LY3962673 for Pancreatic Cancer

(MOONRAY-01 Trial)

Recruiting at 85 trial locations

Overseen By There may be multiple sites in this clinical trial. (Add "This 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Disqualifiers: Active CNS metastases, Cardiovascular disease, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

570 Participants Needed

What You Need to Know Before You Apply

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. ^{1 2 3 4 5}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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.

I have brain involvement that is either symptom-free or has been treated.

My cancer has the KRAS G12D mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a: Dose Escalation

Escalating doses of LY3962673 administered orally to assess safety and tolerability

Up to approximately 5 years

Phase 1b: Dose Expansion

LY3962673 administered orally either alone or in combination with other chemotherapy agents to assess antitumor activity

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3962673

Trial Overview 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.

How Is the Trial Designed?

Group I: Phase 1b: LY3962673 Dose Expansion Experimental Treatment 8 Interventions

LY3962673 administered orally either alone or in combination with other chemotherapy agents.

Group II: Phase 1a: LY3962673 Dose Escalation Experimental Treatment 1 Intervention

Escalating doses of LY3962673 administered orally.

Group III: Experimental: Phase 1a: LY3962673 Monotherapy Experimental Treatment 1 Intervention

LY3962673 administered orally

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Loxo Oncology, Inc.

Industry Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Published Research Related to This Trial

In a phase I study, the combination of the novel anticancer agent LY293111 (LY) with gemcitabine was found to be safe and well tolerated in patients with advanced pancreatic cancer.

However, in a randomized trial involving chemotherapy-naive patients, adding LY to gemcitabine did not improve six-month survival, progression-free survival, or response rates, and was associated with a trend towards increased severe diarrhea without increasing hematologic toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas. Saif, MW., Oettle, H., Vervenne, WL., et al.[2022]

The LTB4 receptor antagonist LY293111 significantly reduced tumor growth and metastases in a mouse model of pancreatic cancer, showing promise as a new therapeutic option.

When combined with the standard chemotherapy drug gemcitabine, LY293111 enhanced treatment efficacy, suggesting a potential for improved outcomes in patients with pancreatic adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY293111 improves efficacy of gemcitabine therapy on pancreatic cancer in a fluorescent orthotopic model in athymic mice. Hennig, R., Ventura, J., Segersvard, R., et al.[2022]

Increased expression of CD59 in pancreatic cancer stroma and endothelial cells presents a promising target for delivering therapies specifically to tumors, as shown in clinical specimens.

Targeted nanocarriers decorated with Ly6C antibodies demonstrated significantly higher accumulation in pancreatic tumors (9.8% of injected dose/g tumor) compared to non-targeted carriers (0.5%), indicating effective dual targeting for therapeutic delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Porous silicon nanocarriers for dual targeting tumor associated endothelial cells and macrophages in stroma of orthotopic human pancreatic cancers. Yokoi, K., Godin, B., Oborn, CJ., et al.[2021]

In a study of 43 patients with locally advanced pancreatic adenocarcinoma, neoadjuvant chemotherapy with gemcitabine/capecitabine allowed for curative surgery in 39.5% of cases, with a 32.5% rate of achieving complete tumor resection (R0).

Patients who underwent surgery had a median overall survival of 23.1 months, significantly longer than the 13.2 months for those who could not have surgery, indicating that neoadjuvant chemotherapy may improve survival outcomes for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Lee, JL., Kim, SC., Kim, JH., et al.[2022]

A new method successfully cultured primary pancreatic cancer cell lines (PPCLs) from patient-derived xenografts, achieving a 100% success rate in expanding these cells, which helps preserve the tumor's original characteristics.

The PPCLs maintained intratumoral heterogeneity and expressed key cancer and immune markers, making them a valuable tool for personalized therapy research and better understanding of pancreatic cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture. Pham, K., Delitto, D., Knowlton, AE., et al.[2018]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

LY293111 improves efficacy of gemcitabine therapy on pancreatic cancer in a fluorescent orthotopic model in athymic mice. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Porous silicon nanocarriers for dual targeting tumor associated endothelial cells and macrophages in stroma of orthotopic human pancreatic cancers. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture. [2018]