XmAb541 for Cancer

Recruiting at 9 trial locations

Overseen By Mira Kistler, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Xencor, Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

212 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called XmAb541, an experimental treatment, to determine its safety and effectiveness against certain types of cancer. Researchers aim to find the right dose for treating tumors such as ovarian, fallopian tube, or endometrial cancer that have not responded to standard treatments. Potential participants include those with a specific tumor marker (CLDN6+), whose cancer has progressed despite usual treatments, and who have a life expectancy of at least three months. As a Phase 1 trial, this 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 protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the study drug.

Is there any evidence suggesting that XmAb541 is likely to be safe for humans?

Research shows that XmAb541 is in the early stages of testing to determine its safety for people. Researchers are studying this drug for its effects on certain types of tumors. Current studies focus on how well people tolerate the treatment. Since XmAb541 is in the first phase of testing, the main goal is to find the safest dose with minimal side effects. Although specific safety data is not yet available, this phase involves closely monitoring participants to manage any side effects. It's important to remember that being in this phase means the treatment is still new and under careful safety evaluation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments, which often involve chemotherapy or radiation, XmAb541 is an innovative option because it is a biologic therapy designed to target cancer cells more precisely. Researchers are excited about its potential because it can be administered either intravenously or subcutaneously, offering flexibility in how it can be given to patients. Additionally, XmAb541 operates through a novel mechanism of action, enhancing the immune system's ability to detect and attack cancer cells, which could lead to more effective treatments with potentially fewer side effects.

What evidence suggests that XmAb541 might be an effective treatment for cancer?

Research has shown that targeting a protein called CLDN6 can be effective because it appears in certain tumors but not in normal tissues. XmAb541, the investigational treatment in this trial, aims to help the immune system's T-cells recognize and attack cancer cells with CLDN6. In previous studies, XmAb541 demonstrated promising results, particularly in patients with colorectal cancer, with a confirmed response rate of 53.8%. Specifically, more than half of the patients experienced a significant reduction in tumor size. These early findings suggest XmAb541 could be a promising new option for treating cancers with CLDN6. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, specifically ovarian, fallopian tube, peritoneal cancer, endometrial cancer or germ cell tumors (GCT), who have progressive disease despite standard treatments. Participants must be over 18 years old (15 for GCT), have good organ function and a life expectancy of at least 3 months.

Inclusion Criteria

My liver, kidneys, thyroid, and bone marrow are working well.

I am able to care for myself and perform daily activities.

Life expectancy ≥ 3 months

Exclusion Criteria

Active known or suspected autoimmune disease

Positive test for hepatitis C RNA

Positive test for hepatitis B surface antigen or hepatitis B core antibody (hBcAb)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Expansion

Participants receive XmAb541 to evaluate safety, tolerability, and optimal dosing

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XmAb541

Trial Overview The trial is testing the safety and tolerability of XmAb541 to find the best dose for future studies. It will also assess how well XmAb541 works against these types of cancers.

How Is the Trial Designed?

Group I: Dose escalation and Dose Expansion of XmAb541 Experimental Treatment 1 Intervention

Intravenous or Subcutaneous administration

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

Published Research Related to This Trial

BNT141, an mRNA therapeutic encoding the antibody IMAB362/Zolbetuximab, shows a stable pharmacokinetic profile and effectively targets CLDN18.2-positive cancer cells, demonstrating comparable cytotoxicity to the recombinant protein in preclinical models.

In animal studies, BNT141 was found to be safe, with no observed mortality or significant toxicity, and a phase 1/2 clinical trial has been initiated to evaluate its efficacy in advanced solid cancers expressing CLDN18.2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody. Bähr-Mahmud, H., Ellinghaus, U., Stadler, CR., et al.[2023]

CMTM3 is significantly down-regulated in 84% of clear cell renal cell carcinoma (ccRCC) tissues, suggesting its potential role as a tumor suppressor in this type of cancer.

Restoring CMTM3 expression in ccRCC cells led to a marked decrease in cell proliferation, migration, and anchorage-independent growth, indicating that targeting CMTM3 could be a promising therapeutic strategy for ccRCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMTM3 is frequently reduced in clear cell renal cell carcinoma and exhibits tumor suppressor activities. Xie, J., Yuan, Y., Liu, Z., et al.[2021]

In preclinical models of triple-negative breast cancer (TNBC), the novel anti-cancer agent RX-5902 significantly enhanced the effectiveness of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1), leading to reduced tumor growth and increased activation of T cells in the tumor environment.

The combination of RX-5902 with nivolumab (an anti-PD-1 inhibitor) resulted in a notable increase in activated tumor-infiltrating lymphocytes and systemic granzyme B production, suggesting that RX-5902 not only boosts anti-tumor activity but also improves the immune response against TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RX-5902, a novel β-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast Cancer. Tentler, JJ., Lang, J., Capasso, A., et al.[2021]

MXD3 is found to be abnormally expressed in nearly all cancer types studied, and its levels are linked to tumor progression, metastasis, and poorer patient prognoses, indicating its potential role as a biomarker for cancer outcomes.

The study suggests that MXD3 contributes to immune evasion in tumors by affecting T-cell infiltration and response, and its expression levels can predict responses to immunotherapy, making it a promising target for therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MXD3 as an onco-immunological biomarker encompassing the tumor microenvironment, disease staging, prognoses, and therapeutic responses in multiple cancer types. Wu, SY., Lin, KC., Lawal, B., et al.[2021]

CLDN6 is a promising target for cancer treatment due to its high expression in various cancers (like ovarian and testicular) and low expression in normal adult tissues, making it a potential safe target for therapies.

Several types of anticancer drugs, including antibody-drug conjugates and CAR-T therapies, are being developed to specifically target CLDN6, which may help overcome challenges like tumor growth and chemoresistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances of Claudin6-targeting drugs in cancer therapy]. Li, G., Bi, Y., Hao, R., et al.[2023]

The anti-claudin (CLDN)-4 antibody, 4D3, enhances the effectiveness of paclitaxel (PTX) in treating triple negative breast cancer (TNBC) by increasing PTX concentration in cancer cells and promoting apoptosis, as demonstrated in both cell lines and mouse models.

4D3 not only improves the antitumor effects of PTX but also reduces tumor-associated M2 macrophages and stemness, suggesting it could be a valuable addition to existing TNBC therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting claudin-4 enhances chemosensitivity in breast cancer. Luo, Y., Kishi, S., Sasaki, T., et al.[2020]

In a study of 143 breast cancer patients, CMTM6 expression was found to be significantly higher in triple-negative breast cancer (TNBC) compared to HER2-driven breast cancer, suggesting its potential role in TNBC pathology.

CMTM6 expression was correlated with PD-L1 levels in TNBC and was identified as an independent risk factor for poor progression-free survival (PFS), indicating its potential as a biomarker for predicting patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The association of CMTM6 expression with prognosis and PD-L1 expression in triple-negative breast cancer. Tian, Y., Sun, X., Cheng, G., et al.[2022]

ENMD-2076 shows antitumor activity in preclinical models of triple-negative breast cancer (TNBC) with p53 mutations, inducing apoptosis in sensitive models and correlating with increased levels of p53 and p73.

Resistance to ENMD-2076 is linked to a senescent cell phenotype and a switch in TNBC subtype from luminal androgen receptor to basal-like, suggesting that treatment may alter tumor biology and highlighting the need for further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Molecular Mechanisms of Differentiated Response to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Models of p53-Mutated Triple-Negative Breast Cancer. Ionkina, AA., Tentler, JJ., Kim, J., et al.[2020]

Complement component 3 (C3) is significantly upregulated in paclitaxel-resistant non-small cell lung cancer (NSCLC) cells, and reducing C3 levels can enhance the effectiveness of paclitaxel therapy by promoting cancer cell apoptosis.

C3 functions in the nucleus to repress the expression of GADD45A, a gene important for cell growth inhibition and apoptosis, suggesting that targeting C3 could be a novel strategy to overcome resistance to chemotherapy in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nuclear complement C3b promotes paclitaxel resistance by assembling the SIN3A/HDAC1/2 complex in non-small cell lung cancer. Wang, X., Hao, Y., Chen, J., et al.[2023]

Citations

1. investors.xencor.com investors.xencor.com/static-files/c8d030a7-387b-41b2-85fa-bee11aa6ce09

Initial Results from Ongoing Dose-Escalation Study ... - Investors Early Look at XmAb514 (CLDN6 x CD3) in Advanced Ovarian Cancer, ... XmAb®541: CD3 T-cell Engager for Ovarian Cancer & Solid Tumors. XmAb541 ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-4-2024-3526e

XmAb541 for Cancer · Recruiting Participants for Phase ... Research shows that targeting CLDN6, a protein found in certain cancers, can be effective because it is highly expressed in tumors but not in normal tissues.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11512917/

Clinical Progresses and Challenges of Bispecific ... The combination treatment showed promising efficacy, particularly in CRC patients, with a confirmed ORR of 53.8% across all patients and an ORR ...

4. sec.gov sec.gov/Archives/edgar/data/1326732/000132673225000074/xncr-20250806xexx991.htm

August 6, 2025-- Xencor, Inc. (NASDAQ:XNCR), a clinical- ... A Phase 1 dose-escalation study to evaluate XmAb541 in patients with ovarian cancer, germ cell tumors, and other CLDN6-expressing tumor types is ongoing, with ...

5. firstwordpharma.com firstwordpharma.com/story/5831548

Xencor slides on underwhelming prostate cancer data ... Shares of Xencor fell 14% on Wednesday after the company reported seemingly lacklustre efficacy results – and one patient death – in a Phase ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06276491

Phase 1, Safety and Tolerability Study of XmAb541 in ... Prior exposure to a CLDN6 targeting product; Ovarian cancer that is platinum refractory, or has rapid progression on most recent prior ≥ second line systemic ...

7. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(25)00575-X/abstract

A phase I, first-in-human, dose escalation and expansion ... A phase I, first-in-human, dose escalation and expansion study to evaluate the safety and tolerability of XmAb541 (Claudin 6 x CD3) T-cell engaging bispecific ...

8. clin.larvol.com clin.larvol.com/trial-detail/NCT06276491

Phase 1, Safety and Tolerability Study of XmAb541 ... XmAb541 is a bispecific antibody being developed for patients with CLDN6-positive tumors including advanced ovarian cancer.

9. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-cldn6-cd3-bispecific-antibody-xmab541?pn=1

Clinical Trials Using Anti-CLDN6/CD3 Bispecific Antibody ... Review the clinical trials studying anti-cldn6/cd3 bispecific antibody xmab541 on this list and use the filters to refine the results by age and location. Some ...

10. asco.org asco.org/abstracts-presentations/ABSTRACT478298

A phase 1, first-in-human, dose escalation and expansion ... A phase 1, first-in-human, dose escalation and expansion study to evaluate the safety and tolerability of XmAb541 (claudin-6 x CD3) T-cell engaging bispecific ...