CX-2051 for Advanced Cancer

Recruiting at 3 trial locations

Overseen By Karen Deane

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: CytomX Therapeutics

Must not be taking: Anticancer, Radiotherapy, ADCs

Disqualifiers: CNS involvement, Recent cancers, others

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

Compensation: Varies

Number of Visits: Unknown

124 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this first-in-human study, CTMX-2051-101, is to characterize the safety, tolerability, and antitumor activity of CX-2051 in adult participants with advanced solid tumors.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic anticancer treatments, radiotherapy, or investigational agents at least 14 days before starting the study treatment.

What data supports the effectiveness of the drug CX-2051 for advanced cancer?

The research highlights that EpCAM, a target for cancer therapy, is involved in tumor progression and is used in treatments like catumaxomab, which has shown some effectiveness in prolonging survival in certain cancer patients. This suggests that targeting EpCAM, as CX-2051 does, could potentially be effective in treating advanced cancer. ^{1 2 3 4 5}

What safety data exists for CX-2051 (EpCAM PROBODY ADC) in humans?

Some studies on treatments targeting EpCAM, like monoclonal antibodies, have shown well-tolerated side effects in cancer patients, but severe pancreatitis (inflammation of the pancreas) was noted with certain humanized antibodies. This suggests that while some EpCAM-targeted treatments are generally safe, others may have serious side effects. ^{4 6 7 8 9}

What makes the drug CX-2051 unique for treating advanced cancer?

CX-2051 is unique because it targets the epithelial cell adhesion molecule (EpCAM), which is often overexpressed in many cancers, allowing it to specifically attack cancer cells while sparing normal cells. This targeted approach may offer a more precise treatment option compared to traditional therapies that affect both healthy and cancerous cells. ^{2 9 10 11 12}

Research Team

Monika Vainorius, MD

Principal Investigator

CytomX Therapeutics

Eligibility Criteria

This trial is for adults with advanced solid tumors who have not responded to standard treatments. Specific eligibility details are not provided, but typically participants must be in good overall health aside from their cancer and able to comply with study requirements.

Inclusion Criteria

Measurable disease per RECIST v1.1

Consent to fresh biopsy or if medically contraindicated, recent (within 6 months) archival tumor tissue

Additional inclusion criteria may apply

Exclusion Criteria

I have not had major surgery in the last 4 weeks.

Elevated baseline laboratory values

Serious concurrent illness

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 involves CX-2051 dose escalation to identify the maximum tolerated dose (MTD) of CX-2051

44 months

Dose Expansion

Part 2 will further assess safety and tolerability as well as preliminarily assess antitumor activity of CX-2051 in indication-specific expansion cohorts

44 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Treatment Details

Interventions

• CX-2051

Trial Overview The trial is testing CX-2051, a new potential treatment for solid tumors. As it's the first time this drug is being used in humans, the focus will be on assessing its safety, how well patients tolerate it, and any signs of effectiveness against the tumors.

Participant Groups

Group I: CX-2051 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

CytomX Therapeutics

Lead Sponsor

Trials

9

Recruited

1,000+

Findings from Research

In a study of 109 patients with metastatic breast cancer, high-dose adecatumumab (6 mg/kg) significantly reduced the probability of tumor progression in patients with high levels of EpCAM expression compared to low-dose (2 mg/kg) treatment, indicating a dose-dependent effect.

Despite no confirmed tumor responses, the treatment was associated with notable adverse events, such as chills and nausea, highlighting the need for further research on adecatumumab in patients with EpCAM-overexpressing tumors and lower tumor burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Schmidt, M., Scheulen, ME., Dittrich, C., et al.[2021]

The study developed a [99mTc]Tc-labeled nanobody specifically targeting EpCAM, which showed high specificity for EpCAM-positive tumors in both in vitro and in vivo models, indicating its potential for accurate cancer imaging.

SPECT/CT imaging with [99mTc]Tc-NB4 allowed for clear visualization of tumors and tumor-draining lymph nodes, demonstrating its effectiveness as a noninvasive tool for monitoring EpCAM expression in epithelial-derived cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT. Liu, T., Wu, Y., Shi, L., et al.[2022]

In a case study of a 78-year-old patient with metastasized colorectal cancer, treatment with catumaxomab led to a puncture-free survival of 12 months, significantly improving the patient's quality of life by managing malignant ascites.

The treatment not only addressed local symptoms but also resulted in the regression of a pulmonary metastasis, suggesting that catumaxomab may have systemic antitumor effects beyond its primary use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic effect of catumaxomab in a patient with metastasized colorectal cancer: a case report. Bezan, A., Hohla, F., Meissnitzer, T., et al.[2021]

About one third of both colon cancer patients and tumor-free individuals had detectable levels of anti-EpCAM IgG antibodies, indicating that Ep-CAM is immunogenic in both groups.

Despite the presence of these antibodies, the study found that a specific monoclonal anti-EpCAM antibody did not provide any tumor-protective effect in a mouse model of colon cancer, suggesting that simply having these antibodies may not translate to effective cancer protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naturally occurring antibodies to epithelial cell adhesion molecule (EpCAM). Kirman, I., Jenkins, D., Fowler, R., et al.[2019]

In a study of 66 patients treated with the cancer therapy catumaxomab, the presence of soluble EpCAM (sEpCAM) in ascites was found to be a significant predictor of shorter overall survival, especially in ovarian cancer patients.

Only 13.6% of the patients tested positive for sEpCAM, suggesting that identifying this marker could help select patients who may not benefit from catumaxomab, highlighting the need for further research with larger sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab. Seeber, A., Braicu, I., Untergasser, G., et al.[2018]

A transgenic mouse model expressing human EpCAM was developed to study the effects of different anti-EpCAM monoclonal antibodies (mAbs), revealing that the design of these antibodies significantly impacts their behavior in vivo.

The fully human mAb UBS54 and the mouse-derived mAb MOC31 showed similar pharmacokinetics and tissue distribution, while the humanized mAb MOC31-hFc demonstrated limited uptake in normal tissues and slower blood clearance, suggesting that careful engineering of mAbs is crucial for their effectiveness in treating cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution studies of epithelial cell adhesion molecule (EpCAM)-directed monoclonal antibodies in the EpCAM-transgenic mouse tumor model. Kosterink, JG., McLaughlin, PM., Lub-de Hooge, MN., et al.[2019]

ING-1 and 3622W94 antibodies showed much higher binding affinity to EpCAM compared to adecatumumab and edrecolomab, which may explain their increased potency in killing cancer cells through immune mechanisms.

Adecatumumab demonstrated a larger therapeutic window in patients, likely due to its moderate binding affinity and unique epitope recognition, which resulted in less severe side effects like acute pancreatitis seen with the higher-affinity antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies. Münz, M., Murr, A., Kvesic, M., et al.[2021]

In a study involving 23 women with recurrent malignant ascites due to ovarian cancer, intraperitoneal (i.p.) treatment with the trifunctional antibody catumaxomab significantly reduced the flow rate of ascites and eliminated up to 5 log of EpCAM-positive tumor cells, indicating its efficacy in targeting cancer cells.

The treatment was generally well-tolerated, with most side effects being mild to moderate (grade 1 or 2), and most adverse events were reversible, suggesting that catumaxomab has an acceptable safety profile for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Burges, A., Wimberger, P., Kümper, C., et al.[2020]

This study successfully isolated four anti-EpCAM nanobodies from a large immune library, demonstrating strong binding affinity to EpCAM, which is important in cancer development.

Nanobodies Nb4 and Nb5 not only inhibited the growth of MCF-7 cancer cells in vitro but also significantly reduced tumor size in vivo after 14 days, suggesting their potential as effective therapeutic agents for cancers that overexpress EpCAM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and characterization of nanobodies against epithelial cell adhesion molecule as novel theranostic agents for cancer therapy. Roshan, R., Naderi, S., Behdani, M., et al.[2021]

The designed ankyrin repeats protein (DARPin) Ec1, labeled with a non-residualizing radioactive label, shows high specificity and affinity for EpCAM in ovarian carcinoma, making it a potential imaging diagnostic tool for patient stratification in targeted therapies.

In animal studies, [125I]I-PIB-Ec1 demonstrated excellent tumor-to-blood ratios and high contrast for ovarian tumors, indicating its effectiveness in visualizing EpCAM expression and supporting its use in future therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1. Vorobyeva, A., Konovalova, E., Xu, T., et al.[2021]

The novel fully human antibody MT201 effectively targets and eliminates ovarian cancer cells, showing significant cytotoxic activity at very low concentrations (sub-micro g/ml) in laboratory settings.

In a study involving 21 patients with ovarian cancer, MT201 demonstrated an impressive ex vivo response rate of 81%, with up to 80% lysis of tumor cells observed, indicating its potential as a promising therapy for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic activity of novel human monoclonal antibody MT201 against primary ovarian tumor cells. Xiang, W., Wimberger, P., Dreier, T., et al.[2019]

Adecatumumab was well tolerated in a phase I trial involving 20 patients with hormone refractory prostate cancer, showing a benign safety profile with no maximum tolerated dose reached and mostly mild to moderate adverse events.

The treatment resulted in significant transient increases in TNF-alpha levels and declines in natural killer cells, indicating potential immune modulation, while its long serum half-life of 15 days and low immunogenicity suggest it may be a promising option for targeting EpCAM-expressing cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study with adecatumumab, a human antibody directed against epithelial cell adhesion molecule, in hormone refractory prostate cancer patients. Oberneder, R., Weckermann, D., Ebner, B., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Systemic effect of catumaxomab in a patient with metastasized colorectal cancer: a case report. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Naturally occurring antibodies to epithelial cell adhesion molecule (EpCAM). [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Biodistribution studies of epithelial cell adhesion molecule (EpCAM)-directed monoclonal antibodies in the EpCAM-transgenic mouse tumor model. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Isolation and characterization of nanobodies against epithelial cell adhesion molecule as novel theranostic agents for cancer therapy. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

Cytotoxic activity of novel human monoclonal antibody MT201 against primary ovarian tumor cells. [2019]

12. England pubmed.ncbi.nlm.nih.gov

A phase I study with adecatumumab, a human antibody directed against epithelial cell adhesion molecule, in hormone refractory prostate cancer patients. [2019]