XmAb27564 for Safety Evaluation

Overseen By Ralph Zitnik, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Xencor, Inc.

Disqualifiers: Cardiovascular event, Viral infection, Asthma, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new drug, XmAb27564, administered as a single injection under the skin. The researchers aim to understand how the body processes this drug in healthy individuals by using different doses to observe its behavior. Participants will receive either the actual drug or a placebo, which is a harmless, inactive substance used for comparison. The trial seeks healthy individuals who do not smoke, have no significant medical issues, and weigh between 50 to 100 kg. Those who meet these criteria and agree to follow birth control guidelines during the study might be a good match for this trial. 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. However, since the study is for healthy subjects with no significant health issues, it's possible that taking certain medications might exclude you from participating. It's best to discuss your specific medications with the trial coordinators.

Is there any evidence suggesting that XmAb27564 is likely to be safe for humans?

Research has shown that XmAb27564 was well-tolerated in past studies. A single dose of this treatment did not cause any serious health problems. Specifically, participants who received one dose experienced no major health issues linked to it. While treatments like high-dose IL2 have caused serious side effects, XmAb27564 has demonstrated a safer profile so far. This suggests it might be a promising option for future therapies, though the research is still in its early stages. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments that are often administered orally or intravenously, XmAb27564 is unique because it is delivered via a simple subcutaneous injection. This new approach targets specific immune pathways, potentially offering a more precise mechanism of action compared to existing therapies. Researchers are excited about XmAb27564 because it could offer improved tolerability and flexibility in dosing, making it a promising option for patients seeking more convenient and potentially more effective treatment alternatives.

What evidence suggests that XmAb27564 might be an effective treatment?

Research shows that XmAb27564, which participants in this trial may receive, is designed to interact with a protein in the immune system called interleukin-2. It aims to increase the number of regulatory T cells, which help manage the immune system and might benefit conditions like psoriasis. Earlier studies with similar treatments, such as XmAb564, found that it was well-tolerated and significantly increased these regulatory T cells. This suggests that XmAb27564 could effectively adjust immune responses for certain conditions. However, more research is needed to confirm its effectiveness for specific diseases. ^{2 4 6 7 8}

Who Is on the Research Team?

Ralph Zitnik, MD

Principal Investigator

Executive Medical Director, Clinical Development, Xencor

Are You a Good Fit for This Trial?

Inclusion Criteria

A nonsmoker for at least 12 weeks preceding screening

Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 45 days after administration of investigational product (IP).

Fertile male and female subjects must be willing to practice a highly effective method of birth control during and for 45 days after administration of IP and agree not to donate sperm from screening through 45 days after administration of IP.

Exclusion Criteria

Subjects with vital sign values outside the normal ranges

Subjects who are positive for MTB QuantiFERON, hepatitis B surface antigen, hepatitis C virus antibody, severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) by polymerase chain reaction (PCR)/antigen, or human immunodeficiency virus Type I or Type II tests at screening

Subjects who have evidence of any bacterial, viral, parasitic, or systemic fungal infections requiring treatment within the 21 days prior to randomization; or hospitalization due to infection within 3 months prior to randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subcutaneous injection of XmAb27564 or placebo in a randomized, double-blind, placebo-controlled manner

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and pharmacokinetics after receiving the injection

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• XmAb27564

How Is the Trial Designed?

Group I: Single Ascending Dose - XmAb27564 Subcutaneous injection of Dose A, B, C, D, E or F Experimental Treatment 1 Intervention

Group II: Single Ascending Dose - Placebo Subcutaneous injection of placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

ICON Clinical Research

Industry Sponsor

Trials

52

Recruited

15,100+

Published Research Related to This Trial

In a study involving 97 patients with malignant gliomas, temozolomide (TMZ) demonstrated a significantly higher response rate (35.71%) compared to lomustine (CCNU) (9.09%), indicating its greater efficacy in treating these aggressive brain tumors.

TMZ was found to have an acceptable safety profile, with common side effects being mild nausea and vomiting, suggesting it could be a preferred chemotherapy option for patients with refractory malignant brain gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. Qian, ZZ., Wang, HQ., Liu, XM., et al.[2018]

Temozolomide (TMZ) and the checkpoint kinase inhibitor AZD7762 both showed time- and concentration-dependent cytotoxic effects on human glioma cells, with their combination resulting in synergistic effects that enhance cell death.

The combination treatment of TMZ and AZD7762 not only suppressed the expression of the DNA repair protein MGMT but also modulated several signaling pathways, suggesting a complex mechanism that may improve the efficacy of glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and AZD7762 Induce Synergistic Cytotoxicity Effects on Human Glioma Cells. Chen, Y., Tseng, BJ., Tsai, YH., et al.[2022]

In a phase I trial involving 38 patients with advanced solid tumors, the combination of intravenous methoxyamine (MX) and oral temozolomide (TMZ) was found to be safe, with no dose-limiting toxicities observed, allowing for a maximum tolerated dose of TMZ at 200 mg/m² daily for 5 days alongside MX at 150 mg/m² on day 1.

The trial showed that while there were some grade 3 and 4 adverse events, the combination therapy resulted in a partial response in one patient and prolonged stable disease in six others, suggesting potential efficacy in certain tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors. Eads, JR., Krishnamurthi, SS., Saltzman, J., et al.[2022]

Citations

1. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-presents-clinical-results-phase-1a-study-xmabr564-eular

Xencor Presents Clinical Results from Phase 1a Study of ... A single dose of XmAb564 was well tolerated in healthy volunteers and generates durable, dose-dependent and selective expansion of regulatory T cells.

2. withpower.com withpower.com/trial/phase-1-dermatitis-dermatitis-atopic-9-2022-5db32

XmAb27564 for Psoriasis · Info for Participants In a phase IIIb study involving 119 patients with moderate-to-severe plaque psoriasis, guselkumab was significantly more effective than fumaric acid esters (FAE) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06005792

NCT06005792 | Multiple Ascending-Dose Study of XmAb® ... The purpose of this study is to evaluate the safety and tolerability of XmAb27564 following multiple doses among participants with plaque psoriasis and atopic ...

4. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencors-il2-fc-cytokine-xmabr564-well-tolerated-and-selectively

Xencor's IL2-Fc Cytokine, XmAb®564, is Well-tolerated and ... XmAb564 is a wholly owned, monovalent interleukin-2 Fc fusion protein (IL-2-Fc), engineered with dramatically lowered potency and heightened binding affinity ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10111960/

A systematic review of interleukin-2-based ... ... XmAb27564 lists one registered clinical trial currently recruiting healthy participants. ... All reported data have been verified by at least two authors, MR and ...

6. withpower.com withpower.com/trial/phase-1-3-2021-b2bf6

Safety, Tolerability and PK of a Single Subcutaneous ... TMZ was found to have an acceptable safety profile, with common side effects being mild nausea and vomiting, suggesting it could be a preferred chemotherapy ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11977552/

Cytokine Couture: Designer IL2 Molecules for the ... In addition, off target effects of high dose IL2 can lead to serious side effects, such as vascular leak syndrome (VLS). Many of the early disappointments ...

8. biospace.com biospace.com/xencor-s-il2-fc-cytokine-xmab-564-is-well-tolerated-and-selectively-expands-regulatory-t-cells-in-phase-1a-clinical-study

Xencor's IL2-Fc Cytokine, XmAb®564, is Well-tolerated ... -- Single dose of XmAb564 well-tolerated with no reported serious adverse events --. -- First patient dosed in Phase 1b, multiple-ascending ...