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

Trial Summary

What is the purpose of this trial?

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 combination with intravenous botensilimab and balstilimab in subjects with MSS-CRC with and without active liver metastases.

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.

What data supports the effectiveness of the drug SR-8541A in 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 improved response rates and survival outcomes. Additionally, combinations of 5-FU with other agents like oxaliplatin or irinotecan are standard treatments, indicating that similar combination approaches may be effective. ^{1 2 3 4 5}

What safety data exists for SR-8541A and its combinations in humans?

The combination of bevacizumab with S-1 and raltitrexed showed acceptable safety in patients with metastatic colorectal cancer. Additionally, a study on S-1 alone for colorectal cancer patients reported on its safety and compliance over a year of treatment. ^{3 6 7 8 9}

What makes the drug SR-8541A unique for colorectal cancer treatment?

SR-8541A is unique because it is used in combination with other therapies, potentially including S-1 and irinotecan (CPT-11), which have shown promise in improving treatment outcomes for colorectal cancer. This combination may offer a novel approach compared to traditional 5-FU-based therapies, which have been the standard for many years. ^{1 2 5 6 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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 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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Combination chemotherapy with S-1 plus CPT-11 for patients with advanced or recurrent colorectal cancer]. [2018]

2. Switzerland 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. [2022]

3. Cyprus 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Evolution of nonsurgical therapy for colorectal cancer. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of colorectal cancer metastasis: the role of chemotherapy. [2019]

6. England 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). [2022]

7. England 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. [2021]

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

Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal cancer: a pilot study. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

Feasibility study of S-1 adjuvant chemotherapy in patients with colorectal cancer. [2021]

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

Treatment of colorectal cancer using a combination of liposomal irinotecan (Irinophore C™) and 5-fluorouracil. [2021]