CS5001 for Advanced Cancers

Recruiting at 34 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

480 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, CS5001 (also known as ROR1 ADC), to assess its safety and effectiveness for individuals with advanced cancers, including both blood cancers and solid tumors. The trial aims to determine how well CS5001 works alone and in combination with other treatments. Suitable candidates include those with advanced cancers that have progressed after standard treatments, particularly if their tumors cannot be surgically removed. Participants should have experienced failure in previous treatment attempts and have a life expectancy of more than three months. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that CS5001 is likely to be safe for humans?

Research has shown that CS5001 is generally well tolerated by people with advanced cancers. Studies have found that even patients with many previous treatments did not experience serious side effects that would prevent them from continuing with CS5001. This indicates they could handle the treatment without major problems.

Additionally, CS5001 reportedly has low overall toxicity, meaning it doesn't cause many harmful side effects throughout the body. While this is encouraging, it's important to remember that this is the first time the drug is being tested in humans. Ongoing research will provide more information about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CS5001 is unique because it targets cancer cells directly, potentially offering a new mechanism of action compared to traditional chemotherapy and immunotherapy treatments. Unlike existing options that often come with significant side effects due to their impact on healthy cells, CS5001 aims to minimize collateral damage by honing in on the cancerous cells more precisely. Researchers are excited about this treatment because it could lead to more effective therapies with fewer side effects, improving the quality of life for patients with advanced cancers.

What evidence suggests that CS5001 might be an effective treatment for advanced cancers?

Research shows that CS5001 holds promise for treating advanced cancers. Studies have found it to be the first targeted cancer drug of its kind to show activity against both solid tumors and lymphomas. In patients with advanced lymphomas, CS5001 led to tumor shrinkage in nearly half of the cases, achieving an overall response rate of 48.4%. The treatment was well tolerated, with patients not experiencing severe side effects. These encouraging results support further research. Participants in this trial will join either a dose escalation or dose expansion arm to further evaluate the effectiveness and safety of CS5001. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

Is willing to provide tumor tissue and control blood sample.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Dose expansion Experimental Treatment 9 Interventions

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+

Published Research Related to This Trial

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]

Citations

1. cstonepharma.com cstonepharma.com/en/html/news/3763.html

CStone Presents Latest Clinical Data on CS5001 for ... CS5001 is so far the first anti-ROR1 ADC known to show clinical anti-tumor activity in both solid tumors and lymphomas.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1739/532477/Safety-and-Efficacy-in-Patients-with-Advanced

Safety and Efficacy in Patients with Advanced Lymphomas ... CS5001 was well tolerated and showed promising efficacy in patients with advanced lymphomas. Current data support continued evaluations for the ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3023

A phase 1a/b, multi-regional, first-in-human study of ... Results: As of 15 Jan 2024, 49 pts with lymphomas (n=17) and solid tumors (n=32) were treated across 8 dose levels (7 to 125 μg/kg). Median age ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124044860

Safety and Efficacy in Patients with Advanced Lymphomas ... CS5001 was well tolerated and showed promising efficacy in patients with advanced lymphomas. Current data support continued evaluations for the ...

5. prnewswire.com prnewswire.com/news-releases/encouraging-efficacy-and-safety-cstone-presents-latest-clinical-data-on-cs5001-for-advanced-lymphoma-at-the-66th-ash-annual-meeting-302325504.html

CStone Presents Latest Clinical Data on CS5001 ... Efficacy Results​​ CS5001 demonstrated encouraging anti-tumor activity in B-cell lymphomas, with an ORR of 48.4% across all dose levels; a ...

6. cstonepharma.com cstonepharma.com/en/html/news/3693.html

CStone Announces Abstract Release of CS5001 (ROR1 ... First-in-human study data show that CS5001 is well tolerated with promising anti-tumor activity at various dose levels in heavily pretreated, ...