves the efficacy of gemcitabine. It is well tolerated and can be administered orally and, therefore, provides a new hope for patients suffering from pancreatic adenocarcinoma.
Porous silicon nanocarriers for dual targeting tumor associated endothelial cells and macrophages in stroma of orthotopic human pancreatic cancers. [2021]Pancreatic cancer is a highly fatal disease characterized by a dominant stroma formation. Exploring new biological targets, specifically those overexpressed in stroma cells, holds significant potential for the design of specific nanocarriers to attain homing of therapeutic and imaging agents to the tumor. In clinical specimens of pancreatic cancer, we found increased expression of CD59 in tumor associated endothelial cells as well as infiltrating cells in the stroma as compared to uninvolved pancreas. We explored this dual targeting effect using orthotopic human pancreatic cancer in nude mice. By immunofluorescence analysis, we confirmed the increased expression of Ly6C, mouse homolog of CD59, in tumor associated endothelial cells as well as in macrophages within the stroma. We decorated the surface of porous silicon nanocarriers with Ly6C antibody. Targeted nanocarriers injected intravenously accumulated to tumor associated endothelial cells within 15min. At 4h after administration, 9.8±2.3% of injected dose/g tumor of the Ly6C targeting nanocarriers accumulated in the pancreatic tumors as opposed to 0.5±1.8% with non-targeted nanocarriers. These results suggest that Ly6C (or CD59) can serve as a novel dual target to deliver therapeutic agents to the stroma of pancreatic tumors.
Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. [2022]To determine the safety and efficacy of neoadjuvant gemcitabine/capecitabine followed by surgery for the treatment of locally advanced pancreatic adenocarcinoma (LAPC).
Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture. [2018]Commercially available, highly passaged pancreatic cancer (PC) cell lines are of limited translational value. Attempts to overcome this limitation have primarily consisted of cancer cell isolation and culture directly from human PC specimens. However, these techniques are associated with exceedingly low success rates. Here, we demonstrate a highly reproducible culture of primary PC cell lines (PPCLs) from patient-derived xenografts, which preserve, in part, the intratumoral heterogeneity known to exist in PC. PPCL expansion from patient-derived xenografts was successful in 100% of attempts (5 of 5). Phenotypic analysis was evaluated with flow cytometry, immunofluorescence microscopy, and short tandem repeat profiling. Importantly, tumorigenicity of PPCLs expanded from patient-derived xenografts was assessed by subcutaneous injection into nonobese diabeteic.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice. Morphologically, subcutaneous injection of all PPCLs into mice yielded tumors with similar characteristics to the parent xenograft. PPCLs uniformly expressed class I human leukocyte antigen, epithelial cell adhesion molecule, and cytokeratin-19. Heterogeneity within each PPCL persisted in culture for the frequency of cells expressing the cancer stem cell markers CD44, CD133, and c-Met and the immunologic markers human leukocyte antigen class II and programmed death ligand 1. This work therefore presents a reliable method for the rapid expansion of primary human PC cells and, thereby, provides a platform for translational investigation and, importantly, potential personalized therapeutic approaches.