Axatilimab for Healthy Subjects

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Incyte Corporation

Must not be taking: Antibiotics, Antifungals, Antivirals, others

Disqualifiers: Cardiovascular disease, Hypertension, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two methods of administering the experimental drug Axatilimab: injection under the skin and intravenous delivery. Researchers aim to determine how these methods affect the drug's performance in healthy individuals. It suits those who are generally healthy and can receive injections or IVs. 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 treatment.

Do I need to stop taking my current medications to join the trial?

Yes, you will need to stop taking prescription drugs within 14 days and nonprescription medications within 7 days before the study drug is given, except for occasional standard-dose acetaminophen, ibuprofen, and standard-dose vitamins.

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

Research has shown that axatilimab, administered either by IV (intravenous) infusion or SC (subcutaneous) injection, presents some safety concerns. For the IV form, about 18% of patients experienced infusion-related reactions, such as hypersensitivity, which might include symptoms like fever, chills, or rash.

For the SC injection, serious side effects occurred in 44% of patients, leading to pauses or adjustments in treatment. Both forms carry risks, but these reactions are known and monitored during treatment.

The FDA has approved axatilimab for treating a condition called cGVHD, indicating it has passed some safety checks for that use. However, different conditions and doses can affect treatment tolerance. It is important to discuss potential side effects with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Axatilimab is unique because it offers a new delivery method for treatment—subcutaneous (SC) injection, as opposed to the typical intravenous (IV) infusion. This could make administration easier and more comfortable for patients. Researchers are excited about these treatments because the SC injection might allow for more convenient dosing and potentially improve patient compliance. Additionally, axatilimab targets specific pathways within the immune system, which could offer more precise treatment options compared to existing therapies.

What evidence suggests that Axatilimab could be effective?

Research has shown that axatilimab holds promise for treating chronic graft-versus-host disease (cGVHD). Studies have found that 65% of patients with difficult-to-treat cGVHD responded well to this treatment. Additionally, 60% of patients did not require new treatments and remained alive after receiving axatilimab. In this trial, participants will receive axatilimab either as an intravenous (IV) infusion or as an under-the-skin (SC) injection across various cohorts. Both forms have effectively managed symptoms, with patients experiencing significant improvements, including fewer symptoms as measured by the Lee Symptom Scale. These findings suggest axatilimab could be a helpful treatment option for those dealing with cGVHD. ^{5 6 7 8 9}

Who Is on the Research Team?

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-55 with a BMI of 18.0 to 32.0 kg/m2, without significant health issues based on clinical evaluations. Participants must avoid pregnancy or fathering children and agree to contraception guidelines. Enrollment limits those with higher BMI and requires varied body weights across participants.

Inclusion Criteria

I am willing to prevent pregnancy or fathering children during the study.

My recent health screenings show no significant issues.

My BMI is between 18.0 and 32.0.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Axatilimab either subcutaneously or intravenously

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pharmacokinetics and safety, including adverse events and anti-drug antibody presence

3 months

Multiple visits on Days 2, 3, 4, 6, 8, 15, 22, 28, and 60

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab

Trial Overview The study tests a single dose of Axatilimab given subcutaneously (under the skin) versus intravenously (into a vein) in healthy individuals to compare the effects and outcomes between these two methods of administration.

How Is the Trial Designed?

Group I: Cohort D Experimental Treatment 1 Intervention

Axatilimab will be administered at a protocol defined starting dose administered as an SC injection.

Group II: Cohort C Experimental Treatment 1 Intervention

Axatilimab will be administered at a protocol defined starting dose administered as an SC injection.

Group III: Cohort B Experimental Treatment 1 Intervention

Axatilimab will be administered at a protocol defined starting dose administered as an SC injection.

Group IV: Cohort A Experimental Treatment 1 Intervention

Axatilimab will be administered at a protocol defined starting dose administered as an IV infusion.

Who Is Running the Clinical Trial?

Incyte Corporation

Lead 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

Axitinib, a multi-receptor tyrosine kinase inhibitor, not only inhibits tumor growth through VEGF-VEGFR pathways but also enhances anti-cancer immunity by reducing immune-suppressive cells like mast cells and tumor-associated macrophages, as shown in various murine tumor models.

Combining axitinib with immune checkpoint inhibitors (like anti-PD-1) and activating receptors (like CD137) resulted in a synergistic effect, improving T cell responses and therapeutic efficacy, highlighting its potential for enhancing cancer immunotherapy strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The multi-receptor inhibitor axitinib reverses tumor-induced immunosuppression and potentiates treatment with immune-modulatory antibodies in preclinical murine models. Läubli, H., Müller, P., D'Amico, L., et al.[2021]

Enapotamab vedotin (EnaV), an antibody-drug conjugate targeting the AXL receptor, effectively treats melanoma and lung cancer tumors that are resistant to immunotherapy, promoting tumor cell death and an inflammatory immune response.

Combining EnaV with tumor-specific T cells enhances the effectiveness of treatment, leading to improved responses to immune checkpoint blockade (ICB) in tumors that typically do not respond to anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cooperative Targeting of Immunotherapy-Resistant Melanoma and Lung Cancer by an AXL-Targeting Antibody-Drug Conjugate and Immune Checkpoint Blockade. Boshuizen, J., Pencheva, N., Krijgsman, O., et al.[2022]

SKI-G-801, a small-molecule inhibitor of AXL, effectively inhibited tumor growth and metastasis in various cancer models, demonstrating its potential as a standalone treatment and in combination with anti-PD-1 therapy.

The combination of SKI-G-801 and anti-PD-1 therapy significantly enhanced anti-tumor immune responses, leading to improved survival rates in mouse models, suggesting it could help overcome resistance to anti-PD-1 therapy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKI-G-801, an AXL kinase inhibitor, blocks metastasis through inducing anti-tumor immune responses and potentiates anti-PD-1 therapy in mouse cancer models. Synn, CB., Kim, SE., Lee, HK., et al.[2022]

Axitinib is an oral medication that inhibits key receptors involved in tumor growth and has shown activity against various solid tumors, including thyroid, pancreatic, lung, and breast cancers, based on Phase II trials.

While common side effects include fatigue and hypertension, axitinib was generally well tolerated, and larger randomized studies were underway to further evaluate its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Choueiri, TK.[2018]

Axl receptor tyrosine kinase plays a crucial role in cancer progression and immune suppression, and its inhibition enhances the immune response against tumors by increasing the activity of CD4+ and CD8+ T cells.

Combining Axl inhibition with PD-1 blockade shows strong synergistic effects in treating tumors, suggesting that targeting Axl could improve the effectiveness of immune checkpoint blockers in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axl inhibition induces the antitumor immune response which can be further potentiated by PD-1 blockade in the mouse cancer models. Guo, Z., Li, Y., Zhang, D., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11713947/

Axatilimab - PMC In patients who achieved a response, no death or new systemic therapy initiation was required in 60% (95% CI: 43%-74%) of patients in the 0.3 mg ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04710576

NCT04710576 | A Study of Axatilimab at 3 Different Doses ... This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842825002434

Efficacy and safety of axatilimab in chronic graft-versus- ... Axatilimab demonstrates robust clinical activity in refractory cGVHD. · Overall response rate reached 65 % in clinical trials. · 64 % of patients showed ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/761411Orig1s000MultidisciplineR.pdf

blamultidisciplinary review and evaluation - accessdata.fda.gov Axatilimab is administered as an IV infusion by healthcare professionals under the supervision of the investigator. Participants generally ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/31/17/3607/764195/FDA-Approval-Summary-Axatilimab-for-Adult-and

Axatilimab for Adult and Pediatric Patients Weighing at Least ... The median duration of response was 1.9 months (95% CI, 1.6–3.5), but 60% (95% CI, 43–74) of responding patients remained alive without new systemic therapy for ...

6. niktimvohcp.com niktimvohcp.com/safety-profile

Niktimvo ™ (axatilimab-csfr) safety profile Niktimvo ™ (axatilimab-csfr) can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761411s000lbl.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION These ... NIKTIMVO (axatilimab-csfr) injection is a sterile, preservative-free, slightly opalescent, pale brownish yellow solution for intravenous use. The solution is ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1/499054/Safety-and-Efficacy-of-Axatilimab-at-3-Different

Safety and Efficacy of Axatilimab at 3 Different Doses in ... Patients were heavily pretreated with a median of 4 prior lines of therapy, including ruxolitinib (74%), belumosudil (23%), and ibrutinib (31%).

9. aetna.com aetna.com/cpb/medical/data/1000_1099/1069.html

Axatilimab-csfr (Niktimvo) - Medical Clinical Policy Bulletins In August 2024, the FDA approved axatilimab-csfr (Niktimvo) for the treatment of cGVHD after failure of at least two prior lines of systemic therapy in adult ...