LY3962673 for Pancreatic Cancer

(MOONRAY-01 Trial)

Recruiting at 89 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

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

630 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, LY3962673, for individuals with advanced cancer, specifically those with a KRAS G12D mutation. The main goal is to assess the safety and effectiveness of LY3962673, both alone and in combination with other cancer drugs. Individuals who have undergone at least one prior round of chemotherapy and possess this specific tumor mutation may be suitable candidates. The study aims to determine if this treatment can successfully shrink tumors or slow their growth. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that LY3962673 is likely to be safe for humans?

Research shows that LY3962673 targets a specific change in certain cancer cells, known as KRAS G12D. Studies have demonstrated that this treatment is quite selective, focusing on attacking cancer cells while sparing normal cells. This selectivity is a positive sign for safety.

In early tests, researchers administered LY3962673 to patients with advanced solid tumors to assess patient tolerance. The main goal was to find a safe dose and identify any major side effects. Although detailed results are not yet available, its testing in humans indicates sufficient confidence in its safety to proceed.

Since this trial is in the early stages, the focus is on ensuring safety and determining the right dose. Researchers are still learning about possible side effects. Participants in these trials help researchers understand how the treatment works in humans and whether it causes any harm. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about LY3962673 for pancreatic cancer because it introduces a new approach compared to the standard treatments like chemotherapy and targeted therapies. Unlike these treatments, which often have significant side effects and varying efficacy, LY3962673 is administered orally and is being explored both as a monotherapy and in combination with other chemotherapy agents. This versatility in administration could potentially offer more personalized treatment options for patients. Additionally, the drug's novel mechanism of action might provide a fresh avenue for tackling pancreatic cancer, which is notoriously difficult to treat effectively with existing options.

What evidence suggests that LY3962673 might be an effective treatment for pancreatic cancer?

Research has shown that LY3962673 may help treat pancreatic cancer, particularly in cases with the KRAS G12D mutation. Studies have found that 30% of patients experienced tumor shrinkage with this treatment. In this trial, participants will receive LY3962673 either as a monotherapy or combined with other chemotherapy agents. Early results suggest that LY3962673 is more effective when used with other cancer drugs. The treatment has also shown few side effects, making it a potentially safer option. Overall, these findings are promising for those with advanced pancreatic cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

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)

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06586515

MOONRAY-01, A Study of LY3962673 in Participants With ... The main purpose of this study is to assess safety & tolerability and antitumor activity of LY3962673 as monotherapy and in combination with other chemotherapy ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/3316/739111/Abstract-3316-LY3962673-an-oral-highly-potent

Abstract 3316: LY3962673, an oral, highly potent, mutant ... LY3962673 also showed enhanced efficacy when combined with other anti-cancer agents. Taken together, the findings underscore the potential ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12352898/

KRAS: the Achilles' heel of pancreas cancer biology - PMC Early clinical evaluation showed promising efficacy in PDAC (30% ORR) with very limited toxicity (Table 3). Several additional OFF (LY3962673, ...

4. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473204

Treatment Innovations in Pancreatic Cancer Targeted approach and immunotherapies hold promise to improve outcomes for patients with advanced pancreatic cancer, but need to be tested in ...

5. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/pancreatic-ductal-adenocarcinoma

Pancreatic Ductal Adenocarcinoma clinical trials at UCLA The main purpose of this study is to assess safety & tolerability and antitumor activity of LY3962673 as monotherapy and in combination with ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS845

MOONRAY-01, a phase 1 study of LY3962673, a potent ... Key objectives are to determine the RP2D/optimal dose and assess the safety, tolerability, PK properties, and antitumor activity of LY3962673 ...

7. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_15327.moonray-01-a-study-of-ly3962673-in-participants-with-kras-g12d-mutant-solid-tumors-moonray-01.html

MOONRAY-01, A Study of LY3962673 in Participants With ... The main purpose of this study is to assess safety & tolerability and antitumor activity of LY3962673 as monotherapy and in combination with other chemotherapy ...

8. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/cancer/clinicaltrial/2653/phase-1a1b-trial-ly3962673/

A Phase 1a/1b Trial of LY3962673 in Participants with KRAS ... This study is testing the tolerability, effectiveness, and potential for few side effects of the drug LY3962673 in patients with advanced solid tumors that ...