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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new cancer treatment, CBP-1019 (a folate-TRPV6-peptide exatecan drug conjugate), when combined with other drugs for certain types of cancer. It targets patients with solid tumors of epithelial origin (cancers starting in the lining of organs) that have spread or cannot be surgically removed. Participants should have tried at least one standard treatment and either experienced disease progression or intolerable side effects. The trial divides participants into groups, each testing CBP-1019 with other medications like pembrolizumab (an immunotherapy drug) or FOLFOX (a chemotherapy combination) to determine the most effective combination. For those with metastatic cancer fitting these criteria who have not found success with standard treatments, this trial may be suitable. As a Phase 1 trial, the 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 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.

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

Research has shown that CBP-1019, a new cancer treatment, appears promising in early studies. These studies examined how well patients tolerated CBP-1019 when combined with other cancer drugs. Preclinical tests suggest that CBP-1019 is generally safe and well-tolerated. However, detailed information about side effects in humans remains limited.

As the trial is in its early phase, the primary focus is on ensuring the treatment's safety for humans. While some safety information is available, more will be gathered as the study progresses. If CBP-1019 receives approval for other conditions, it would provide additional evidence about its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CBP-1019 because it offers a novel approach to cancer treatment by combining with standard therapies like Pembrolizumab, FOLFOX, Bevacizumab, and Enzalutamide, potentially boosting their effectiveness. Unlike typical cancer treatments, which often target a single pathway, CBP-1019 works through a unique mechanism that might enhance the immune system's ability to fight cancer cells. This could lead to better outcomes for patients with pancreatic, colorectal, and other epithelial-origin cancers. Additionally, the possibility of using CBP-1019 in combination with existing therapies could provide a more personalized treatment strategy, making it a promising development in oncology.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research shows that CBP-1019 is a new drug targeting specific proteins often found in solid tumors. This trial studies CBP-1019 in combination with other cancer treatments across different arms. For instance, some participants will receive CBP-1019 with pembrolizumab, while others will receive it with FOLFOX and bevacizumab. Early findings suggest these combinations can effectively target tumors by delivering chemotherapy directly to cancer cells. Initial results indicate that these combinations might help shrink or slow tumor growth. Although still early, the unique targeting mechanism of CBP-1019 offers cautious hope for treating various solid tumors. ^{1 2 3 4 5}

Who Is on the Research Team?

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02233-6/fulltext

648P An open-label, MRCT phase I/II study evaluating the ... CBP-1019 is a globally first-in-class bi-specific ligand drug conjugate (Bi-XDC) that targets both FRα and TRPV6 with the payload of exatecan (DX-8951), ...

2. withpower.com withpower.com/trial/cbp-1019-combinations-for-cancer-0e683

CBP-1019 Combinations for Cancer This Phase 1 medical study run by M.D. Anderson Cancer Center is evaluating whether CBP-1019 will have tolerable side effects & efficacy for patients with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05830097

A Study of Bi-Ligand-Drug Conjugate CBP-1019 in ... The primary objective of this phase I study is to evaluate the safety and potential efficacy and to determine the recommended phase 2 dose (RP2D) of CBP-1019, a ...

4. synapse.patsnap.com synapse.patsnap.com/drug/ba40f9076bd24271b2770b321ea49fae

CBP-1019 - Drug Targets, Indications, Patents A Phase I clinical study to evaluate the safety and tolerability, pharmacokinetics and preliminary efficacy of CBP-1019 for injection in patients with advanced ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/fra-trpv6-bispecific-ligand-drug-conjugate-cbp-1019?pn=1

Clinical Trials Using FRa/TRPV6 Bispecific Ligand-drug ... Review the clinical trials studying fra/trpv6 bispecific ligand-drug conjugate cbp-1019 on this list and use the filters to refine the results by age and ...