CBP-1019 for Advanced Cancers

Recruiting at 4 trial locations

Overseen By Jay X Ma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Coherent Biopharma (Hefei) Co., Ltd.

Disqualifiers: Concurrent malignancy, CNS metastasis, Hepatitis B, others

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

Compensation: Varies

Number of Visits: 4

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, CBP-1019 (a folate-TRPV6-peptide exatecan drug conjugate), for individuals with advanced cancers such as lung, pancreatic, or breast cancer. The main goal is to assess the treatment's safety and potential effectiveness. Participants will receive the treatment through an IV every two weeks. The trial seeks individuals who have tried standard cancer treatments but still require assistance. It may suit those with advanced solid tumors whose disease has progressed after previous treatments. 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 therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that washout periods of prior anti-tumor treatments must be completed, which might imply stopping certain cancer treatments before starting the trial.

Is there any evidence suggesting that CBP-1019 is likely to be safe for humans?

Research has shown that CBP-1019, a new cancer treatment, is under study to determine its safety for people with advanced solid tumors. In one study, scientists examined how well patients handled CBP-1019 and found that it targets specific parts of cancer cells, linking to a chemotherapy drug. This design helps focus on cancer cells while minimizing harm to healthy cells.

Early reports from these studies indicate that participants experienced manageable side effects, such as nausea, tiredness, and low blood counts, which are common with cancer treatments. No serious problems have been reported, suggesting it is generally well-tolerated.

As this trial is in the early stages, the main goal is to find the right dose and better understand the side effects. Although data is limited, the presence of CBP-1019 in these early trials suggests some promise in terms of safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments that often rely on chemotherapy or radiation, CBP-1019 offers a new approach by targeting specific pathways involved in cancer cell growth. Researchers are excited about CBP-1019 because it is administered via intravenous infusion every two weeks, which may enhance its effectiveness in controlling advanced cancers. This treatment could potentially lead to fewer side effects and better patient outcomes compared to traditional therapies, making it a promising option for those with advanced stages of the disease.

What evidence suggests that CBP-1019 might be an effective treatment for advanced cancers?

Research has shown that CBP-1019, the investigational treatment in this trial, could be promising for advanced cancers. This drug targets two specific proteins on cancer cells, FRα and TRPV6, and carries a potent chemotherapy agent called exatecan to kill cancer cells. Early studies demonstrated that CBP-1019 effectively targets these proteins and may slow tumor growth. While detailed information from human studies is still being gathered, the mechanism of CBP-1019 suggests it could be a powerful option for treating difficult cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Lin Shen

Principal Investigator

Peking University Cancer Hospital & Institute

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors, including lung, pancreatic, colorectal, esophageal, and breast cancer. They must have tried standard treatments or be unsuitable for them. Participants need a life expectancy of at least 3 months and good performance status (able to carry out daily activities). Tumor tissue is required for testing specific receptors. Women who can bear children and men with partners who can must use approved contraception.

Inclusion Criteria

My cancer has grown after my last treatment.

My organs and bone marrow are working well.

I can provide a tumor sample for specific testing if I choose a low dose treatment.

Exclusion Criteria

I have had a fever over 38.5°C without knowing why.

I have an active Hepatitis B infection with specific virus levels.

I haven't had any cancer other than early-stage skin or superficial bladder cancer in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase Ia)

Participants receive CBP-1019 IV infusion every 2 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)

28 days

Every 2 weeks

Treatment (Phase Ib/II)

Participants receive RP2D CBP-1019 IV infusion every two weeks until disease progression or intolerability

Up to 12 months

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CBP-1019

Trial Overview The trial tests CBP-1019's safety and effectiveness in treating various advanced cancers. It aims to find the best dose for phase II trials. Patients will receive CBP-1019 to see how well it works against their cancer and what side effects it may cause.

How Is the Trial Designed?

Group I: Ia stage - CBP-1019 Dose escalation/ Ib、II stage - CBP-1019 monotherapy Experimental Treatment 1 Intervention

Ia:Patients will receive CBP-1019 IV infusion every 2 weeks until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue. Ib:Patients will receive CBP-1019 RP2D IV infusion every two weeks until disease Patients will receive CBP-1019 RP2D IV infusion every two weeks until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue.

Who Is Running the Clinical Trial?

Coherent Biopharma (Hefei) Co., Ltd.

Lead Sponsor

Trials

1

Recruited

260+

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]

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]

The study demonstrated that two peptide-daunomycin conjugates effectively inhibited tumor growth in both CD13+ Kaposi's sarcoma and CD13- HT-29 colon adenocarcinoma models in SCID mice, indicating their potential as targeted cancer therapies.

Conjugate 1 showed greater potency against CD13+ tumors due to its stable structure and CD13 receptor recognition, while conjugate 2 was more effective against CD13- tumors, highlighting the importance of integrin binding, and both conjugates exhibited lower toxicity compared to free daunomycin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of Asn-Gly-Arg sequence based cyclic peptides for targeted tumor therapy]. Mező, GM., Tripodi Angelo Pierluigi, ATAP., Ranđelovič, IR., et al.[2022]

The maximum-tolerated dose (MTD) of Exatecan mesylate (DX-8951f) for patients with advanced solid tumors was determined to be 2.4 mg/m², with granulocytopenia identified as the dose-limiting toxicity (DLT) for minimally pretreated patients.

While no complete or partial responses were observed, four patients achieved stable disease, indicating some level of efficacy; the pharmacokinetic profile of DX-8951f was linear, suggesting predictable behavior at the administered doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog. Royce, ME., Hoff, PM., Dumas, P., et al.[2017]

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]

Folate-conjugated cyclodextrin nanoparticles (FCD-1) effectively target folate receptor-positive breast cancer cells, showing lower toxicity compared to traditional delivery methods like Cremophor® while maintaining similar anticancer efficacy with paclitaxel.

In animal studies, FCD-1 nanoparticles not only localized effectively at tumor sites but also significantly improved survival rates and reduced tumor burden, indicating their potential as a safer and more efficient drug delivery system for treating metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of folate receptor-targeted amphiphilic cyclodextrin nanoparticles as a novel vehicle for paclitaxel delivery in breast cancer. Erdoğar, N., Esendağlı, G., Nielsen, TT., et al.[2022]

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]

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. 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 ...

3. 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 ...

4. withpower.com withpower.com/trial/phase-2-breast-neoplasms-2-2023-6e9a7

CBP-1019 for Advanced Cancers This trial is testing CBP-1019, a drug that targets cancer cells, in patients with advanced solid tumors who have no other treatment options.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06576037

Phase Ib Study of CBP-1019 in Combination With FOLFOX ... 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 ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07312

CBP-1019 with FOLFOX with or without Bevacizumab ... CBP-1019 is a kind of drug called a bispecific ligand-drug conjugate. It targets receptors on tumor cells and is linked to a chemotherapy drug that may attack ...