CBX-12 for Cancer

Recruiting in New Haven (>99 mi)

+3 other locations

Overseen By Anthony Tolcher, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Cybrexa Therapeutics

Must not be taking: Cytotoxic chemotherapy, Biologic agents

Disqualifiers: CNS tumors, Active CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain cancer treatments before starting CBX-12. Specifically, you must stop cytotoxic chemotherapy, biologic agents, investigational agents, or radiation therapy at least 3 weeks before, and small-molecule kinase inhibitors or hormonal agents at least 14 days before the first dose of CBX-12.

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

Irinotecan, a component similar to CBX-12, has shown significant activity in treating non-small-cell lung cancer (NSCLC) when used alone or in combination with other drugs, suggesting potential effectiveness in cancer treatment. ^{1 2 3 4 5}

What makes the drug CBX-12 unique for cancer treatment?

CBX-12, also known as 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 improve the drug's effectiveness and safety profile. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial tests a new drug called CBX-12 on patients with advanced tumors that haven't responded to other treatments. The goal is to find the safest and most effective dose by trying different schedules.

Research Team

Chief Medical Officer

Principal Investigator

Cybrexa Therapeutics

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors that have worsened after treatment, or when no approved therapy exists. Participants must have measurable disease and provide tumor samples. They can't join if they've had certain treatments within 3 weeks (2 weeks for some cases) before starting the study, are on other cancer treatments, have significant diseases, or active brain metastases without approval.

Inclusion Criteria

I agree to a biopsy of the same lesion as before, if it's safe.

My advanced cancer has worsened after treatment, or no approved treatment exists for it.

I have a recent tumor sample from a needle biopsy.

Exclusion Criteria

I haven't taken any small-molecule kinase inhibitors or hormonal agents in the last 14 days.

I have brain metastases but they are stable, or I have approval to join.

I have a serious health condition besides cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Safety and tolerability of CBX-12 are evaluated across different dosing schedules

15 months

Multiple visits as per dosing schedule

Phase 2 Expansion

Expansion cohorts for metastatic breast and ovarian cancer to evaluate efficacy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• CBX-12

Trial Overview CBX-12 is being tested in this Phase 1/2 trial to evaluate its safety and how it affects the body (pharmacokinetics). It's an open-label study where everyone gets CBX-12; there's a dose-escalation phase to find the right amount of drug that's safe and potentially effective.

Participant Groups

Group I: Phase 2 Ovarian Cancer Expansion Cohort Experimental Treatment 1 Intervention

CBX-12 administered TBD

Group II: Phase 2 Metastatic Breast Expansion Cohort Experimental Treatment 1 Intervention

CBX-12 administered TBD

Group III: Phase 1 Schedule C Dose Escalation (Once Weekly Dosing ) Experimental Treatment 1 Intervention

CBX-12 administered once weekly, 4 week schedule

Group IV: Phase 1 Schedule B Dose Escalation (Daily Dosing x 3) Experimental Treatment 1 Intervention

CBX-12 administered on a daily x 3, 3 week schedule

Group V: Phase 1 Schedule A Dose Escalation (Daily Dosing x 5) Experimental Treatment 1 Intervention

CBX-12 administered on a daily x 5, 3 week schedule

Group VI: Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks) Experimental Treatment 1 Intervention

CBX-12 administered once every 3 weeks

Who Is Running the Clinical Trial?

Cybrexa Therapeutics

Lead Sponsor

Trials

2

Recruited

190+

Findings from Research

In a study of 27 patients with advanced non-small-cell lung cancer, the combination of carboplatin and nanoparticle albumin-bound paclitaxel showed an overall response rate of 37% and a median overall survival of 11.4 months, indicating its efficacy as a treatment option.

The treatment was found to be safe, with no treatment-related deaths and only a small percentage of patients experiencing significant toxicity, although caution is advised due to the occurrence of interstitial lung disease in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Carboplatin/Nanoparticle Albumin-Bound Paclitaxel Combination Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer or Recurrent Non-Small-Cell Lung Cancer Following Surgery]. Shimabukuro, I., Noguchi, S., Uyama, K., et al.[2018]

In a phase I trial involving 14 patients with advanced refractory cancers, PX-12 was found to be safe and tolerable at a dose of 400 mg/m²/day, with common mild side effects like fatigue and taste alteration.

The trial identified dose-limiting toxicities, including grade 3 hypoxia and reversible pneumonitis at higher doses, but the best response observed was stable disease in one patient, suggesting that further evaluation of thioredoxin inhibition as a treatment strategy is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of PX-12, a small-molecule inhibitor of thioredoxin-1, administered as a 72-hour infusion every 21 days in patients with advanced cancers refractory to standard therapy. Ramanathan, RK., Stephenson, JJ., Weiss, GJ., et al.[2021]

In a study of 72 patients with advanced non-small cell lung cancer, the combination of bevacizumab and pemetrexed resulted in a significantly longer overall survival time of 14 months compared to 11 months for those receiving only pemetrexed.

While the combination therapy showed improved overall response and disease control rates, these differences were not statistically significant, indicating that while the combination may enhance survival, it does not drastically change response rates compared to pemetrexed alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer. Zhang, YM., Li, YQ., Liu, ZH., et al.[2022]

PGG-PTX, a new formulation of paclitaxel, showed superior tumor growth inhibition compared to Abraxane in mouse models of lung, ovarian, and melanoma cancers, particularly with single doses.

While PGG-PTX was about 1.5-fold less potent than Abraxane, it caused significantly less weight loss in mice, indicating a better safety profile while effectively enhancing drug delivery to tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane. Feng, Z., Zhao, G., Yu, L., et al.[2021]

The thermosensitive micelles-hydrogel hybrid system (PTX-M-MG) demonstrated improved drug loading and release characteristics, leading to a prolonged retention of the drug paclitaxel at tumor sites for up to 20 days.

In vivo studies showed that PTX-M-MG achieved a tumor inhibition rate of 64.27% with reduced toxicity compared to traditional treatments, indicating its potential as an effective local delivery system for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thermosensitive micelles-hydrogel hybrid system based on poloxamer 407 for localized delivery of paclitaxel. Ju, C., Sun, J., Zi, P., et al.[2022]

References

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

Irinotecan in non-small-cell lung cancer: status of ongoing trials. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Carboplatin/Nanoparticle Albumin-Bound Paclitaxel Combination Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer or Recurrent Non-Small-Cell Lung Cancer Following Surgery]. [2018]

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

A phase I trial of PX-12, a small-molecule inhibitor of thioredoxin-1, administered as a 72-hour infusion every 21 days in patients with advanced cancers refractory to standard therapy. [2021]

4. Thailand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer. [2022]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Pre-clinical study of combined aranosa, cisplatin and irinotecan in the treatment of experimental lung cancer]. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane. [2021]

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

Novel amphiphilic folic acid-cholesterol-chitosan micelles for paclitaxel delivery. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Paclitaxel-Loaded β-Cyclodextrin-Modified Poly(Acrylic Acid) Nanoparticles through Multivalent Inclusion for Anticancer Therapy. [2016]

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

Thermosensitive micelles-hydrogel hybrid system based on poloxamer 407 for localized delivery of paclitaxel. [2022]

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

Conjugated chitosan as a novel platform for oral delivery of paclitaxel. [2022]