Ruxolitinib for Non-Small Cell Lung Cancer Cachexia

Overseen By Jonathan VanPelt

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Tu Dan

Must not be taking: CYP3A4 inhibitors, Fluconazole

Disqualifiers: Stage I-III NSCLC, Actionable mutations, Active malignancy, Uncontrolled illness, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of Ruxolitinib, a medication for individuals with non-small cell lung cancer (NSCLC) experiencing cachexia, a syndrome causing severe weight loss and muscle wasting. Researchers aim to determine if this treatment can help by examining specific signals in the body before and after drug administration. It targets those diagnosed with advanced NSCLC who have recently lost more than 5% of their body weight. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to groundbreaking medical knowledge.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are taking strong CYP3A4 inhibitors and fluconazole, as these are excluded.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking therapies that are strong CYP3A4 inhibitors and fluconazole. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that ruxolitinib is generally well-tolerated, meaning most people can use it without serious problems. In previous studies, experts found no unexpected safety issues with this drug. Ruxolitinib is already approved for treating some blood disorders and an immune disease, indicating its safety is well-known. However, like any medication, it can have side effects. When used for immune system conditions, some patients experienced a higher risk of infections and other immune-related problems. These findings suggest it is safe, but this trial specifically aims to assess the safety of ruxolitinib for people with non-small cell lung cancer cachexia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for non-small cell lung cancer cachexia, which mainly focus on nutritional support and anti-inflammatory drugs, Ruxolitinib acts on a different level by targeting specific pathways involved in inflammation and muscle wasting. Researchers are excited about Ruxolitinib because it inhibits the JAK1 and JAK2 enzymes, which are key players in these pathways. This targeted approach has the potential to directly address the underlying causes of cachexia, offering hope for more effective management of this challenging condition.

What evidence suggests that Ruxolitinib might be an effective treatment for NSCLC cachexia?

Research has shown that ruxolitinib might help with cancer cachexia, a condition causing severe weight and muscle loss. One study found that ruxolitinib improved the health and nutrition of patients with a type of blood cancer, suggesting potential benefits for overall health. Animal studies have found that this treatment can increase survival and improve body weight without affecting tumor growth. This indicates that ruxolitinib might help manage weight loss in cancer patients by targeting a specific pathway involved in inflammation and muscle wasting. These findings are promising, but more research is needed to confirm its effectiveness for weight loss in patients with non-small cell lung cancer. Participants in this trial will receive different dosing regimens of ruxolitinib to evaluate its impact on cachexia in non-small cell lung cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Tu Dan

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

Adults with advanced Non-Small Cell Lung Cancer and cachexia can join this trial. They must have a life expectancy of at least 6 months, no prior treatment for their lung cancer, and agree to use contraception. Those with certain mutations or other active cancers, previous JAK inhibitor treatments, or serious health issues like heart failure are excluded.

Inclusion Criteria

You have been diagnosed with non-small cell lung cancer, confirmed by a biopsy or tissue sample.

Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation

You are expected to live for at least 6 more months.

Exclusion Criteria

You are currently taking part in another clinical trial for treating lung or other cancers.

Females who are pregnant, breast-feeding or plan to become pregnant

Any other conditions that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ruxolitinib with dose escalation over 3 months to assess toxicity and impact on cancer cachexia

3 months

Bi-weekly visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life and body weight assessments

1 month

Bi-weekly visits

Long-term Follow-up

Progression-free survival and overall survival assessments at 6 months from start of active phase

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The trial is testing the safety of Ruxolitinib in treating cachexia in lung cancer patients. It aims to find any toxic effects from different doses and see how it affects signaling pathways related to muscle and fat tissue before and after treatment.

How Is the Trial Designed?

Group I: Dosing Regimen for Ruxolitinib Experimental Treatment 1 Intervention

Level 0: Ruxolitinib 0 MG po bid for 1 month (Month 1) Level 1: Ruxolitinib 10 MG po bid for 1 month (Month 2) Level 2: Ruxolitinib 15 MG po bid for 1 month (Month 3)

Ruxolitinib is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Tu Dan

Lead Sponsor

Trials

1

Recruited

10+

Puneeth Iyengar

Lead Sponsor

Trials

1

Recruited

10+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

Ruxolitinib, a JAK1/2 inhibitor, was evaluated in a Phase Ib study with 42 patients, primarily with pancreatic cancer, showing it was generally safe and well tolerated when combined with gemcitabine, although the study was terminated early due to interim results from another study.

The overall response rate for the combination therapy was 38.5% in the pooled cohorts, but the study was halted before determining maximum tolerated doses, indicating that while there was some efficacy, the combination will not be pursued further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors. Bauer, TM., Patel, MR., Forero-Torres, A., et al.[2022]

In a pilot study involving two patients with myelofibrosis treated with ruxolitinib, both experienced an increase in waist circumference, indicating weight gain as a side effect of the medication.

The study suggested that the weight gain associated with ruxolitinib may be linked to changes in energy expenditure, as initial increases in energy expenditure were followed by decreases, ultimately remaining below baseline levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy expenditure in myelofibrosis patients treated with a JAK1/2 inhibitor. Tremblay, D., Dougherty, M., Mascarenhas, J., et al.[2023]

In a study of 127 patients with myeloproliferative neoplasms treated with ruxolitinib, significant weight gain was observed, with 50% of patients gaining more than 5% body weight over 72 weeks, indicating a notable metabolic effect of the drug.

Ruxolitinib treatment was associated with increased systolic blood pressure and elevated liver enzymes (AST and ALT), suggesting potential long-term metabolic consequences that need to be monitored in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms. Sapre, M., Tremblay, D., Wilck, E., et al.[2021]

In the COMFORT-I study, ruxolitinib significantly improved metabolic and nutritional status in patients with intermediate-2 or high-risk myelofibrosis, leading to increased weight, cholesterol, and albumin levels compared to placebo.

Ruxolitinib treatment not only reduced spleen size and improved symptoms but also showed sustained benefits in metabolic parameters over time, indicating its potential as a comprehensive treatment for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I. Mesa, RA., Verstovsek, S., Gupta, V., et al.[2021]

Erlotinib showed slightly better outcomes than gefitinib in treating non-small cell lung cancer (NSCLC), although the differences were not statistically significant, indicating that both drugs are viable options.

Molecular markers such as high levels of phosphorylated EGFR (pEGFR), pAKT, and pSTAT3 were associated with longer time to progression in patients, suggesting that tumors with these activated pathways may respond better to treatment with tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to gefitinib and erlotinib in Non-small cell lung cancer: a restrospective study. Emery, IF., Battelli, C., Auclair, PL., et al.[2021]

In three cases of advanced bronchioloalveolar carcinoma, treatment with 250 mg of Gefitinib (Iressa) once daily resulted in significant antitumor effects.

Gefitinib showed remarkable clinical responses in patients with poor performance status who had previously undergone extensive chemotherapy, suggesting its potential as an effective treatment option in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gefitinib for advanced bronchioloalveolar carcinoma]. Zhang, XT., Wang, SL., Li, LY.[2018]

Gefitinib has shown antitumor activity in lung cancer patients, with phase I trials indicating it is well tolerated at doses effective for treatment, leading to objective response rates of 10-20% in phase II trials with minimal toxicity.

While combining gefitinib with chemotherapy in phase III trials did not improve survival rates for patients with advanced non-small cell lung cancer, it did not significantly increase overall toxicity, suggesting potential for further studies with different treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefitinib (Iressa) trials in non-small cell lung cancer. Johnson, DH.[2019]

Ruxolitinib, an oral Janus kinase inhibitor, was found to be rapidly absorbed and well tolerated in a study involving 40 Japanese subjects, with no significant safety concerns reported.

The study showed that ruxolitinib's pharmacokinetics were similar in Japanese participants compared to non-Japanese populations, indicating consistent efficacy and safety across different ethnic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized dose-escalation study to assess the safety, tolerability, and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers. Ogama, Y., Mineyama, T., Yamamoto, A., et al.[2022]

In a study of 47 patients with T790M-positive advanced non-small cell lung cancer (NSCLC), body size variables like body surface area (BSA) and body mass index (BMI) did not significantly affect the efficacy of osimertinib, with similar response rates and progression-free survival across different body size groups.

The study found that osimertinib's effectiveness remained consistent regardless of body size, and factors such as better performance status, younger age, and specific genetic mutations (EGFR exon 19 deletion) were identified as more important predictors of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of osimertinib efficacy according to body surface area and body mass index in patients with non-small cell lung cancer harboring an EGFR mutation: A prospective observational study. Ono, T., Igawa, S., Ozawa, T., et al.[2022]

Ruxolitinib, a drug approved for myelofibrosis, shows potential as an anti-cancer agent when combined with ERBB1/2/4 inhibitors, effectively killing various solid tumor cells, including breast and lung cancers.

The combination therapy triggers significant cellular mechanisms, including mitophagy and the activation of apoptosis pathways, leading to reduced tumor growth in preclinical models, suggesting it warrants further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationally Repurposing Ruxolitinib (Jakafi (®)) as a Solid Tumor Therapeutic. Tavallai, M., Booth, L., Roberts, JL., et al.[2023]

In a study of 65 patients with advanced non-small cell lung cancer, those receiving molecular targeted therapies (EGFR and ALK TKIs) experienced significantly less skeletal muscle loss compared to those undergoing cytotoxic chemotherapy.

The analysis showed that the loss of muscle area was notably higher in the chemotherapy group, indicating that TKIs may be a safer option in terms of preserving muscle mass during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in skeletal muscle loss caused by cytotoxic chemotherapy and molecular targeted therapy in patients with advanced non-small cell lung cancer. Kakinuma, K., Tsuruoka, H., Morikawa, K., et al.[2018]

Ruxolitinib is shown to be safe and effective for treating myelofibrosis in Japanese patients, with 86.3% of the 51 participants completing the 24-week study and no deaths reported.

At 24 weeks, 30% of patients had significant reductions in spleen size, and there were notable improvements in symptoms and quality of life, even among those with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. Komatsu, N., Kirito, K., Shimoda, K., et al.[2021]

Ruxolitinib, a drug for treating intermediate or high-risk myelofibrosis, was studied in a population of 272 subjects, revealing that its pharmacokinetics can be accurately described by a two-compartment model, indicating effective absorption and elimination.

The study found that while gender and body weight influence the drug's clearance and distribution, these effects are not clinically significant, meaning no dose adjustments are necessary based on these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of orally-administered ruxolitinib (INCB018424 Phosphate) in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET MF). Chen, X., Williams, WV., Sandor, V., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04906746

NCT04906746 | Ruxolitinib for Cancer Cachexia To describe any preliminary evidence suggesting that Ruxolitinib suppresses body weight loss in cancer cachexia patients. Body weight will be measured every 2 ...

2. clinicaltrial.be clinicaltrial.be/en/details/43386?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Ruxolitinib for Cancer Cachexia To describe any preliminary evidence suggesting that Ruxolitinib suppresses body weight loss in cancer cachexia patients. Body weight will be ...

3. withpower.com withpower.com/trial/phase-1-cachexia-9-2021-e86a5

Ruxolitinib for Non-Small Cell Lung Cancer Cachexia In the COMFORT-I study, ruxolitinib significantly improved metabolic and nutritional status in patients with intermediate-2 or high-risk myelofibrosis, leading ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7580845/

JAK Inhibitors Suppress Cancer Cachexia-Associated ... Mice implanted with colon adenocarcinoma C26c20 cells and treated with ruxolitinib had an ~20–30% increase in median survival compared to mice receiving C26c20 ...

5. biorxiv.org biorxiv.org/content/10.1101/2025.10.21.683287v1.full-text

JAK1/2 Inhibition Delays Cachexia and Improves Survival ... Pharmacologic inhibition of JAK1/2 with ruxolitinib improved body weight, fat mass, and overall survival without altering tumor burden. These ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602646/

Clinical Review - Ruxolitinib (Jakavi) - NCBI - NIH According to the clinical experts consulted by CADTH, no unexpected safety concerns were observed with ruxolitinib. Go to: Introduction. Disease Background.

7. hcp.jakafi.com hcp.jakafi.com/acute-graft-versus-host-disease/safety-adverse-events

Safety Profile of Jakafi in aGVHD Learn about the safety profile of Jakafi® (ruxolitinib) in the treatment of patients with steroid-refractory acute graft-versus-host disease (aGVHD).

8. opzelura.com opzelura.com/opzelura-prescribing-information

Prescribing Information Cancer and immune system problems: OPZELURA may increase your risk of certain cancers by changing the way your immune system works. Lymphoma and other cancers ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/202192Orig1s000.pdf

202192Orig1s000 - accessdata.fda.gov This new drug application provides for the use of Jakafi™ (ruxolitinib) Tablets for the treatment of patients with intermediate or high-risk ...