CPO301 for Cancer

Recruiting at 12 trial locations

Overseen By Audrey Li

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Conjupro Biotherapeutics, Inc.

Must not be taking: Chemotherapy, Radiotherapy, Immunotherapy, others

Disqualifiers: CNS metastasis, Carcinomatous meningitis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests CPO301, a drug that targets and kills cancer cells, in adults with advanced or metastatic solid tumors who have limited treatment options. The drug uses an antibody to find cancer cells and deliver chemotherapy directly to them.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received other investigational drugs or certain anti-tumor treatments within 2 to 4 weeks before starting the trial drug.

How does the drug CPO301 differ from other cancer treatments?

CPO301 is unique because it may involve a combination approach that enhances the effectiveness of existing cancer drugs like CPT-11 by targeting specific cellular mechanisms, such as inhibiting PLK1, which can improve the drug's ability to kill cancer cells, even those resistant to standard treatments. ^{1 2 3 4 5}

Eligibility Criteria

Adults with advanced or metastatic solid tumors, including lung cancer, who have progressed after prior treatments or can't tolerate them. Participants must be over 18, have a life expectancy of more than 12 weeks and at least one measurable tumor. Those with specific EGFR mutations in their lung cancer are also eligible.

Inclusion Criteria

I have at least one tumor that can be measured on a scan.

I have a solid tumor such as lung, breast, colorectal (without KRAS mutation), or head & neck cancer.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

My side effects from cancer treatment are mild, except for hair loss.

It's been over 4 weeks since my last major cancer treatment and over 2 weeks since any minor treatment.

I have not had major surgery in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation (Part A)

Participants receive escalating doses of CPO301 to determine the maximum tolerated dose (MTD) or recommended dose

21 days per cycle, multiple cycles

Every 3 weeks (in-person)

Dose Expansion (Part B)

Participants receive CPO301 at the recommended phase 2 dose (RP2D) determined in Part A

21 days per cycle, multiple cycles

Every 3 weeks (in-person)

Follow-up

Participants are monitored for progression every 3 months for up to 2 years

Up to 2 years

Every 3 months (in-person)

Treatment Details

Interventions

• CPO301 (Monoclonal Antibodies)

Trial Overview CPO301 is being tested for safety and effectiveness in two parts: first to find the right dose (Part A) and then to test it on non-small cell lung cancer patients with EGFR mutations and other cancers (Part B). It's given by IV every three weeks.

Participant Groups

Group I: Part B, Dose Expansion Experimental Treatment 1 Intervention

Participants receive CPO301 at the recommended phase 2 dose (RP2D) determined in Part A, administered by IVI every 3 weeks (Q3W), with 21 days as a treatment cycle.

Group II: Part A, Dose Escalation Experimental Treatment 1 Intervention

Participants receive escalating doses of CPO301 of 0.6 mg/kg, 1.8mg/kg, 3.6 mg/kg, 4.8 mg/kg, 6.4 mg/kg and 8 mg/kg administered by IVI every 3 weeks (Q3W), with 21 days as a treatment cycle.

Who Is Running the Clinical Trial?

Conjupro Biotherapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

270+

Findings from Research

Inhibition of the mitotic kinase PLK1 enhances the effectiveness of the chemotherapy drug CPT11 (SN38) in both sensitive and resistant squamous cell carcinoma (SCC) and pediatric sarcoma cell lines, leading to increased apoptosis.

Combining CPT11 with the PLK1 inhibitor BI2536 resulted in improved antitumor effects in SCC xenograft models in mice, showing a high rate of complete responses and cures, suggesting that targeting PLK1 could be a promising strategy to overcome drug resistance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PLK1 is a critical determinant of tumor cell sensitivity to CPT11 and its inhibition enhances the drug antitumor efficacy in squamous cell carcinoma models sensitive and resistant to camptothecins. Zuco, V., De Cesare, M., Zaffaroni, N., et al.[2023]

SN38, the active metabolite of CPT-11, rapidly activates the epidermal growth factor receptor (EGFR) in gastric cancer cells, leading to increased production of growth factors and inflammatory cytokines, which may promote tumor growth.

Blocking EGFR activation with gefitinib can prevent the effects induced by SN38, suggesting that combining CPT-11 with gefitinib could enhance treatment efficacy for gastric cancers by targeting EGF signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells. Kishida, O., Miyazaki, Y., Murayama, Y., et al.[2018]

In a Phase II study involving 22 adults with recurrent anaplastic oligodendroglioma (AO) who were resistant to temozolomide, CPT-11 showed modest efficacy with a 6-month progression-free survival (PFS) rate of 33%.

CPT-11 was associated with manageable toxicity, including diarrhea and neutropenia, indicating it could be a viable treatment option for patients with limited alternatives after failing standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPT-11 for recurrent temozolomide-refractory 1p19q co-deleted anaplastic oligodendroglioma. Chamberlain, MC., Glantz, MJ.[2021]

EZN-2208, a pegylated SN38-drug conjugate, shows significantly greater and longer-lasting down-regulation of HIF-1α compared to CPT-11, leading to enhanced tumor growth inhibition in various cancer models.

The superior anti-angiogenic activity of EZN-2208, demonstrated by its ability to reduce microvessel density and inhibit angiogenesis, contributes to its enhanced antitumor efficacy, with ongoing clinical trials evaluating its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent and sustained inhibition of HIF-1α and downstream genes by a polyethyleneglycol-SN38 conjugate, EZN-2208, results in anti-angiogenic effects. Sapra, P., Kraft, P., Pastorino, F., et al.[2021]

CPT-11, a prodrug used in colorectal cancer treatment, is activated by carboxylesterases to produce the active metabolite SN-38, which inhibits topoisomerase I; this study evaluated the activities of these enzymes in 53 colorectal tumors and adjacent normal tissues.

The study found that carboxylesterase activity in primary tumors was only slightly lower than in normal liver tissue, suggesting that tumors may effectively convert CPT-11 to its active form, and there was a significant variability in topoisomerase I levels, which correlated inversely with disease stage, indicating potential for personalized chemotherapy responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPT-11 converting carboxylesterase and topoisomerase activities in tumour and normal colon and liver tissues. Guichard, S., Terret, C., Hennebelle, I., et al.[2018]

References

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

PLK1 is a critical determinant of tumor cell sensitivity to CPT11 and its inhibition enhances the drug antitumor efficacy in squamous cell carcinoma models sensitive and resistant to camptothecins. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells. [2018]

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

CPT-11 for recurrent temozolomide-refractory 1p19q co-deleted anaplastic oligodendroglioma. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Potent and sustained inhibition of HIF-1α and downstream genes by a polyethyleneglycol-SN38 conjugate, EZN-2208, results in anti-angiogenic effects. [2021]

5. England pubmed.ncbi.nlm.nih.gov

CPT-11 converting carboxylesterase and topoisomerase activities in tumour and normal colon and liver tissues. [2018]