CBP-1019 Combinations for Cancer

Overseen By Siqing Fu, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Steroids, Immunosuppressants, others

Disqualifiers: Infections, Heart failure, Stroke, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Dose escalation and expansion phases

128 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) required for some prior treatments before starting the trial. It's best to discuss your current medications with the trial team to understand any necessary adjustments.

What data supports the effectiveness of the drug CBP-1019?

Research on similar folate-targeted drug conjugates, like EC1456 and EC131, shows they can effectively target and kill cancer cells that have high levels of folate receptors, which are common in many types of cancer. These studies suggest that CBP-1019, which also uses folate targeting, might work similarly by delivering its cancer-fighting components directly to the tumor cells. ^{1 2 3 4 5}

What safety data exists for CBP-1019 or similar treatments?

The research articles provided do not contain specific safety data for CBP-1019 or its related names. They discuss other folate-drug conjugates and their safety profiles, but not CBP-1019 specifically. ^{1 2 4 6 7}

What makes the drug CBP-1019 unique compared to other cancer treatments?

CBP-1019 is unique because it is a folate-TRPV6-peptide exatecan drug conjugate, which targets cancer cells that overexpress folate receptors, allowing for more precise delivery of the drug to cancer cells while minimizing effects on normal cells. This targeted approach is similar to other folate-linked therapies but uses a novel combination of components to enhance specificity and efficacy. ^{1 2 3 4 5}

What is the purpose of this trial?

An open-label, Phase Ib dose escalation and dose expansion clinical trial evaluating the safety and efficacy of CBP-1019 combinations in patients with solid tumors of epithelial origin.

Research Team

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with solid tumors of epithelial origin that overexpress TRPV6. It's open to those who meet specific health criteria, but the details on eligibility are not provided here.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

Ability to understand and the willingness to sign a written informed consent document.

The effects of study drugs on the developing human fetus are unknown. Women of childbearing potential must agree to use adequate contraception prior to study entry, throughout the study treatment period, and for 6 months after study treatment completion.

Exclusion Criteria

My brain cancer symptoms are not controlled by medication, or I need high doses of steroids.

My cancer has spread to the lining of my brain or spinal cord, or to my lymph system.

I can take pills and do not have chronic stomach or absorption problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CBP-1019 in combination with FOLFOX, Bevacizumab, Pembrolizumab, or Enzalutamide for metastatic solid tumors of epithelial origin

Dose escalation and expansion phases

Outpatient basis

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• CBP-1019

Trial Overview The study tests CBP-1019 in combination with FOLFOX (a chemo regimen including Leucovorin, Oxaliplatin, and 5-FLUOROURACIL) and may add Bevacizumab, Pembrolizumab or Enzalutamide. The goal is to find safe doses and see how well these combinations work.

Participant Groups

Group I: Part 2D: CRPC CBP-1019 + Enzalutamide Experimental Treatment 2 Interventions

Participants will be administered the study treatments on an outpatient basis.

Group II: Part 2C: Epithelial Origin CBP-1019 + Pembrolizumab Experimental Treatment 2 Interventions

Participants will be administered the study treatments on an outpatient basis.

Group III: Part 2B: Colorectal CBP-1019 + FOLFOX + Bevacizumab Experimental Treatment 5 Interventions

Participants will be administered the study treatments on an outpatient basis.

Group IV: Part 2A: Pancreatic CBP-1019 + FOLFOX Experimental Treatment 4 Interventions

Participants will be administered the study treatments on an outpatient basis.

Group V: Part 1D: Dose Escalation CBP-1019 + Enzalutamide Experimental Treatment 2 Interventions

Participants will be administered the study treatments on an outpatient basis.

Group VI: Part 1C: Dose Escalation CBP-1019 + Pembrolizumab Experimental Treatment 2 Interventions

Participants will be administered the study treatments on an outpatient basis.

Group VII: Part 1B: Dose Escalation CBP-1019 + FOLFOX + Bevacizumab Experimental Treatment 5 Interventions

Participants will be administered the study treatments on an outpatient basis.

Group VIII: Part 1A: Dose Escalation CBP-1019 + FOLFOX Experimental Treatment 4 Interventions

Participants will be administered the study treatments on an outpatient basis.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

EC1456 is a highly specific folate-tubulysin conjugate that shows approximately 1000-fold specificity against folate receptor-positive cancer cells, demonstrating effective dose-responsive activity in preclinical models.

In studies with nude mice bearing FR-positive human tumors, EC1456 not only cured 100% of the mice at non-toxic doses but also enhanced the effectiveness of standard chemotherapy agents, suggesting its potential as a powerful treatment option for resistant cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical evaluation of EC1456, a folate-tubulysin anti-cancer therapeutic. Reddy, JA., Dorton, R., Bloomfield, A., et al.[2019]

EC131, a folate receptor-targeted drug conjugate, demonstrated high specificity and potency against FR-positive cancer cells, with an IC(50) in the low nanomolar range, and showed significant antitumor efficacy in mouse models without causing systemic toxicity.

The therapeutic effect of EC131 was completely blocked by excess free folic acid, confirming its targeted action, while conventional maytansinoid DM1 was ineffective at its maximum tolerated dose, highlighting EC131's superior efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folate receptor-specific antitumor activity of EC131, a folate-maytansinoid conjugate. Reddy, JA., Westrick, E., Santhapuram, HK., et al.[2021]

Folic acid (FA) can effectively target folate receptors (FRs) that are often overexpressed in various cancer cells, making it a promising tool for delivering anticancer drugs like methotrexate (MTX).

The new FA-AG-GFLG-MTX drug conjugate showed a 6.3-fold increase in cytotoxic activity against FR-overexpressing cancer cells compared to those lacking FR, demonstrating its potential for targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arabinogalactan-folic acid-drug conjugate for targeted delivery and target-activated release of anticancer drugs to folate receptor-overexpressing cells. Pinhassi, RI., Assaraf, YG., Farber, S., et al.[2016]

The study developed targeted drug delivery systems using cyclic cell-penetrating peptides (cCPP) conjugated with cabazitaxel (CBT), which showed significantly reduced toxicity to normal cells while maintaining efficacy against cancer cells that overexpress specific biomarkers.

Conjugates targeting integrin and extra domain B of fibronectin demonstrated selective efficacy and stability in various conditions, suggesting that this approach can enhance the effectiveness of chemotherapy while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Delivery of Cabazitaxel Using Cyclic Cell-Penetrating Peptide and Biomarkers of Extracellular Matrix for Prostate and Breast Cancer Therapy. Park, SE., El-Sayed, NS., Shamloo, K., et al.[2021]

Eight new drug conjugates combining a camptothecin derivative (Namitecan) with RGD peptides were developed to enhance drug delivery to tumors, focusing on optimizing the drug-linkage for better performance.

Among the tested conjugates, C6 and C7 demonstrated strong receptor affinity, good stability in blood, and high cytotoxicity against tumor cells, with an IC₅₀ of 8 nM, indicating their potential as effective cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjugates of a novel 7-substituted camptothecin with RGD-peptides as α(v)β₃ integrin ligands: An approach to tumor-targeted therapy. Dal Pozzo, A., Esposito, E., Ni, M., et al.[2017]

The novel folate-taxoid conjugate 1, designed using bioorthogonal 'click' chemistry, shows exceptional potency against cancer cells (IC₅₀ 2.1-3.5 nM) while being over 1000 times less toxic to normal human cells (IC₅₀ >5000 nM).

The high selectivity and effectiveness of conjugate 1 are due to its ability to specifically target folate receptors on cancer cells and efficiently release the active drug through a self-immolative linker mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, synthesis and biological evaluation of a highly-potent and cancer cell selective folate-taxoid conjugate. Seitz, JD., Vineberg, JG., Herlihy, E., et al.[2018]

A new series of zinc(II) dipicolylamine (ZnDPA)-based drug conjugates were developed, showing that phosphatidylserine (PS) can be effectively targeted for small molecule drug conjugate (SMDC) therapies.

One specific conjugate (conjugate 24) demonstrated significant tumor regression in a COLO 205 xenograft model, achieving a 70% reduction in cytotoxic payload compared to the standard drug irinotecan, indicating its potential for more effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates. Liu, YW., Shia, KS., Wu, CH., et al.[2017]

References

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

Pre-clinical evaluation of EC1456, a folate-tubulysin anti-cancer therapeutic. [2019]

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

Folate receptor-specific antitumor activity of EC131, a folate-maytansinoid conjugate. [2021]

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

Arabinogalactan-folic acid-drug conjugate for targeted delivery and target-activated release of anticancer drugs to folate receptor-overexpressing cells. [2016]

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

Targeted Delivery of Cabazitaxel Using Cyclic Cell-Penetrating Peptide and Biomarkers of Extracellular Matrix for Prostate and Breast Cancer Therapy. [2021]

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

Conjugates of a novel 7-substituted camptothecin with RGD-peptides as α(v)β₃ integrin ligands: An approach to tumor-targeted therapy. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Design, synthesis and biological evaluation of a highly-potent and cancer cell selective folate-taxoid conjugate. [2018]

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

Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates. [2017]