CYAD-101 + Chemotherapy for Colorectal Cancer

(alloSHRINK Trial)

Recruiting at 3 trial locations

Overseen By Celyad Oncology Medical Monitor, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celyad Oncology SA

Must not be taking: Growth factors

Disqualifiers: CNS involvement, Stem cell transplant, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

49 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the alloSHRINK study is to assess the safety, cell kinetics and clinical activity of CYAD-101 in patients with unresectable metastatic colorectal cancer administered after standard chemotherapy

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that any non-cancer investigational agents should be stopped 3 weeks before starting the trial, and certain growth factors should be stopped 7 days before. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug CYAD-101 + Chemotherapy for Colorectal Cancer?

The combination of chemotherapy drugs like fluorouracil, folinic acid, and irinotecan (known as FOLFIRI) has been shown to increase survival time in colorectal cancer patients by about 3 months compared to some other treatments. Additionally, adding oxaliplatin to this combination (FOLFOX) has been found to improve tumor response and progression-free survival, although it may cause more side effects. ^{1 2 3 4 5}

Is the combination of CYAD-101 and chemotherapy safe for humans?

The chemotherapy regimens FOLFOX and FOLFIRI, which include drugs like irinotecan, folinic acid, and fluorouracil, have been studied for safety in treating colorectal cancer. These treatments can increase survival but may cause side effects like severe diarrhea, neuropathies (nerve damage), and neutropenia (low white blood cell count). ^{1 4 6 7 8}

What makes the CYAD-101 + Chemotherapy treatment unique for colorectal cancer?

The CYAD-101 + Chemotherapy treatment is unique because it combines a novel cell therapy (CYAD-101) with standard chemotherapy regimens (FOLFIRI or FOLFOX), potentially enhancing the immune system's ability to target cancer cells, which is different from traditional chemotherapy alone. ^{1 3 6 9 10}

Eligibility Criteria

This trial is for adults with metastatic colorectal cancer that can't be surgically removed and has worsened after treatment. They should have had FOLFIRI chemotherapy within the last 3 months, be in good physical condition (ECOG status 0 or 1), and have organs functioning well. People with brain cancer spread, recent non-cancer experimental treatments, prior cell therapies, or certain growth factor drugs can't join.

Inclusion Criteria

My cancer is a type of colon or rectal cancer that has spread.

My cancer in the colon or rectum cannot be removed by surgery and has spread.

My cancer has returned or worsened after treatment for its spread.

Exclusion Criteria

Any non-cancer-directed investigational agent within 3 weeks before the planned day for the first CYAD-101 administration

My cancer has spread to my brain or spinal cord.

I haven't taken Filgrastim or similar drugs in the last 7 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive standard FOLFOX or FOLFIRI chemotherapy

8-12 weeks

Treatment

Participants receive multiple doses of CYAD-101 after chemotherapy

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CYAD-101
• FOLFIRI
• FOLFOX

Trial Overview The alloSHRINK study tests CYAD-101 cells given after standard chemo (FOLFOX or FOLFIRI) to see how safe they are and how they affect colorectal cancer. It measures if these special immune cells can help control the disease when combined with usual treatments.

Participant Groups

Group I: CYAD-101 with FOLFOX Experimental Treatment 2 Interventions

Infusion after standard FOLFOX chemotherapy

Group II: CYAD-101 with FOLFIRI Experimental Treatment 2 Interventions

Infusion after standard FOLFIRI chemotherapy

Who Is Running the Clinical Trial?

Celyad Oncology SA

Lead Sponsor

Trials

13

Recruited

1,300+

Findings from Research

The combination of fluorouracil and folinic acid (LV-5FU2 protocol) is the preferred first-line treatment for metastatic colorectal cancer, showing better efficacy and tolerability compared to other protocols like the Mayo Clinic protocol.

Adding oxaliplatin (FOLFOX protocol) or irinotecan (FOLFIRI protocol) to the fluorouracil + folinic acid regimen improves tumor response rates and survival times, although these combinations also increase the risk of severe side effects such as neuropathy and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer: fluorouracil plus folinic acid and irinotecan or oxaliplatin. [2013]

Colorectal cancer (CRC) is a major cause of cancer-related deaths, with only about 60% of patients surviving five years post-diagnosis, highlighting the need for effective treatments.

Adjuvant chemotherapy significantly benefits stage III CRC patients, and new agents like irinotecan improve survival rates in metastatic cases, suggesting advancements in treatment options and the potential for targeted screening based on familial risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidemiology, treatment and chemoprevention in colorectal cancer. Rougier, P., Mitry, E.[2020]

In patients with inoperable or metastatic colorectal cancer, initial treatment with single-agent fluorouracil (or capecitabine) is recommended over combination therapies when the disease is unlikely to become operable, as it does not shorten overall survival compared to combination regimens.

The addition of monoclonal antibodies like cetuximab and panitumumab in first-line treatment has not shown a significant improvement in overall survival, suggesting their use should be reconsidered, particularly in patients with KRAS mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer. [2013]

FOLFOXIRI treatment significantly improves response rates and progression-free survival in metastatic colorectal cancer patients compared to the standard FOLFIRI regimen, with odds ratios indicating a 2.04 times higher response rate and hazard ratios showing a 28% reduction in progression and death risk.

However, while FOLFOXIRI offers these benefits, it also comes with increased toxicity compared to FOLFIRI, although it does not significantly raise the risk of anemia, fatigue, or febrile neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity. Montagnani, F., Chiriatti, A., Turrisi, G., et al.[2018]

In a study of 115 patients with advanced gastric cancer, the combination of irinotecan, 5-fluorouracil (5-FU), and folinic acid (FA) showed a higher overall response rate of 42.4% and a median survival time of 10.7 months compared to 32.1% and 6.9 months for the irinotecan/cisplatin combination.

The irinotecan/5-FU/FA regimen had a better safety profile, with significantly lower rates of severe neutropenia (27% vs. 65.7%) compared to irinotecan/cisplatin, making it the preferred choice for further investigation in a phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Pozzo, C., Barone, C., Szanto, J., et al.[2020]

In a study of 154 patients with advanced colorectal cancer, three different regimens combining irinotecan (CPT-11) with 5-fluorouracil (5-FU) and folinic acid (FA) showed overall response rates of 33%, 42%, and 30%, indicating that all regimens were effective in treating the disease.

The biweekly regimen (arm B) was particularly noteworthy for having a significantly lower incidence of severe neutropenia (8% of patients) compared to the other regimens, while all three regimens had similar rates of severe delayed diarrhea (15% to 22%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II trial of irinotecan in combination with infusional or two different bolus 5-fluorouracil and folinic acid regimens as first-line therapy for advanced colorectal cancer. Bouzid, K., Khalfallah, S., Tujakowski, J., et al.[2020]

The combination of FOLFOXIRI and bevacizumab demonstrated a promising progression-free survival (PFS) rate of 74% at 10 months in patients with unresectable metastatic colorectal cancer, based on a phase 2 study involving 57 patients.

The treatment was found to be safe, with no unexpected adverse events reported, although common serious side effects included neutropenia and hypertension, indicating that while effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Masi, G., Loupakis, F., Salvatore, L., et al.[2022]

The bimonthly FOLFIRI regimen, combining irinotecan, folinic acid, and 5-fluorouracil, demonstrated efficacy in treating metastatic colorectal cancer, with a median survival time of 10.6 months and a median time to disease progression of 4.7 months among 19 patients.

The treatment was generally well-tolerated, with most non-hematological toxicities being mild (grade 1 or 2), and only a few cases of severe neutropenia, indicating a manageable safety profile for this chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRI chemotherapy for metastatic colorectal cancer patients. Kamnerdsupaphon, P., Lorvidhaya, V., Chitapanarux, I., et al.[2018]

In a study of 89 patients with advanced colorectal cancer, the combination of infusional 5-fluorouracil (5-FU) and oxaliplatin showed the best overall survival, with a median survival time of 17 months, compared to 15 months for bolus 5-FU and 11 months for 5-FU with CPT-11.

The results suggest that infusional 5-FU can be effectively used as a foundation for sequential chemotherapy regimens, particularly when combined with oxaliplatin, while CPT-11 alone did not provide sufficient efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mayo regimen plus three different second-line chemotherapy regimens in sequential therapy in patients with advanced colorectal cancer (ACRC). Popov, IP., Jelic, SB., Matijasevic, MM., et al.[2018]

Irinotecan has been shown to significantly prolong survival in patients with 5-FU-resistant colorectal cancer compared to best supportive care or 5-FU-based chemotherapy, based on Phase III studies.

Combining irinotecan with other treatments, such as raltitrexed or oral fluoropyrimidines, has shown promising results in terms of safety and efficacy, with response rates exceeding 30% and median survival benefits in various cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies. Armand, JP., Cunningham, D., van Cutsem, E., et al.[2019]

References

1. France pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer: fluorouracil plus folinic acid and irinotecan or oxaliplatin. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Epidemiology, treatment and chemoprevention in colorectal cancer. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer. [2013]

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

A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A randomized phase II trial of irinotecan in combination with infusional or two different bolus 5-fluorouracil and folinic acid regimens as first-line therapy for advanced colorectal cancer. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. [2022]

8. Thailand pubmed.ncbi.nlm.nih.gov

FOLFIRI chemotherapy for metastatic colorectal cancer patients. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Mayo regimen plus three different second-line chemotherapy regimens in sequential therapy in patients with advanced colorectal cancer (ACRC). [2018]

10. England pubmed.ncbi.nlm.nih.gov

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies. [2019]