CTX131 for Resistant or Recurrent Cancer

No longer recruiting at 7 trial locations

Overseen By Central Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: CRISPR Therapeutics AG

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS, Cardiac, Pulmonary, Infections, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CTX131 to determine its safety and effectiveness for people with certain cancers that have returned or do not respond to other treatments. The cancers under study include those affecting the kidneys, cervix, pancreas, esophagus, and the lining of the lungs. Participants will receive CTX131 through an IV after undergoing special chemotherapy to prepare their bodies. Individuals with one of these cancers that cannot be removed or has spread, and who are otherwise in fairly good health, might be suitable for the trial. 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 treatment.

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, if you are on steroids or other immunosuppressive therapy for an autoimmune disease, you may not be eligible to participate.

Is there any evidence suggesting that CTX131 is likely to be safe for humans?

Research shows that specific safety information for CTX131 in humans is not yet available. This early-phase study tests CTX131 to determine its safety for people with certain types of cancer. Early studies typically begin with small groups to ensure safety before involving more participants. CTX131 is a type of CAR T cell therapy, which uses a patient's own immune cells to combat cancer. Although these therapies have shown promise in treating cancer, side effects can occur. Prospective participants should be aware that the treatment remains in the early testing stages, and researchers are closely monitoring for any side effects to ensure participant safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CTX131 is unique because it uses a type of immune cell therapy known as CAR-T cells, specifically engineered to target and destroy resistant or recurrent cancer cells. Unlike traditional chemotherapy or radiation, which can affect both healthy and cancerous cells, CTX131 is designed to precisely attack cancer cells, potentially reducing side effects. Researchers are excited about this treatment because it represents a targeted approach, offering hope for patients whose cancers have not responded to existing therapies. Additionally, the administration of CTX131 via IV infusion following lymphodepleting chemotherapy could enhance its effectiveness by creating an optimal environment for the CAR-T cells to thrive.

What evidence suggests that CTX131 might be an effective treatment for resistant or recurrent cancer?

Research has shown that CTX131, the investigational treatment in this trial, targets cancer stem cells, which often cause cancer to resist regular treatments. By focusing on these stubborn cells, CTX131 aims to improve treatment results for people with solid tumors that have returned or resisted other therapies. Early findings suggest that CTX131 may boost the immune system and reduce treatment fatigue in lab tests. This has led to hope about its potential effectiveness for cancers with a specific marker called CD70. Overall, CTX131 is being studied as a promising new option for treating difficult cancers. ^{1 2 4 6 7}

Who Is on the Research Team?

Alissa Keegan, MD, PhD

Principal Investigator

CRISPR Therapeutics

Are You a Good Fit for This Trial?

Adults over 18 with certain advanced cancers (like kidney, cervical, pancreatic cancer, and mesothelioma) that have come back or didn't respond to treatment. They must be in good physical condition and agree to use birth control for a year after getting the study drug.

Inclusion Criteria

I agree to use birth control from enrollment until at least 12 months after my treatment.

My cancer is advanced and cannot be removed by surgery.

My kidney, liver, heart, and lung functions are all within normal ranges.

Exclusion Criteria

I have a history of specific brain, heart, or lung conditions.

I am not pregnant or breastfeeding.

I have an immune system disorder or autoimmune disease and need steroids or other treatments to manage it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CTX131 infusion

1-2 weeks

Treatment

CTX131 is administered by IV infusion following lymphodepleting chemotherapy

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

What Are the Treatments Tested in This Trial?

Interventions

• CTX131

Trial Overview The trial is testing CTX131's safety and effectiveness on patients with specific solid tumors that are either untreatable or have returned after treatment. It's an early-phase study where everyone gets the same experimental therapy.

How Is the Trial Designed?

Group I: CTX131 Experimental Treatment 1 Intervention

Administered by IV infusion following lymphodepleting chemotherapy.

Who Is Running the Clinical Trial?

CRISPR Therapeutics AG

Lead Sponsor

Trials

9

Recruited

640+

Published Research Related to This Trial

In ovarian cancer cell lines, specifically OVCAR-3, -4, and -5, the combination of CD133 and CXCR4 markers identified a population with strong cancer stem cell characteristics, which was linked to enhanced tumor formation in animal models.

The CD133(+)CXCR4(+) cells showed resistance to cisplatin and overexpressed the ABCG2 drug transporter, indicating that targeting this specific cell population could be a promising strategy for overcoming chemotherapy resistance in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a distinct population of CD133(+)CXCR4(+) cancer stem cells in ovarian cancer. Cioffi, M., D'Alterio, C., Camerlingo, R., et al.[2021]

In a study of 105 patients with locally advanced rectal cancer, CD133 expression significantly increased after neoadjuvant chemoradiotherapy (nCRT), indicating that nCRT may enhance CD133 levels in rectal cancer tissues.

Patients with CD133-positive tumors showed a lower response to nCRT, suggesting that targeting CD133 could potentially improve the effectiveness of nCRT in treating rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression of CD133 in rectal cancer tissues and its relationship with neoadjuvant chemoradiotherapy]. Li, D., Wu, H., Feng, R., et al.[2020]

Anti-CD133 CAR-T cells effectively target and kill cisplatin-resistant gastric cancer stem cells, showing increased activation and cytokine production after treatment, which suggests a strong immune response.

The combination of cisplatin and anti-CD133 CAR-T therapy significantly reduces tumor growth and the presence of cancer stem cells in multiple xenograft models, indicating a promising strategy for improving treatment outcomes in aggressive gastric cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti-CD133 CAR-T combination therapy. Han, Y., Sun, B., Cai, H., et al.[2021]

In a study of 32 rectal cancer patients, higher expression of CD133 was linked to greater sensitivity to preoperative radiotherapy, suggesting it could be a useful biomarker for predicting treatment response.

The research found that CD133 expression and the differentiation of rectal cancer are independent predictive factors for how well patients respond to radiotherapy, highlighting the potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Association of CD133 expression and sensitivity of rectal cancer to preoperative radiotherapy]. Qiu, JM., Yang, GG., Lu, XJ., et al.[2018]

Low-dose metronomic chemotherapy using cyclophosphamide and methotrexate showed a 15.7% rate of prolonged clinical benefit in patients with metastatic breast cancer, with a median follow-up of 23 months.

Among the 153 patients studied, some achieved significant responses, including complete remission lasting up to 42 months after stopping treatment, highlighting the potential of this approach as an effective therapy for metastatic breast carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer. Orlando, L., Cardillo, A., Rocca, A., et al.[2022]

In a study of 28 patients with advanced castrate-resistant prostate cancer (CRPC), second-line chemotherapy using capecitabine, cyclophosphamide, thalidomide, and prednisone showed promising efficacy, with 35.7% of patients experiencing a significant decrease in prostate-specific antigen levels.

The treatment demonstrated an excellent safety profile, as no patients experienced severe (grade 3-4) toxicities, while the median overall survival was 19.5 months, indicating that this combination therapy is both effective and safe for advanced CRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients. Meng, LJ., Wang, J., Fan, WF., et al.[2021]

Radioimmunotherapy (RIT) using the 131I-AC133.1 monoclonal antibody effectively targeted CD133(+) colonic cancer stem cells in tumor-bearing mice, leading to significantly longer survival times and slower tumor growth compared to control groups.

The treatment resulted in lower levels of cancer stem-like biomarkers and higher levels of E-cadherin, indicating a reduction in cancer stem cell characteristics and promoting tumor necrosis, which suggests that RIT can effectively inhibit tumor development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy for CD133(+) colonic cancer stem cells inhibits tumor development in nude mice. Weng, D., Jin, X., Qin, S., et al.[2018]

In a study of 49 colon cancer patients, co-expression of CXCR4 and CD133 was found to be significantly associated with poorer prognosis, as indicated by a 3-year survival rate of only 27.3% for those with co-expression compared to 76.3% for others.

The expression of CXCR4 and CD133 was linked to advanced TNM staging and lymphatic metastasis, suggesting that these markers could help identify patients at higher risk for aggressive disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of CXCR4 and CD133 co-expression on the prognosis of patients with stage II~III colon cancer. Li, XF., Guo, XG., Yang, YY., et al.[2019]

C-1311, an anticancer agent, was tested in a phase 1 trial with 22 patients, showing a recommended dose of 480 mg/m² that provided a predictable safety profile and good tolerability, despite all patients experiencing treatment-related adverse events.

The most common side effects included neutropenia and nausea, with some severe cases of neutropenia, indicating that while C-1311 has potential anti-tumor activity, careful monitoring of blood-related side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours. Isambert, N., Campone, M., Bourbouloux, E., et al.[2017]

In a phase II study involving 68 women with metastatic breast cancer, the combination of oral metronomic cyclophosphamide and capecitabine showed a median time to progression of 5.2 months and a median overall survival of 16.9 months, indicating its efficacy as a treatment option.

The treatment was well tolerated, with only anorexia being a significant grade 3/4 adverse event in 7.5% of patients, suggesting a favorable safety profile for this all-oral regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An all-oral combination of metronomic cyclophosphamide plus capecitabine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: a phase II study. Wang, Z., Lu, J., Leaw, S., et al.[2022]

In a study of 58 patients with metastatic castration-resistant prostate cancer (CRPC) who progressed after docetaxel, 25% showed a significant PSA response (≥50% reduction), indicating that low-dose oral cyclophosphamide and methotrexate can be effective in this population.

The treatment was generally well-tolerated, with manageable toxicity; however, some patients experienced grade 3 leukopenia and thrombocytopenia, suggesting that while the regimen is feasible, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel. Gebbia, V., Serretta, V., Borsellino, N., et al.[2018]

In a study of 74 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel, certain circulating tumor cell (CTC) gene expressions, such as AR-V7 and EPCAM, were significantly associated with overall survival, indicating their potential as prognostic biomarkers.

Patients treated with a lower dose of cabazitaxel (20 mg/sqm) who were AR-V7 positive had a notably shorter median overall survival (6.6 months) compared to AR-V7 negative patients (14 months), suggesting that AR-V7 positivity may indicate poorer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel. Gurioli, G., Conteduca, V., Brighi, N., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-carcinoma-2-2023-42b4f

CTX131 for Resistant or Recurrent Cancer CTX131 is unique because it targets cancer stem cells, which are often responsible for resistance to traditional treatments. This approach may improve outcomes ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05795595

A Safety and Efficacy Study Evaluating CTX131 in Adult ... This is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX131™ in subjects with relapsed or refractory solid tumors. Detailed ...

3. ir.crisprtx.com ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-announces-updates-immuno-oncology-pipeline

Press Release CTX131 is being investigated in a clinical trial designed to assess the safety and efficacy of the product candidate in adult patients with ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT05795595

A Safety and Efficacy Study Evaluating CTX131 in Adult ... The trial's findings provide a proof of concept, meriting further exploration of CD70-targeted CAR T cell therapy in ccRCC and other CD70-positive cancers.

5. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/ND02/727041/Abstract-ND02-CTX112-and-CTX131-Next-generation

Abstract ND02: CTX112 and CTX131: Next-generation ... CTX112 and CTX131 demonstrated increased expansion, resistance to exhaustion, and elevated effector cytokine release when tested using in vitro ...

6. ir.crisprtx.com ir.crisprtx.com/static-files/ce2efeb9-3319-4504-8430-13058b305455

CTX112 and CTX131 CTX131. NCT05795595. A Safety and Efficacy Study Evaluating CTX131 in Adult Subjects. With Relapsed or Refractory Solid Tumors. 14. Page 16. Preclinical Data of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10623081/

Genome Editing in Engineered T Cells for Cancer ... We review emerging applications of genome editing approaches designed to (1) overcome resistance to therapy, including cancer immune evasion mechanisms.