SR-8541A + Combination Therapy for Colorectal Cancer

Recruiting at 4 trial locations

Overseen By Sunil Sharma, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stingray Therapeutics

Must not be taking: Tyrosine kinase inhibitors, Immunosuppressants

Disqualifiers: Autoimmune disease, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial explores a new treatment for colorectal cancer that has spread and cannot be surgically removed. The study tests a combination of oral SR-8541A (a potential new drug) and two other drugs administered by IV to assess their safety and effectiveness. Individuals with colorectal cancer who have undergone at least one chemotherapy treatment and have tumors not high in microsatellite instability (a specific genetic trait) might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but you cannot take certain drugs like small molecule inhibitors within 2 weeks, systemic therapy for CRC within 3 weeks, or strong CYP enzyme inhibitors or inducers. Check with the trial team about your specific medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that SR-8541A is being tested for safety in treating colorectal cancer when combined with botensilimab and balstilimab. Earlier studies found this combination generally safe, with most patients not experiencing severe side effects. Common side effects for similar treatments include fatigue, nausea, and mild skin reactions.

Since this trial is in phase 2, researchers have some basic safety information from earlier trials. This provides evidence that the treatment did not cause serious harm to previous participants. However, as with any new treatment, risks remain.

SR-8541A is not yet approved by the FDA for any condition. Therefore, it is important to carefully weigh the potential risks and benefits before joining a trial. Always consult with a healthcare provider to make the best decision for your health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for colorectal cancer?

Researchers are excited about SR-8541A for colorectal cancer because it offers a novel approach to tackling the disease, especially in cases with liver metastases. Unlike standard chemotherapy treatments that target rapidly dividing cells indiscriminately, SR-8541A is designed to specifically target cancer cells with a new mechanism of action, potentially minimizing damage to healthy cells. This precision could lead to fewer side effects and more effective tumor reduction. Additionally, SR-8541A might work synergistically with existing therapies, enhancing their effects and providing a more comprehensive treatment strategy.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that SR-8541A, when combined with other treatments, holds potential for treating colorectal cancer. In one study, about 70% of patients maintained stable disease or better, meaning their cancer did not worsen. Additionally, 17-19% of patients experienced a noticeable reduction in tumor size, with some seeing a 30% decrease in cancer burden. This trial will evaluate SR-8541A in combination therapy for colorectal cancer, offering hope for those with this condition, especially given the challenging five-year survival rate. Participants will be assigned to different treatment arms based on the presence of active liver metastases. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic colorectal cancer that's not responsive to at least one chemotherapy regimen. Participants must have a specific type of tumor (non-MSI-H/non-dMMR), measurable disease, good performance status (ECOG 0 or 1), and adequate kidney and liver function. They need to provide tumor tissue samples.

Inclusion Criteria

I have signed the consent form.

My tumor is not MSI-H/dMMR as per tests.

I can provide samples of my tumor before and possibly after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 of the study is to establish the recommended dose of SR-8541A in combination with botensilimab and balstilimab

Approximately 3 cycles of 28 days each

Treatment

Participants receive SR-8541A orally in combination with intravenous botensilimab and balstilimab

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SR-8541A

Trial Overview The study tests SR-8541A taken orally in combination with two IV drugs, botensilimab and balstilimab, focusing on their safety and effectiveness in treating colorectal cancer that has spread and does not respond well to other treatments.

How Is the Trial Designed?

Group I: MSS-CRC subject with no active liver metastases Experimental Treatment 1 Intervention

Group II: MSS-CRC subject with active liver metastases Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Stingray Therapeutics

Lead Sponsor

Trials

2

Recruited

100+

Published Research Related to This Trial

In a study involving 426 patients with metastatic colorectal cancer, the oral S-1 plus irinotecan (IRIS) regimen demonstrated non-inferior progression-free survival compared to the traditional FOLFIRI chemotherapy, with median survival times of 5.8 months for IRIS and 5.1 months for FOLFIRI.

The IRIS treatment was associated with fewer severe adverse reactions, such as neutropenia and treatment-related deaths, suggesting it may be a safer and more convenient alternative for patients requiring second-line chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Muro, K., Boku, N., Shimada, Y., et al.[2022]

In a study evaluating 21 drug combinations for treating colorectal adenocarcinoma using primary cultures, 62% of the combinations showed both effective cell death and safety, indicating potential for personalized treatment strategies.

The findings suggest that traditional treatments like 5-fluorouracil and oxaliplatin may not be effective for all patients, highlighting the importance of individualized drug testing to improve treatment outcomes and patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective efficacy and safety of first line and non front line antineoplasic agent combinations determined with individualized assays on colorectal cancer primary cultures. N Garza-Trevino, E., G Martínez Rodríguez, H., S Rodríguez González, M., et al.[2021]

The combination of S-1, a new oral derivative of 5-FU, with irinotecan (CPT-11) has been explored as a promising treatment for patients with advanced or recurrent colorectal cancer.

This article discusses the clinical use and associated toxicities of this combination therapy, highlighting its potential therapeutic value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination chemotherapy with S-1 plus CPT-11 for patients with advanced or recurrent colorectal cancer]. Tsunoda, A., Nakao, K., Kamiyama, G., et al.[2018]

In a phase II trial involving 44 patients with refractory metastatic colorectal cancer, the combination of bevacizumab, S-1, and raltitrexed demonstrated a 15.9% objective response rate and a disease control rate of 54.5%, indicating potential effectiveness in this challenging patient population.

The treatment was well tolerated, with a median progression-free survival of 110 days and overall survival of 367 days, suggesting that this combination therapy could be a viable option for patients who have not responded to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study. Chen, Y., Zhou, YW., Cheng, K., et al.[2021]

The combination treatment of 5-Fluorouracil, irinotecan, bevacizumab, and sirolimus showed promising efficacy in 12 patients with refractory advanced colorectal carcinoma, with clinical benefits observed in 8 patients and a median survival of 8 months.

While the treatment was feasible, it did lead to some significant side effects, including grade 3 neutropenia in four patients and grade 3 diarrhea and stomatitis in two patients, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal cancer: a pilot study. Ghiringhelli, F., Guiu, B., Chauffert, B., et al.[2021]

In a randomized phase II trial involving 60 patients with metastatic colorectal cancer, sequential treatment with IRIS and bevacizumab showed comparable safety to mFOLFIRI and bevacizumab, with fewer cases of grade 3 anorexia and diarrhea in the IRIS group.

Both treatment regimens demonstrated high overall response rates (62% for mFOLFIRI vs. 72% for IRIS) and similar progression-free survival times, indicating that sequential IRIS + bevacizumab is an effective option for systemic chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety verification trials of mFOLFIRI and sequential IRIS + bevacizumab as first- or second-line therapies for metastatic colorectal cancer in Japanese patients. Kato, S., Andoh, H., Gamoh, M., et al.[2022]

Chemotherapy combinations, such as fluoropyrimidine with oxaliplatin or irinotecan, are standard treatments for advanced colorectal cancer, achieving about a 50% tumor response rate and a median overall survival of 20 months.

While adding agents like bevacizumab and cetuximab can improve response rates and progression-free survival, the overall survival benefits are marginal, highlighting the need for biomarkers to better target therapies and manage costs and toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of nonsurgical therapy for colorectal cancer. Midgley, RS., Yanagisawa, Y., Kerr, DJ.[2021]

Liposomal irinotecan (Irinophore C™) demonstrated significant efficacy as a single agent in treating colorectal cancer, delaying tumor growth more effectively than the combination with 5-fluorouracil (5-FU).

The combination of IrC™ and 5-FU resulted in increased toxicity and altered pharmacokinetics of 5-FU, suggesting that while IrC™ is a promising treatment, its use with 5-FU may complicate treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of colorectal cancer using a combination of liposomal irinotecan (Irinophore C™) and 5-fluorouracil. Hare, JI., Neijzen, RW., Anantha, M., et al.[2021]

In a study of 54 patients with stage II/III resectable colorectal cancer, S-1 treatment showed a high completion rate of 77.7% over one year, indicating good patient compliance with the regimen.

The treatment was associated with minimal severe side effects, with only one patient experiencing grade 3 toxicity, suggesting that S-1 is a safe and effective option for adjuvant chemotherapy in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of S-1 adjuvant chemotherapy in patients with colorectal cancer. Ogawa, M., Watanabe, M., Kobayashi, T., et al.[2021]

5-Fluorouracil (5-FU) has been the standard treatment for colorectal cancer for 40 years, but its overall survival benefit remains limited to about 12 months, even with enhancements like leucovorin.

Capecitabine has been shown to be as effective as 5-FU and is now a first-line treatment, especially when combined with other agents like CPT-11 or oxaliplatin, which improve response rates and overall survival in patients with advanced colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of colorectal cancer metastasis: the role of chemotherapy. Xiong, HQ., Ajani, JA.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e15602

A phase 2 study of SR-8541A in combination with ... Around 70% of patients had stable disease or better, with a 17-19% objective response rate, a 30% reduction in cancer burden, and near-complete ...

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT240/761412/Abstract-CT240-A-phase-2-study-of-SR-8541A-in?searchresult=1

Abstract CT240: A phase 2 study of SR-8541A in combination ... The five-year survival rate for colorectal cancer (CRC) remains at 14% despite improvements in early detection and the development of novel ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/535736

Phase 2 Study of SR-8541A in Combination With Botensilimab ... This is an open-label, dose escalation and expansion, multi-center phase 2 study evaluating the safety and efficacy of SR-8541A administered orally in ...

4. withpower.com withpower.com/trial/sr-8541a-combination-therapy-for-colorectal-cancer-78e26

SR-8541A + Combination Therapy for Colorectal Cancer The research suggests that combination therapies involving drugs like S-1 and irinotecan (CPT-11) have shown promise in treating colorectal cancer, with ...

5. researchgate.net researchgate.net/publication/385556927_688_A_phase_1_multi-center_open-label_dose_escalation_study_to_evaluate_the_safety_and_pharmacokinetics_of_oral_SR-8541A_an_ENPP1_inhibitor_in_patients_with_advanced_solid_tumors

688 A phase 1 multi-center, open-label, dose escalation ... Conclusions: In summary, we show that SR-8541A is a potent and selective inhibitor of ENPP1 that displayed strong immune response in 3D spheroid ...

6. reporter.nih.gov reporter.nih.gov/project-details/11175164

Project Details In Aim 1, we will conduct a phase 2 trial to evaluate the safety and efficacy of SR-8541A administered orally with Agenus Botensilimab and Balstilimab for ...

7. ctv.veeva.com ctv.veeva.com/study/phase-2-study-of-sr-8541a-in-combination-with-botensilimab-and-balstilimab-in-subjects-with-refracto

Phase 2 Study of SR-8541A in Combination With ... This is an open-label, dose escalation and expansion, multi-center phase 2 study evaluating the safety and efficacy of SR-8541A administered orally in ...

8. synapse.patsnap.com synapse.patsnap.com/drug/026566c6db114b70a7aaadc9abc0f1f9

SR-8541A - Drug Targets, Indications, Patents Phase 1, Dose Escalation, Safety, Tolerability, and Pharmacokinetic Study of SR-8541A (ENPP1 Inhibitor) Administered Orally as Monotherapy or in Combination ...