CPO301 for Cancer

Recruiting at 12 trial locations

Overseen By Audrey Li

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Conjupro Biotherapeutics, Inc.

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

Disqualifiers: CNS metastasis, Carcinomatous meningitis, others

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

Compensation: Varies

Number of Visits: 10

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, CPO301, to determine its safety and tolerability in individuals with advanced or hard-to-treat solid tumors, such as certain lung cancers. Initially, the trial will explore different doses to identify the optimal one, then assess the drug's effectiveness at that dose, particularly in lung cancer patients with specific gene changes. Participants will have solid tumors that have worsened or not responded to previous treatments. Those with such conditions who are not responding to standard treatments might be suitable for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that CPO301 is likely to be safe for humans?

Research shows that CPO301 remains in the early stages of safety testing. Scientists are beginning to observe how the drug affects people. Earlier studies with animals found that CPO301 slowed the growth of tumors with certain mutations. However, results in animals do not always predict human reactions.

Since this trial is in the first phase, it focuses on determining if CPO301 is safe and identifying potential side effects. This phase typically involves a small number of participants and helps establish a safe dose for future studies. Although specific safety data for humans is not yet available, this phase is designed to monitor closely for any negative effects. Participants receive the drug every three weeks, with doses gradually increasing to find a safe level. The goal is to ensure any side effects remain manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CPO301 because it offers a novel approach to cancer treatment by potentially targeting cancer cells more precisely. Unlike standard chemotherapy, which can affect both healthy and cancerous cells, CPO301 is designed to escalate doses gradually, allowing for more targeted and potentially less harmful treatment. This precision in dosage could minimize side effects and improve patient outcomes, making it a promising option for those battling cancer.

What evidence suggests that CPO301 might be an effective treatment for cancer?

Research has shown that CPO301, a type of targeted cancer treatment, yields promising results for certain cancers. In earlier studies, CPO301 effectively targeted tumors, particularly in non-small cell lung cancer (NSCLC) with specific genetic changes. These changes, known as Exon19Del, T790M, and C797S mutations, often resist regular therapies. The drug specifically attacks and destroys cancer cells in these cases. This trial will evaluate CPO301 in two parts: Part A involves dose escalation to determine the recommended phase 2 dose, and Part B involves dose expansion at that determined dose. This suggests that CPO301 could benefit patients with advanced or spreading solid tumors, especially those with these challenging mutations. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• CPO301

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05948865

NCT05948865 | A Phase 1 Study of CPO301 in Adult ... The goal of this clinical trial is to test CPO301, a type of drug called an antibody drug conjugate in adult patients with advanced or metastatic solid ...

2. adcreview.com adcreview.com/drugmap/cpo301/

CPO301 CPO301 showed a strong anti-tumor effect especially in the PDX model of humanized NSCLC containing EGFR triple mutations (Exon19Del, T790M and C797S) that were ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01830

Mutant Non–Small-Cell Lung Cancer The primary end point, confirmed objective response rate (ORR), was 29.8%, with a median duration of response and PFS of 6.4 and 5.5 months, ...

4. withpower.com withpower.com/trial/phase-1-lung-neoplasms-5-2023-df327

CPO301 for Cancer · Recruiting Participants for Phase ... 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.

5. pryzm.ozmosi.com pryzm.ozmosi.com/product/30757

CPO-301 Drug Profile A first-in-class antibody drug conjugate developed by CSPC, has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the.

6. onco-this-week.com onco-this-week.com/cpo301-granted-the-fast-track-designation-by-u-s-fda-for-the-treatment-of-adult-patients-with-nsclc/

CPO301 granted the fast track designation by U.S. FDA for ... Updated Elironrasib Safety & Efficacy Data in Patients with KRAS G12C NSCLC Following Treatment with a KRAS(OFF) G12C Inhibitor Presented.