LUNA18 for Solid Tumors

Recruiting at 18 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Chugai Pharmaceutical

Disqualifiers: Cardiovascular disease, CNS malignancy, ILD, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called LUNA18 to see if it can help treat advanced or spreading cancers. Researchers will look at how the drug moves through and affects the body, and whether it can help control or reduce tumors. The study includes patients whose cancer is difficult to treat with standard therapies.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the idea that LUNA18 for Solid Tumors is an effective treatment?

The available research does not provide specific data on the effectiveness of LUNA18 for Solid Tumors. The studies mentioned focus on other treatments and conditions, such as breast cancer and lung cancer, and do not include information about LUNA18. Therefore, there is no direct evidence from the provided information to support the effectiveness of LUNA18 for Solid Tumors. ^{1 2 3 4 5}

What safety data is available for LUNA18 treatment?

The safety data for LUNA18, which may be related to Aurora kinase inhibitors like MLN8237 (alisertib) and MK-0457, includes common side effects such as febrile neutropenia, stomatitis, gastrointestinal toxicity, hypertension, and fatigue. These side effects have been observed in clinical trials involving Aurora kinase inhibitors for advanced solid tumors. Specific studies, such as the Phase I study of MLN8237, evaluated safety, pharmacokinetics, and dose-limiting toxicities in patients with advanced solid tumors. ^{6 7 8 9 10}

Is the drug LUNA18 a promising treatment for solid tumors?

Yes, LUNA18 is a promising treatment for solid tumors. It has shown strong anti-tumor effects in animal studies, including reducing tumor growth and spreading. It also tends to stay in the tumor area, which could make it more effective. ^{11 12 13 14 15}

Research Team

Sponsor Chugai Pharmaceutical Co. Ltd

Principal Investigator

[e-mail]

Eligibility Criteria

Adults over 18 with advanced solid tumors not responding to standard treatments can join. They must be relatively healthy (ECOG status of 0 or 1) and have RAS mutation-positive tumors that are measurable. Those with serious heart conditions, uncontrolled diseases, lung complications like ILD, brain cancer, or active brain metastases needing treatment cannot participate.

Inclusion Criteria

I am 18 years old or older.

My cancer is advanced, cannot be cured with surgery, and standard treatments haven't worked or I can't tolerate them.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have any severe, uncontrolled illnesses like heart, lung, or kidney diseases.

I do not have serious heart problems like recent heart attacks or unstable heart rhythms.

I have a brain tumor or cancer spread to my brain that needs treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients receive LUNA18 capsule(s) at escalated doses to determine safety and tolerability

6-9 days for Cycle 0, 28 days for Cycle 1

Cohort Expansion

Patients receive LUNA18 capsule(s) at the recommended dose, alone or in combination with cetuximab

Up to approximately 43 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LUNA18 (Other)

Trial Overview The study is testing LUNA18's safety and effectiveness alone or with other cancer drugs in patients with advanced solid tumors. It's a Phase 1 trial where doses increase gradually to find the right balance between safety and potential benefits.

Participant Groups

Group I: Dose finding part (Part D) Experimental Treatment 2 Interventions

Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses

Group II: Dose escalation part (Part A) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at escalated doses

Group III: Cohort expansion part (Part E) Experimental Treatment 2 Interventions

Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose

Group IV: Cohort expansion part (Part C) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at the recommended dose

Group V: Biomarker part (Part B) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A

Group VI: Backfill part (Part AA) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A

Who Is Running the Clinical Trial?

Chugai Pharmaceutical

Lead Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Findings from Research

Between 2017 and 2021, the FDA approved 161 new therapeutic agents for solid tumors, marking a significant increase in treatment options for cancer patients.

However, only 27% of these approvals demonstrated clear evidence of improving overall survival, with many relying on surrogate endpoints, indicating a need for better quality and assurance of clinical benefits in new cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An appraisal of FDA approvals for adult solid tumours in 2017-2021: has the eagle landed? Cherny, NI.[2022]

In a review of 14 trials involving 12,567 patients with advanced non-small-cell lung cancer (NSCLC), a strong association was found between overall response rate (ORR) and progression-free survival (PFS), indicating that treatments that improve ORR likely also enhance PFS.

However, no significant association was observed between ORR and overall survival (OS), suggesting that while responders have better PFS and OS, factors like treatment cross-over and prolonged survival after disease progression may complicate the relationship between these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. Blumenthal, GM., Karuri, SW., Zhang, H., et al.[2022]

In a study of 12,081 women with stage I-IIIa, node-negative, hormone receptor-positive breast cancer, Oncotype DX recurrence scores were found to be similarly received by both non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients, indicating equitable access to testing.

Despite comparable testing, NHB women with low recurrence scores had a significantly higher risk of breast cancer mortality compared to NHW women, suggesting that factors beyond the Oncotype DX scores may contribute to racial disparities in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncotype DX recurrence score implications for disparities in chemotherapy and breast cancer mortality in Georgia. Collin, LJ., Yan, M., Jiang, R., et al.[2023]

A study comparing real-world outcomes of 107 women with metastatic breast cancer receiving letrozole to 222 women in the PALOMA-2 trial found similar median progression-free survival rates (18.4 months vs. 16.6 months), suggesting that real-world data can effectively reflect clinical trial results.

Response rates were also comparable between the two groups (41.8% in the real-world cohort vs. 39.4% in PALOMA-2), indicating that electronic health record data can provide reliable insights into treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer. Huang Bartlett, C., Mardekian, J., Cotter, MJ., et al.[2020]

In a phase 2 trial involving 125 patients with recurrent/metastatic head and neck squamous-cell carcinoma, the combination of palbociclib and cetuximab did not significantly improve overall survival compared to placebo and cetuximab, with median overall survival times of 9.7 months and 7.8 months respectively.

The most common side effects associated with palbociclib were rash and neutropenia, indicating that while the treatment was generally tolerated, it did come with notable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial. Adkins, DR., Lin, JC., Sacco, A., et al.[2021]

The phase I study of MLN8237 (alisertib) in 87 adult patients with advanced solid tumors demonstrated that the drug is generally well-tolerated, with common side effects including fatigue, nausea, and neutropenia.

At the maximum tolerated dose of 50 mg twice daily, MLN8237 effectively inhibited Aurora A kinase activity, leading to a partial response in 1% of patients and stable disease in 23% for at least 3 months, suggesting potential efficacy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Dees, EC., Cohen, RB., von Mehren, M., et al.[2021]

Aurora kinase inhibitors, targeting Aurora A and B, have shown promising anti-tumor activity in clinical trials, particularly in advanced cancers like ovarian cancer and acute myelogenous leukemia.

While these inhibitors can lead to significant responses, including complete remissions, they are also associated with notable side effects such as febrile neutropenia, gastrointestinal toxicity, and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress. Falchook, GS., Bastida, CC., Kurzrock, R.[2022]

The maximum-tolerated dose (MTD) of MK-0457, a novel pan-Aurora kinase inhibitor, was determined to be 64 mg/m²/h, with dose-limiting toxicities including severe neutropenia and herpes zoster observed at higher doses.

MK-0457 was generally well tolerated, with nearly half of the 27 patients experiencing stable disease, suggesting potential efficacy, particularly in combination with other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Traynor, AM., Hewitt, M., Liu, G., et al.[2022]

In a first-in-human trial involving 61 patients with advanced solid tumors, the maximum tolerated dose (MTD) of the Aurora A kinase inhibitor MLN8054 was determined to be 60 mg taken four times daily for 14 days, with reversible somnolence identified as the dose-limiting toxicity.

The study found that MLN8054 was rapidly absorbed and had a dose-proportional exposure, but the side effects limited the ability to reach plasma concentrations needed for effective target modulation, indicating the need for further investigation with a second-generation inhibitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors. Dees, EC., Infante, JR., Cohen, RB., et al.[2021]

In a phase II trial involving 16 patients with advanced solid tumors, vorinostat was found to be tolerable only at a dose of 200 mg twice daily, as higher doses led to significant dose-limiting toxicities such as anorexia and thrombocytopenia.

Despite some disease stabilization in eight patients, there were no confirmed responses to vorinostat, indicating that while it may be safe at lower doses, its efficacy in this patient population remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. Vansteenkiste, J., Van Cutsem, E., Dumez, H., et al.[2021]

K18, a new antitumor agent, demonstrated low acute toxicity in animal studies, indicated by high LD50 values, suggesting it is safe for further testing.

K18 effectively inhibited tumor growth in both an experimental animal model (Walker 256) and a human tumor model (RCC-13) in nude mice, and it showed a unique ability to accumulate and persist at the tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects of 3-[p-(N,N-bis-(2'-chloroethyl)amino)-phenyl]-L- alanine conjugated with human immunoglobulin (K18). Yoshimura, M., Niimura, K., Fujii, M., et al.[2013]

K18, a new antitumor agent combining human immunoglobulin with melphalan, showed promising antitumor effects in two animal models of metastasis, specifically in mice with Lewis lung carcinoma and colon-26 tumors.

Oral administration of K18 significantly reduced the number of lung nodules in mice with tumors transplanted via the tail vein, indicating its potential efficacy in treating metastatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effect of K18 on metastatic models. Fujii, T., Furusho, T., Niimura, K., et al.[2013]

In a study of 250 clear cell renal cell carcinoma (ccRCC) cases, higher levels of the transcription factor SOX18 were linked to more advanced cancer stages and poorer patient survival, suggesting its role in promoting cancer progression.

SOX18 not only enhances ccRCC carcinogenesis and metastasis but also helps cancer cells resist the effects of the drug cabozantinib, indicating that targeting SOX18 could be a potential strategy for improving ccRCC treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcription Factor SOX18 Promotes Clear Cell Renal Cell Carcinoma Progression and Alleviates Cabozantinib-Mediated Inhibitory Effects. Huaqi, Y., Caipeng, Q., Qiang, W., et al.[2020]

SOX18 and IL-6 levels are elevated in osteosarcoma compared to normal bone tissues, indicating their potential roles in the disease's progression.

IL-6 appears to regulate SOX18 expression, promoting osteosarcoma cell proliferation and inhibiting apoptosis, suggesting that targeting this pathway could be a therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-6 upregulates SOX18 expression in osteosarcoma. Wu, Z., Yang, W., Liu, J., et al.[2022]

SOX18 is overexpressed in osteosarcoma (OS) patients and cell lines, and its silencing leads to significant cell cycle arrest and apoptosis, as well as reduced migration and invasion of OS cells, indicating its role in promoting tumor malignancy.

The study suggests that targeting SOX18 could be a promising therapeutic strategy for osteosarcoma, as it regulates key proteins involved in cell growth and survival, such as p53 and Bcl-2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneous expression and biological function of SOX18 in osteosaroma. Zhu, D., Yang, D., Li, X., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

An appraisal of FDA approvals for adult solid tumours in 2017-2021: has the eagle landed? [2022]

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

Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. [2022]

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

Oncotype DX recurrence score implications for disparities in chemotherapy and breast cancer mortality in Georgia. [2023]

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

Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial. [2021]

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

Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. [2021]

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

Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors. [2021]

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

Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. [2021]

11. Greece pubmed.ncbi.nlm.nih.gov

Antitumor effects of 3-[p-(N,N-bis-(2'-chloroethyl)amino)-phenyl]-L- alanine conjugated with human immunoglobulin (K18). [2013]

12. Greece pubmed.ncbi.nlm.nih.gov

Antitumor effect of K18 on metastatic models. [2013]

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

Transcription Factor SOX18 Promotes Clear Cell Renal Cell Carcinoma Progression and Alleviates Cabozantinib-Mediated Inhibitory Effects. [2020]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Interleukin-6 upregulates SOX18 expression in osteosarcoma. [2022]

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

Heterogeneous expression and biological function of SOX18 in osteosaroma. [2018]