CBX-12 for Ovarian Cancer

Recruiting at 18 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

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety and effectiveness of a new treatment called CBX-12 (also known as alphalex™-exatecan) for women with ovarian cancer that does not respond to standard platinum-based therapies. The study compares two different doses of CBX-12 to determine which is more effective. Women with ovarian, fallopian tube, or primary peritoneum cancer, who have experienced a recurrence after at least one platinum-based treatment, might be suitable candidates. Participants will receive CBX-12 by IV infusion every 21 days until their cancer progresses or they experience severe side effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

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.

Is there any evidence suggesting that CBX-12 is likely to be safe for humans?

Research has shown that CBX-12 is well-tolerated in previous studies. It has a good safety record, with common side effects primarily affecting blood, such as low levels of certain blood cells. In trials involving various advanced cancers, patients generally tolerated CBX-12 well, and it proved effective. While some side effects occur, most people can manage them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about CBX-12 for treating ovarian cancer because it introduces a unique approach compared to standard treatments like chemotherapy and targeted therapies. Unlike these traditional options, CBX-12 uses a novel mechanism by delivering a potent drug directly to the cancer cells via intravenous infusion, potentially reducing side effects. The study explores two dosing regimens, 125mg/m² and 100mg/m² administered every 21 days, allowing researchers to optimize effectiveness while monitoring safety and tolerability. This targeted delivery system has the potential to enhance treatment precision and improve outcomes for patients with ovarian cancer.

What evidence suggests that CBX-12 might be an effective treatment for ovarian cancer?

Research has shown that CBX-12 may help treat ovarian cancer. In one study, CBX-12 proved effective for 40% of patients with ovarian cancer who hadn't tried a specific type of drug before. This finding is significant because it suggests CBX-12 could benefit those with limited treatment options. The treatment is generally well-tolerated, with fewer side effects. These results indicate that CBX-12 could be a promising option for individuals with difficult-to-treat ovarian cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Michael Needle, MD

Principal Investigator

Cybrexa Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. cybrexa.com cybrexa.com/press-release/cybrexa-therapeutics-announces-positive-final-data-at-esmo-2024-from-phase-1-study-of-peptide-drug-conjugate-cbx-12-in-advanced-solid-tumors/

Data demonstrate broad activity of CBX-12 ... Data demonstrate broad activity of CBX-12 across six tumor types with a strong response rate in TOP1-naïve patients with ovarian (40%; N=10) ...

2. synapse.patsnap.com synapse.patsnap.com/article/cybrexa-therapeutics-reports-positive-final-data-on-cbx-12-phase-1-study-at-esmo-2024

Cybrexa Therapeutics Reports Positive Final Data on CBX- ... The data revealed that CBX-12 is well tolerated and shows significant efficacy across different types of advanced or metastatic solid tumors, ...

3. cybrexa.com cybrexa.com/press-release/

Press Releases Archive - Cybrexa ... This trial builds upon promising Phase 1 data, which demonstrated broad activity across multiple tumor types, including ovarian, breast, non-small cell lung ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06315491

A Study of CBX 12 in Subjects With Platinum Resistant or ... 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 ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-ovarian-epithelial-6-2024-0c396

CBX-12 for Ovarian Cancer In a phase IIA study involving 57 patients with platinum- and taxane-resistant ovarian cancer, exatecan mesylate showed a modest radiological response rate of ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/472119

A Study of CBX 12 in Subjects With Platinum Resistant or ... 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 ...