CS5001 for Advanced Cancers

Recruiting at 28 trial locations

Overseen By Crystal Wang

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: CStone Pharmaceuticals

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

Disqualifiers: CNS metastasis, Active infections, Cardiovascular disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

156 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called CS5001 to see if it is safe and effective for patients with advanced blood-related and solid cancers. The drug aims to attack and stop the growth of cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 21 days before starting the study drug.

What makes the drug CS5001 unique for treating advanced cancers?

CS5001 is an antibody-drug conjugate (ADC) that targets the ROR1 protein, which is often found on cancer cells but not on most normal cells. This allows CS5001 to deliver its toxic payload directly to cancer cells, potentially reducing side effects compared to traditional chemotherapy. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with advanced solid tumors or lymphomas that have worsened after treatment. They must have at least one measurable tumor, a life expectancy over 3 months, good performance status and organ function, agree to provide tissue samples and use contraception. Not eligible if they've had certain other cancers, active infections or HIV/AIDS, recent heart issues or treatments, are pregnant/breastfeeding, or have untreated brain metastases.

Inclusion Criteria

My solid tumor is advanced, cannot be surgically removed, and has worsened after treatment.

I have at least one tumor that can be measured according to specific criteria.

I am of childbearing age and have a negative pregnancy test.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have not had serious heart problems in the last 6 months.

I have an immune system disorder or need steroids for another health issue.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive CS5001 to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

About 6 months

Injections once every three weeks

Dose Expansion

Participants receive CS5001 at the RP2D to further evaluate safety and efficacy

About 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CS5001

Trial Overview The study tests CS5001 in patients with advanced tumors/lymphomas who've seen their disease progress after prior therapies. It's the first time this drug is being tried in humans (FIH), aiming to assess its safety and early effectiveness.

Participant Groups

Group I: Dose expansion Experimental Treatment 1 Intervention

Group II: Dose escalation Experimental Treatment 1 Intervention

CS5001 is already approved in United States, China for the following indications:

Approved in United States as CS5001 for:

• Advanced lymphomas
• Solid tumors

Approved in China as CS5001 for:

• Advanced lymphomas
• Solid tumors

Who Is Running the Clinical Trial?

CStone Pharmaceuticals

Lead Sponsor

Trials

28

Recruited

4,100+

Findings from Research

ROR1 is significantly overexpressed in colorectal carcinoma (CRC) tissues compared to adjacent non-tumor tissues, and its expression correlates with larger tumor size and advanced disease stages (III and IV).

Down-regulating ROR1 in CRC cells led to reduced cell proliferation and increased apoptosis, suggesting that targeting ROR1 could be a potential therapeutic strategy in treating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Down-regulation of receptor-tyrosine-kinase-like orphan receptor 1 suppresses cell growth and enhances apoptosis in human colorectal carcinoma]. Ma, W., He, X., Zhang, H., et al.[2016]

Antibody-drug conjugates (ADCs) are innovative cancer treatments that combine monoclonal antibodies with toxic drugs, allowing for targeted delivery to cancer cells, which results in fewer side effects compared to traditional chemotherapy.

Currently, there are 10 FDA-approved ADCs, and around 80 more are being tested in clinical trials, with a notable focus on ADCs targeting the ROR1 protein, indicating its potential as a promising target for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on the development of antibody-drug conjugates targeting ROR1 for hematological and solid cancers. Peng, H.[2021]

ROR1 is overexpressed in basal-like breast cancer (BLBC) and is linked to poor patient prognosis, making it a promising target for therapy.

An anti-ROR1 immunotoxin effectively kills ROR1+ cancer cells and slows tumor growth in models, while ROR1 also stabilizes FGFR, promoting cancer cell invasion, indicating its role in cancer progression and potential as a therapeutic target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer. Pandey, G., Borcherding, N., Kolb, R., et al.[2023]

The study developed a new monoclonal antibody (6D4) that effectively detects cell surface ROR1 in various cancers, including ovarian, triple-negative breast, and lung adenocarcinomas, indicating its potential as a target for cancer therapy.

However, ROR1 is also expressed in several normal tissues, raising concerns about potential on-target, off-tumor toxicities when using ROR1-targeted therapies, which necessitates careful monitoring for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Balakrishnan, A., Goodpaster, T., Randolph-Habecker, J., et al.[2021]

Chemotherapy treatment in breast cancer cells increases the expression of ROR1, a receptor associated with cancer stem cell features, which may contribute to tumor aggressiveness and resistance to treatment.

Using the anti-ROR1 monoclonal antibody cirmtuzumab in combination with paclitaxel significantly improved treatment outcomes in mouse models of breast cancer, suggesting that targeting ROR1 could enhance the effectiveness of chemotherapy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody. Zhang, S., Zhang, H., Ghia, EM., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Down-regulation of receptor-tyrosine-kinase-like orphan receptor 1 suppresses cell growth and enhances apoptosis in human colorectal carcinoma]. [2016]

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

Perspectives on the development of antibody-drug conjugates targeting ROR1 for hematological and solid cancers. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer. [2023]

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

Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. [2021]

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

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody. [2021]