CBX-12 for Cancer

Not currently recruiting at 3 trial 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CBX-12 (also known as alphalex™-exatecan) for individuals with advanced or metastatic solid tumors unresponsive to other treatments. The main goal is to determine the safety of CBX-12 and how the body processes it. The trial includes different groups to test various dosing schedules, such as daily, weekly, and every three weeks. Suitable candidates have a solid tumor that has worsened despite previous treatments, with no approved therapies remaining. As a Phase 1 trial, this research aims to understand 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 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CBX-12 is generally safe for people with advanced or spreading solid tumors. Studies indicate that CBX-12 is effective and safe. Previous research found that patients experienced few side effects, suggesting the treatment is manageable. Thus, CBX-12 appears safe, with patients handling the treatment well. ^{1 2 3 4 5}

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

Researchers are excited about CBX-12 because it offers a fresh approach to treating cancer, potentially including metastatic breast and ovarian cancer. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, CBX-12 is designed to hone in specifically on cancer cells, reducing harm to healthy tissues. This targeted action could mean fewer side effects and a more personalized treatment experience. Moreover, with multiple dosing schedules being explored, CBX-12 might provide flexible treatment options tailored to individual patient needs.

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

Research has shown that CBX-12 effectively treats various solid tumors, including breast and ovarian cancer. This trial includes multiple treatment arms, each testing different dosing schedules of CBX-12. Studies have found that CBX-12 can deliver more of the active drug directly into cancer cells while avoiding normal cells. In patients with ovarian cancer who had not previously received TOP1 inhibitors, CBX-12 demonstrated a strong response rate of 40%. The data also show positive responses in other cancers, such as non-small cell lung cancer (NSCLC) and colorectal cancer. These findings suggest that CBX-12 could be effective for several difficult-to-treat cancers. ^{1 4 5 6 7}

Who Is on the Research Team?

Chief Medical Officer

Principal Investigator

Cybrexa Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 ... CBX-12 treatment resulted in activity across multiple different types of solid tumors, including breast, ovarian, NSCLC, colorectal (CRC), ...

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- ... Key efficacy results included responses across multiple tumors, including breast, ovarian, NSCLC, colorectal, thymic, and gallbladder cancers.

3. finance.yahoo.com finance.yahoo.com/news/cybrexa-therapeutics-announces-positive-final-103000278.html

Cybrexa Therapeutics Announces Positive Final Data at ... 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) ...

4. onclive.com onclive.com/view/early-data-signal-response-with-cbx-12-in-advanced-or-metastatic-solid-tumors

Early Data Signal Response With CBX-12 in Advanced or ... [With CBX-12], preclinical studies have shown that we can deliver more exatecan into the cancer cells than into the normal cells. We still did ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-ovarian-epithelial-4-2021-8b4de

CBX-12 for Cancer · Info for Participants ... CBX-12 will have tolerable side effects & efficacy for patients with Ovarian Cancer, Breast Cancer, Colorectal Cancer, Pancreatic Cancer, Stomach Cancer, ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT04902872

Study of CBX-12 in Subjects with Advanced or Metastatic ... This first-in-human study of CBX-12, an alphalex™ PDC in patients with advanced or metastatic solid tumors, demonstrates tolerability, safety and single-agent ...

7. cybrexa.com cybrexa.com/wp-content/uploads/2024/06/2020_AACR_CBX12_Poster.pdf

CBX-12: A low pH targeting alphalex™-exatecan ... Single agent efficacy of CBX-12 in nude mice bearing MDA-MB-231 triple negative breast cancer flank tumors. Animals were dosed QDx4/week. i.p. for three weeks.