XmAb®819 for Renal Cell Carcinoma

Recruiting at 9 trial locations

Overseen By Chet Bohac, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Xencor, Inc.

Must not be taking: Antineoplastics, Monoclonal antibodies

Disqualifiers: CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 2

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called XmAb819, a bispecific antibody, for individuals with clear cell renal cell carcinoma, a type of kidney cancer that has recurred or not responded to other treatments. The main goal is to assess the treatment's safety and determine the optimal dose. Suitable candidates for this trial have kidney cancer that is worsening despite standard treatments, which can be identified by observing tumor growth. 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.

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, you cannot have had systemic cancer treatment within a certain period before starting the trial, so you may need to discuss this with the trial team.

Is there any evidence suggesting that XmAb®819 is likely to be safe for humans?

Research has shown that XmAb819 is generally well-tolerated by patients with advanced clear cell renal cell carcinoma (ccRCC). In earlier studies, patients who had already tried many treatments experienced manageable side effects with XmAb819. Although the specific side effects weren't listed, the treatment achieved a 25% overall response rate, meaning one in four patients saw their tumors shrink. This indicates effectiveness for some patients without major safety issues. Overall, current evidence suggests that XmAb819 is relatively safe, especially given the complexity of advanced cancer cases. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for renal cell carcinoma, like targeted therapies or immunotherapies, work by disrupting cancer cell growth or enhancing the immune system’s ability to attack tumors. But XmAb819 works differently, targeting a specific protein on cancer cells to potentially improve the immune response against them. Researchers are excited because this approach could offer a more precise attack on cancer cells while possibly reducing side effects compared to the broader action of existing treatments. Additionally, XmAb819 is being tested in both intravenous and subcutaneous forms, offering flexible administration options that could improve patient comfort and convenience.

What evidence suggests that XmAb819 might be an effective treatment for renal cell carcinoma?

Research has shown that XmAb819 may benefit patients with advanced clear cell renal cell carcinoma (ccRCC) who have undergone extensive treatment. Early results indicate that about 25% of these patients responded well to the treatment. XmAb819 aids the body's immune cells, called T-cells, in locating and attacking cancer cells. The treatment is generally well-tolerated, with most patients not experiencing serious side effects. This trial will explore different dosing schedules of XmAb819, administered either intravenously or subcutaneously, to determine the most effective and safe approach. These findings suggest XmAb819 could be a useful option for people with difficult-to-treat kidney cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Chet Bohac, MD

Principal Investigator

Xencor, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced clear cell renal cell carcinoma who have seen their cancer return or not respond to standard treatments. They must be relatively healthy (ECOG status 0 or 1), have a tumor sample available, and measurable disease. People can't join if they've had certain recent cancers, brain metastases, serious allergies to monoclonal antibodies, autoimmune diseases, or significant infections recently.

Inclusion Criteria

My cancer can be measured by scans and has grown in previously treated areas.

I am fully active or can carry out light work.

My kidney cancer has returned and worsened despite treatment.

Exclusion Criteria

I have another cancer that is getting worse or was treated in the last 2 years.

I have an autoimmune disease but it's either vitiligo, type 1 diabetes, manageable thyroid issues, skin conditions not needing systemic treatment, or arthritis treated without strong medication.

I haven't taken cancer drugs within a period before starting the study treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Establish the dosing schedule for XmAb819 administered IV and SC, including priming and step-up doses

8 weeks

Weekly visits for dose adjustments and monitoring

Dose Expansion (Part B)

Administer XmAb819 IV or SC to further evaluate safety, tolerability, and preliminary antitumor activity

8 weeks

Bi-weekly visits for treatment and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• XmAb819

Trial Overview The study tests XmAb®819 given through IV or SC injections in patients with relapsed/refractory kidney cancer. It aims to find the safest and most effective dose that shows biological activity against the cancer.

How Is the Trial Designed?

Group I: Dose Escalation and Expansion Experimental Treatment 1 Intervention

Dose Escalation (Part A): Part A will establish the dosing schedule for XmAb819 administered IV and the dosing schedule of XmAb819 administered SC in subjects with ccRCC. The dosing schedule includes the priming dose, step-up priming dose(s), the minimum safe and biologically active dose. Dose Expansion (Part B): Part B-1 may administer XmAb819 IV, and Part B-2 may administer XmAb819 SC.

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

Published Research Related to This Trial

Pretargeting with a bispecific antibody and a (90)Y-peptide significantly increased the amount of radioactivity delivered to colorectal tumors, resulting in a 2.5-fold increase in tumor radioactivity compared to conventional (90)Y-IgG treatment.

This method not only improved therapeutic efficacy, leading to better survival rates and tumor ablation, but also reduced hematologic toxicity, making it a safer option at higher doses compared to traditional radioimmunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic advantage of pretargeted radioimmunotherapy using a recombinant bispecific antibody in a human colon cancer xenograft. Karacay, H., Brard, PY., Sharkey, RM., et al.[2006]

The study developed an effective pretargeting strategy for renal cell carcinoma (RCC) using a bispecific monoclonal antibody (bsMAb), which showed high tumor uptake of a radiolabeled peptide compared to other methods.

Optimal conditions for the pretargeting strategy were identified, with a 72-hour interval for the bsMAb IgG and a 4-hour interval for the bsMAb F(ab')(2), demonstrating that both forms of the bsMAb can achieve efficient tumor targeting without affecting the retention of the radiolabel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of IgG and F(ab')2 fragments of bispecific anti-RCCxanti-DTIn-1 antibody for pretargeting purposes. van Schaijk, FG., Boerman, OC., Soede, AC., et al.[2018]

The study demonstrated that pretargeting with the bispecific monoclonal antibody TF2 followed by the radiolabelled hapten peptide IMP288 allows for rapid and selective targeting of tumors in patients with metastatic colorectal cancer, achieving high tumor-to-tissue ratios within 24 hours.

The method was found to be safe, with high doses of (177)Lu-IMP288 being well tolerated, although some patients experienced manageable infusion reactions and transient thrombocytopenia, indicating a favorable safety profile for this innovative approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results. Schoffelen, R., Boerman, OC., Goldenberg, DM., et al.[2022]

In a phase I trial involving renal cell carcinoma patients, the bispecific monoclonal antibody BIS-1 demonstrated a maximum tolerated dose of 5 micrograms/kg, with acute but transient toxicity observed at higher doses.

Treatment with BIS-1 F(ab')2 fragments led to increased antitumor activity against EGP-2, particularly at the 3 and 5 micrograms/kg doses, suggesting a potential for enhanced immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific monoclonal antibodies for intravenous treatment of carcinoma patients: immunobiologic aspects. Kroesen, BJ., Janssen, RA., Buter, J., et al.[2016]

The novel bispecific antibody A2V CrossMab, targeting both Angiopoietin-2 and VEGF, significantly reduced tumor volume and vessel density in renal cell carcinoma compared to treatments targeting either factor alone.

A2V CrossMab also led to a significant down-regulation of angiogenesis-related genes, indicating its potential for enhanced anti-tumor efficacy in RCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Ang-2-VEGF-A Bispecific Antibody in Renal Cell Carcinoma. Bessho, H., Wong, B., Huang, D., et al.[2015]

The monoclonal antibody G250 shows preferential localization to renal-cell carcinoma (RCC) xenografts in mice, with 27.4% of the injected dose per gram found in tumors 24 hours after injection, indicating its potential effectiveness for targeting RCC.

Using F(ab')2 fragments of G250 resulted in higher tumor-to-blood ratios, suggesting that these smaller fragments may be more suitable for diagnostic purposes in patients, as tumor uptake is more influenced by size than binding affinity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localization of monoclonal antibody G250 and bispecific monoclonal antibody CD3/G250 in human renal-cell carcinoma xenografts: relative effects of size and affinity. van Dijk, J., Zegveld, ST., Fleuren, GJ., et al.[2019]

The bispecific antibody construct (bAb) targeting both CD3 and EGFR effectively induced significant cell lysis in EGFR-positive tumor cells at very low concentrations (1 ng/ml), demonstrating its potential efficacy in targeting cancer cells.

However, the bAb also caused lysis of normal cells expressing EGFR, indicating a need for careful consideration of safety in future clinical trials, as it may affect healthy tissues alongside tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of tumour cell lysis by a bispecific antibody recognising epidermal growth factor receptor (EGFR) and CD3. Knuth, A., Bernhard, H., Jäger, E., et al.[2019]

The bispecific monoclonal antibody OC/TR shows specific localization in Hela tumor xenografts in nude mice, indicating its potential for targeted cancer therapy despite having a lower affinity than the parental MOv18 antibody.

Although OC/TR has reduced tumor uptake compared to MOv18, it still meets the initial requirement for effective tumor targeting, suggesting it could be a promising therapeutic option, pending further investigation into its interaction with human T-cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour targeting of the anti-ovarian carcinoma x anti-CD3/TCR bispesific monoclonal antibody OC/TR and its parental MOv18 antibody in experimental ovarian cancer. Boerman, OC., Tibben, JG., Massuger, LF., et al.[2015]

Citations

1. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-presents-initial-data-xmab819-first-class-enpp3-x-cd3

Xencor Presents Initial Data for XmAb819, a First-in-class ... ... -- XmAb819 is well-tolerated in heavily pretreated patients with advanced ccRCC --. -- 25% overall response rate (ORR) observed within ...

2. finance.yahoo.com finance.yahoo.com/news/xencor-presents-initial-data-xmab819-163000598.html

Xencor Presents Initial Data for XmAb819, a First-in-class ... ... -- XmAb819 is well-tolerated in heavily pretreated patients with advanced ccRCC --. -- 25% overall response rate (ORR) observed within ...

3. aacrjournals.org aacrjournals.org/mct/article/24/10_Supplement/B006/766373/Abstract-B006-Preliminary-Phase-1-safety-and

Preliminary Phase 1 safety and antitumor activity of XmAb819 ... XmAb819 is a T-cell engaging bispecific antibody in development for patients with ccRCC. Despite advances in the treatment of metastatic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12509653/

A Phase 1, multiple-dose study to evaluate the safety and ... Despite advances in the treatment of metastatic ccRCC, few patients are cured. Therapies exploiting novel targets are needed.

5. onclive.com onclive.com/view/dual-binding-xmab30819-shows-strong-specificity-in-enpp3-positive-rcc

Dual-Binding XmAb30819 Shows Strong Specificity in ... A phase 1 study of XmAb819 (ENPP3 x CD3) in subjects with relapsed or refractory clear cell renal cell carcinoma (ccRCC). Presented at: Kidney ...

6. investors.xencor.com investors.xencor.com/static-files/94fd65d4-694d-498c-86d4-766340f5e4d1

Preliminary Phase 1 Safety and Antitumor Activity of ... XmAb819 is a T-cell engaging bispecific antibody in development for patients with ccRCC. • XmAb819 utilizes a multivalent 2+1 format with high-avidity bivalent ...

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

August 6, 2025-- Xencor, Inc. (NASDAQ:XNCR), a clinical- ... We are on-track to present preliminary safety and efficacy from XmAb819 in advanced clear cell renal cell carcinoma later this year.” “In our autoimmune ...