CBX-12 for Ovarian Cancer

Recruiting at 19 trial locations

Overseen By Clinical Operations Trial Team

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Cybrexa Therapeutics

Must not be taking: Anticancer, Investigational agents

Disqualifiers: HIV, Hepatitis B/C, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

Duration: Up to 21 months

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticancer or investigational agents at least 3 weeks before starting the study medication. If you are on other types of medications, the protocol does not specify whether you need to stop them.

What data supports the effectiveness of the drug CBX-12 for ovarian cancer?

Research shows that CBX-12, when combined with certain immunotherapies, can delay tumor growth and lead to long-term immunity against tumors. Additionally, exatecan mesylate, a component of CBX-12, has shown potent activity against ovarian cancer in laboratory studies. ^{1 2 3 4 5}

What safety data exists for CBX-12 (alphalex™-exatecan) in humans?

CBX-12, also known as exatecan, has been studied in various clinical trials and has shown a favorable safety profile. Common side effects include blood-related issues like neutropenia (low white blood cell count) and thrombocytopenia (low platelet count), as well as moderate gastrointestinal issues such as nausea and vomiting. These side effects were generally dose-dependent and reversible. ^{1 2 6 7 8}

What makes the drug CBX-12 unique for treating ovarian cancer?

CBX-12 (alphalex™-exatecan) is unique because it is designed to specifically target cancer cells, potentially reducing side effects compared to traditional chemotherapy. This targeted approach may offer a novel mechanism of action compared to existing treatments for ovarian cancer. ^{3 9 10 11 12}

What is the purpose of this trial?

The purpose of this study is to assess the safety, tolerability, and efficacy of CBX-12 in female subjects with platinum resistant or refractory ovarian cancer at 2 doses; 125 mg/m2 every 21 days or 100 mg/m2 every 21 days.

Research Team

Michael Needle, MD

Principal Investigator

Cybrexa Therapeutics

Eligibility Criteria

This trial is for women aged 18 or older with ovarian cancer that's resistant to platinum-based chemotherapy. They must have tried only one such treatment for at least four cycles and seen their disease progress within 26 weeks after the last dose, or after a second course. Up to two other treatments are allowed, but maintenance therapies don't count.

Inclusion Criteria

I am fully active or can carry out light work.

I have had no more than 2 treatments for my advanced cancer, not counting maintenance therapy.

My cancer worsened during or within 6 months after platinum-based chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CBX-12 at either 125 mg/m2 or 100 mg/m2 every 21 days until disease progression or unacceptable toxicity

Up to 21 months

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post last dose

Treatment Details

Interventions

• CBX-12

Trial Overview The study tests CBX-12's safety and effectiveness in treating ovarian cancer that doesn't respond well to platinum drugs. Participants will receive either 125 mg/m2 or 100 mg/m2 of CBX-12 every three weeks to determine which dosage works better.

Participant Groups

Group I: CBX-12 - 125mg/m2 q21d Experimental Treatment 1 Intervention

125mg/m2 CBX-12 administered by intravenous (IV) infusion every 21 days. Treatment will continue until there is evidence of progressive disease (PD) or development of unacceptable toxicity.

Group II: CBX-12 - 100mg/m2 q21d Experimental Treatment 1 Intervention

100mg/m2 CBX-12 administered by intravenous (IV) infusion every 21 days. Treatment will continue until there is evidence of progressive disease (PD) or development of unacceptable toxicity.

Who Is Running the Clinical Trial?

Cybrexa Therapeutics

Lead Sponsor

Trials

2

Recruited

190+

Findings from Research

The pH-sensitive peptide CBX-12, when combined with the TOP1 inhibitor exatecan, significantly enhances the effectiveness of immunotherapy (anti-PD-1 and anti-CTLA4) in delaying tumor growth and achieving complete responses in a syngeneic CT26 model.

CBX-12 not only promotes the expression of important immune markers like MHC 1 and PD-L1 but also induces immunogenic cell death, leading to long-term antitumor immunity and immune recognition of tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-independent tumor targeting by CBX-12 (alphalex™-exatecan) induces long-term antitumor immunity. Gayle, S., Paradis, T., Jones, K., et al.[2023]

In a phase IIA study involving 57 patients with platinum- and taxane-resistant ovarian cancer, exatecan mesylate showed a modest radiological response rate of 5.3% when given daily, indicating limited efficacy as a single agent.

The treatment was generally well tolerated, but significant side effects included myelosuppression, with 29% of patients experiencing severe neutropenia and 71% requiring red cell transfusions, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIA study of the topoisomerase I inhibitor, exatecan mesylate (DX-8951f), administered at two different dose schedules in patients with platinum- and taxane-resistant/refractory ovarian cancer. Clamp, A., Adams, M., Atkinson, R., et al.[2017]

High levels of keratin 7 (KRT7) in ovarian cancer patients are associated with poorer progression-free and overall survival, suggesting it could serve as a prognostic biomarker.

KRT7 expression is linked to immune cell infiltration and is notably elevated in paclitaxel-resistant ovarian cancer cell lines, indicating its potential as a target for new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of the KRT7 Biomarker in Immune Infiltration and Paclitaxel Resistance in Ovarian. Wang, S., Li, H., Li, M., et al.[2023]

DX-8951f, a new derivative of camptothecin, demonstrated greater potency than both SN-38 and topotecan in inhibiting the growth of human colon and ovarian cancer cell lines, indicating its potential as a more effective treatment option.

In vivo studies showed that DX-8951f significantly inhibited tumor growth in human ovarian cancer xenografts, especially when combined with cisplatin or paclitaxel, suggesting that this combination could enhance therapeutic outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The activity profile of the hexacyclic camptothecin derivative DX-8951f in experimental human colon cancer and ovarian cancer. van Hattum, AH., Pinedo, HM., Schlüper, HM., et al.[2019]

Inhibiting Src family and Abl kinases using siRNAs or dasatinib significantly enhances the sensitivity of ovarian cancer cells to paclitaxel, as demonstrated in both cell cultures and HEY xenograft models.

The mechanism involves the induction of p27(Kip1), which promotes apoptosis by suppressing Bcl-2 and Cdk1 expression, leading to increased effectiveness of paclitaxel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. Le, XF., Mao, W., He, G., et al.[2021]

Exatecan mesylate (DX-8951f) shows promising antitumor activity against various solid tumors, including those resistant to other treatments like CPT-11 and topotecan, based on results from multiple phase I clinical trials.

The drug has a manageable safety profile, with dose-dependent hematologic toxicity being the main concern, particularly neutropenia, which was reversible and dose-limiting in patients with different treatment histories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DX-8951f: summary of phase I clinical trials. De Jager, R., Cheverton, P., Tamanoi, K., et al.[2019]

Belotecan (CKD-602) demonstrated an overall response rate of 30.2% in treating recurrent or refractory epithelial ovarian cancer, with a median progression-free survival of 6.5 months, indicating its efficacy as a single-agent chemotherapy.

The most common side effect was hematologic toxicity, which was found to be tolerable, suggesting that belotecan has an acceptable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and toxicity of belotecan (CKD-602), a camptothericin analogue topoisomerase I inhibitor, in patients with recurrent or refractory epithelial ovarian cancer. Kim, YM., Lee, SW., Kim, DY., et al.[2013]

In a phase II study involving 42 patients with advanced cholangiocarcinoma and gallbladder carcinoma, exatecan showed minimal antitumor activity, with only 4.9% of patients achieving a partial response and 51.2% experiencing disease progression.

The treatment was associated with manageable toxicity, primarily grade 3/4 neutropenia, and resulted in a median overall survival of 7 months, with 6-month and 12-month survival rates of 56.1% and 31.7%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers. Abou-Alfa, GK., Rowinsky, EK., Patt, YZ., et al.[2019]

The Access OV Monitor Immunoassay System shows excellent analytical performance with low imprecision and high reproducibility, making it a reliable tool for measuring CA125 levels in patients, which is crucial for managing ovarian cancer.

In a study involving 1811 individuals, the OV Monitor demonstrated a strong correlation with the Elecsys CA125 system and provided optimal diagnostic accuracy for detecting ovarian cancer, with an area under the curve (AUC) of 0.898, indicating its effectiveness in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative antibody for the detection of CA125 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access OV Monitor assay on the UniCel Dxl 800 Immunoassay System. Holdenrieder, S., Molina, R., Gion, M., et al.[2019]

In a study of 205 primary ovarian cancer specimens, 18% showed moderate to strong expression of carbonic anhydrase IX (CAIX), particularly in mucinous and endometrioid types, indicating its potential role in cancer progression.

High CAIX expression was associated with poorer patient survival and was identified as an independent prognostic marker, suggesting that targeting CAIX could be a promising therapeutic strategy for advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of carbonic anhydrase IX (CAIX) is an independent unfavorable prognostic marker in endometrioid ovarian cancer. Choschzick, M., Oosterwijk, E., Müller, V., et al.[2021]

CA125-targeted antibody maintenance therapy for advanced epithelial ovarian cancer did not show improved overall survival or progression-free survival compared to placebo, based on a meta-analysis of four trials involving 1,259 women.

The treatment was found to be safe, with toxicity levels similar to those of placebo, indicating that while it may not enhance survival, it does not pose additional risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antibody-based CA125-targeted maintenance therapy for the epithelial ovarian cancer: a meta-analysis. Mei, L., Hou, Q., Fang, F., et al.[2020]

The monoclonal antibody OvaRex MAb-B43.13, which targets the CA125 antigen associated with ovarian cancer, has shown promising therapeutic effects in a human-PBL-SCID/BG mouse model, including delaying tumor development and prolonging survival.

In experiments, OvaRex MAb-B43.13 not only reduced the size of established tumors but also suppressed ascites formation, indicating its potential effectiveness in treating ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of human ovarian carcinoma with OvaRex MAb-B43.13 in a human-PBL-SCID/BG mouse model. Schultes, BC., Zhang, C., Xue, LY., et al.[2019]

References

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

Antigen-independent tumor targeting by CBX-12 (alphalex™-exatecan) induces long-term antitumor immunity. [2023]

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

A phase IIA study of the topoisomerase I inhibitor, exatecan mesylate (DX-8951f), administered at two different dose schedules in patients with platinum- and taxane-resistant/refractory ovarian cancer. [2017]

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

Role of the KRT7 Biomarker in Immune Infiltration and Paclitaxel Resistance in Ovarian. [2023]

4. England pubmed.ncbi.nlm.nih.gov

The activity profile of the hexacyclic camptothecin derivative DX-8951f in experimental human colon cancer and ovarian cancer. [2019]

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

The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. [2021]

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

DX-8951f: summary of phase I clinical trials. [2019]

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

The efficacy and toxicity of belotecan (CKD-602), a camptothericin analogue topoisomerase I inhibitor, in patients with recurrent or refractory epithelial ovarian cancer. [2013]

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

A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Alternative antibody for the detection of CA125 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access OV Monitor assay on the UniCel Dxl 800 Immunoassay System. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Overexpression of carbonic anhydrase IX (CAIX) is an independent unfavorable prognostic marker in endometrioid ovarian cancer. [2021]

11. Singapore pubmed.ncbi.nlm.nih.gov

The antibody-based CA125-targeted maintenance therapy for the epithelial ovarian cancer: a meta-analysis. [2020]

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

Immunotherapy of human ovarian carcinoma with OvaRex MAb-B43.13 in a human-PBL-SCID/BG mouse model. [2019]