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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CYAD-101 for individuals with advanced colorectal cancer that cannot be surgically removed. The trial aims to assess the safety and effectiveness of CYAD-101 when administered after standard chemotherapy treatments, either FOLFOX or FOLFIRI. Ideal candidates for this trial are those whose colorectal cancer has spread and is unresponsive to previous treatments. As a Phase 1 trial, this research focuses on understanding how CYAD-101 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that CYAD-101 is generally safe and well-tolerated in people with advanced colorectal cancer. Earlier studies reported no serious side effects, such as graft-versus-host disease, which occurs when donated cells attack the body. Additionally, no severe side effects emerged that would prevent patients from continuing treatment.

Regarding the combination with FOLFIRI, past research on similar treatments has shown that using multiple drugs together can reduce some side effects, like hair loss and diarrhea, compared to using just one drug. This suggests that the combination is also generally safe.

Overall, both treatment combinations in these studies have demonstrated promising safety profiles, indicating they are unlikely to cause severe harm to patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CYAD-101 because it offers a novel approach to treating colorectal cancer by using engineered T cells. Unlike standard chemotherapy options like FOLFOX and FOLFIRI, CYAD-101 is a CAR-T cell therapy designed to enhance the immune system’s ability to target and destroy cancer cells. This treatment is particularly promising because it combines the precision of immunotherapy with traditional chemotherapy, potentially improving efficacy and reducing side effects. By harnessing the power of the immune system, CYAD-101 provides a new mechanism of action that sets it apart from the current standard of care.

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

Research has shown that CYAD-101, combined with FOLFOX chemotherapy, may effectively treat metastatic colorectal cancer. Earlier studies demonstrated that this combination helped CYAD-101 CAR T-cells, a type of immune cell engineered to attack cancer cells, successfully integrate into the body. This approach is a form of immunotherapy, which has shown benefits for colorectal cancer, particularly in patients with certain genetic traits. In this trial, one group of participants will receive CYAD-101 with FOLFOX.

Another group in this trial will receive CYAD-101 with FOLFIRI. Studies indicate that this treatment is often used when the first treatment fails. The mix of irinotecan and other drugs in FOLFIRI has extended the time patients live without their cancer worsening. These findings suggest that using CYAD-101 with these chemotherapies might improve overall effectiveness in fighting colorectal cancer. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19153116/

Efficacy of FOLFIRI-3 (irinotecan D1,D3 combined with LV5 ... In unselected patients pretreated with oxaliplatin, PFS in second line appeared to be improved by FOLFIRI-3 regimen.

2. northerncanceralliance.nhs.uk northerncanceralliance.nhs.uk/wp-content/uploads/2018/11/CR001FOLFIRI-CNTW-protocol-CRP09-CR001V1.4.pdf

FOLFIRI (Irinotecan / Modified De Gramont) Irinotecan combined with Fluorouracil compared with Fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21665462/

Single-agent irinotecan or FOLFIRI as second-line ... Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes.

4. researchgate.net researchgate.net/publication/23800832_Efficacy_of_FOLFIRI-3_irinotecan_D1D3_combined_with_LV5-FU_or_other_irinotecan-based_regimens_in_oxaliplatin-pretreated_metastatic_colorectal_cancer_in_the_GERCOR_OPTIMOX1_study

Efficacy of FOLFIRI-3 (irinotecan D1,D3 combined with LV5 ... Second-line irinotecan-based chemotherapy is commonly used in metastatic colorectal cancers after first-line oxaliplatin-based chemotherapy.

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1237764/pdf

Can immunotherapy reinforce chemotherapy efficacy? a ... Also, the results of studies have shown that the level of TP expression in tumor tissue is increased after exposure to radiotherapy and.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11927155/

Colorectal Cancer: Risk Factors, Novel Approaches in ... Abstract. By 2040 the burden of colorectal cancer will increase to 3.2 million new cases per year and 1.6 million deaths per year.

7. mdpi.com mdpi.com/2072-6694/17/17/2810

Advancements in Targeted Therapies for Colorectal Cancer Targeted therapies like cetuximab and panitumumab have improved outcomes for CRC patients with wild-type KRAS. However, resistance mechanisms and intra- and ...

8. revistafarmaciahospitalaria.es revistafarmaciahospitalaria.es/es-efficacy-safety-high-doses-irinotecan-articulo-S113063432300137X

Efficacy and safety of high doses of irinotecan in patients with ... The purpose of this systematic review is to analyze the published data on the efficacy and safety of doses higher than 180 mg/m2 of irinotecan recommended in ...