A Study to Evaluate a Single-Dose Subcutaneous Axatilimab Compared With Intravenous Axatilimab in Healthy Participants

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

72 Participants Needed

Trial Summary

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.

How does the drug Axatilimab differ from other treatments for this condition?

Axatilimab is unique because it targets the AXL receptor tyrosine kinase, which is involved in cancer progression and immune suppression. This mechanism can enhance the immune system's ability to fight cancer, especially when combined with immune checkpoint inhibitors, potentially offering benefits for patients who do not respond to standard immunotherapies. ^{1 2 3 4 5}

What is the purpose of this trial?

This study will be conducted to evaluate a Single-Dose Subcutaneous (SC) Axatilimab Compared With Intravenous Axatilimab in Healthy Participants.

Research Team

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Eligibility Criteria

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.

I can understand and am willing to sign the consent form for the study.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. Australia 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2022]

4. Germany 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. [2021]

5. United States 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. [2019]