CBP-1019 for Advanced Cancers

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Lin Shen

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing CBP-1019, a drug that targets cancer cells, in patients with advanced solid tumors who have no other treatment options. The drug works like a guided missile, finding and attacking cancer cells more precisely.

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.

What data supports the effectiveness of the drug CBP-1019 for advanced cancers?

Research on similar folate-linked drug conjugates shows they can effectively target cancer cells that overexpress folate receptors, leading to significant tumor reduction in preclinical models. This suggests that CBP-1019, which uses a similar targeting mechanism, may also be effective in treating advanced cancers. ^{1 2 3 4 5}

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

The research on similar treatments like EC131 and EC1456 shows they were effective in targeting tumors without causing significant toxicity in animal models. Additionally, exatecan mesylate, a component of CBP-1019, was studied in humans to determine safe dosage levels, although specific safety data for CBP-1019 itself is not provided. ^{3 4 6 7 8}

What makes the drug CBP-1019 unique for treating advanced cancers?

CBP-1019 is unique because it targets cancer cells that overexpress folate receptors, using a folate-peptide conjugate to deliver the drug directly to the tumor, potentially reducing side effects and increasing effectiveness compared to non-targeted therapies. ^{2 3 4 5 9}

Research Team

Lin Shen

Principal Investigator

Peking University Cancer Hospital & Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• CBP-1019 (Bi-specific Ligand Conjugated Drug)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

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

Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Antigen-independent tumor targeting by CBX-12 (alphalex™-exatecan) induces long-term antitumor immunity. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of folate receptor-targeted amphiphilic cyclodextrin nanoparticles as a novel vehicle for paclitaxel delivery in breast cancer. [2022]

9. Hungary pubmed.ncbi.nlm.nih.gov

[Application of Asn-Gly-Arg sequence based cyclic peptides for targeted tumor therapy]. [2022]