CYAD-101 + Chemotherapy and Immunotherapy for Colorectal Cancer

Recruiting at 5 trial locations

Overseen By Celyad Oncology Medical Monitor, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celyad Oncology SA

Must be taking: FOLFOX chemotherapy

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Uncontrolled illness, Pneumonitis, others

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

Compensation: Varies

Number of Visits: 15

Duration: 13 weeks

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with colorectal cancer that has spread and cannot be surgically removed. It combines an experimental therapy called CYAD-101 with standard chemotherapy and a type of immunotherapy. The trial aims to assess the safety and effectiveness of this combination. Suitable candidates have colorectal cancer that is inoperable, has metastasized, and has progressed after at least one prior treatment. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticancer agents and investigational agents at least 4 weeks before starting the study treatment. You also need to avoid certain growth factors and radiotherapy shortly before the trial begins. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

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

Earlier studies showed that the treatment CYAD-101, combined with FOLFOX chemotherapy and pembrolizumab, had promising safety results. Research shows that no patients experienced graft-versus-host disease, a serious condition where donor cells attack the body. Additionally, there were no reports of severe side effects related to the treatment. This suggests that the combination might be well-tolerated by patients. However, since this study is still in an early phase, more research is needed to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Researchers are excited about CYAD-101 for colorectal cancer because it introduces a novel approach by using engineered T cells. Unlike standard treatments like chemotherapy and targeted therapies, CYAD-101 is a type of immunotherapy that leverages the body's own immune system to fight cancer more effectively. It is combined with FOLFOX chemotherapy and pembrolizumab, which might enhance its effectiveness by creating a more favorable environment for the immune cells to attack the tumor. This combination aims to offer a more targeted and potentially less toxic treatment option compared to traditional therapies.

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

Research shows that CYAD-101, a new type of CAR T-cell therapy, may help treat advanced colorectal cancer. Early findings suggest it is safe and patients tolerate it well. This treatment uses immune cells modified to better locate and attack cancer cells. In this trial, participants will receive CYAD-101 with FOLFOX, a common chemotherapy mix for colorectal cancer that has been shown to extend survival. Studies have demonstrated that FOLFOX works well when combined with other treatments. Following this, participants will receive Pembrolizumab, an immunotherapy effective in some colorectal cancers, especially those with certain genetic traits. It enhances the immune system's ability to fight cancer cells. Together, these treatments aim to provide a comprehensive approach to fighting cancer. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with metastatic colorectal cancer that's not been surgically removed and doesn't respond to standard treatments. Participants must have had FOLFOX chemotherapy, be in good physical condition (ECOG 0 or 1), and have tumors measurable by RECIST criteria. They can't join if they've used certain growth factors, had major surgery, uncontrolled illnesses, live vaccines, anticancer agents or radiotherapy recently; or if they've ever received drugs like Pembrolizumab before.

Inclusion Criteria

My tumor does not have high microsatellite instability.

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

Unequivocal and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)

Exclusion Criteria

I have been treated with specific immune therapy drugs before.

I have not had radiotherapy in the last 2 weeks.

Any other investigational agent or device within 4 weeks of the first study treatment administration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

CYAD-101 is administered concurrently with FOLFOX chemotherapy, followed by pembrolizumab treatment

13 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CYAD-101
• FOLFOX
• Pembrolizumab

Trial Overview The study tests CYAD-101 cells given with FOLFOX chemo followed by Pembrolizumab immunotherapy in patients with advanced colorectal cancer. It aims to see how safe this combination is and whether it works against the cancer.

How Is the Trial Designed?

Group I: CYAD-101 with FOLFOX Infusion administered concurrently followed by pembrolizumab Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Celyad Oncology SA

Lead Sponsor

Trials

13

Recruited

1,300+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

A novel vaccine combining irradiated human colon cancer cells and GM-CSF-producing cells was found to be safe and feasible in a phase 1 study involving nine patients with metastatic colorectal cancer.

Patients who had undergone curative metastasectomy showed promising outcomes, with six surviving longer than 36 months and four remaining disease-free, suggesting potential benefits of the vaccine in enhancing anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety and feasibility study of an allogeneic colon cancer cell vaccine administered with a granulocyte-macrophage colony stimulating factor-producing bystander cell line in patients with metastatic colorectal cancer. Zheng, L., Edil, BH., Soares, KC., et al.[2021]

Immunotherapy for colorectal cancer has shown potential benefits in some clinical trials, but it is still considered an experimental treatment rather than a standard option.

The review discusses various immunotherapeutic strategies, such as cancer vaccines and adoptive cell therapy, highlighting their strengths and weaknesses, and aims to guide future research towards the approval and use of these therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer immunotherapy. Xiang, B., Snook, AE., Magee, MS., et al.[2022]

Immunotherapy, particularly PD-1 and PD-L1 inhibitors, has shown limited effectiveness in treating unselected metastatic colorectal cancer, with only a small subset of patients (about 5%) benefiting due to specific tumor characteristics.

Current research is exploring various combination therapies, but randomized data have not shown significant improvements in outcomes, indicating that the role of immunotherapy in colorectal cancer treatment is still being defined through ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in colorectal cancer: Available clinical evidence, challenges and novel approaches. Tintelnot, J., Stein, A.[2020]

Immunotherapy shows promise in treating colorectal cancer, with agents like the monoclonal antibody 17-1A and anti-EGFR antibodies demonstrating the immune system's ability to target and destroy cancer cells.

Clinical trials are currently evaluating various immunotherapeutic strategies, including dendritic cell vaccines and anti-idiotypic antibodies, with some showing potential to enhance anti-tumor responses, although challenges remain due to tumor evasion mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current concepts in immunotherapy for the treatment of colorectal cancer. Indar, A., Maxwell-Armstrong, CA., Durrant, LG., et al.[2019]

Immune checkpoint inhibitors (ICIs) like anti-CTLA-4 and anti-PD-1/PD-L1 have revolutionized cancer treatment, showing promise in various cancers, but not all patients respond, and some develop resistance.

ICIs can cause immune-related adverse effects (irAEs) that vary in severity and can be fatal, highlighting the need for clinicians to recognize and manage these toxicities effectively as they differ from traditional cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting tumor responders and predictive biomarkers of toxicities in cancer patients treated with immune checkpoint inhibitors. Yao, L., Jia, G., Lu, L., et al.[2021]

In a study of 100 patients undergoing chemoradiotherapy for localized anal cancer, patient-reported outcomes (PROs) indicated a higher incidence of acute toxicity compared to physician-assessed toxicity (CTCAE), highlighting the importance of incorporating PROs in evaluating treatment effects.

Proton therapy demonstrated superior dosimetric planning compared to IMRT and VMAT, suggesting it may reduce radiation exposure to surrounding healthy tissues, potentially leading to lower toxicity in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization. Kronborg, C., Serup-Hansen, E., Lefevre, A., et al.[2019]

The combination of immune checkpoint inhibitors (ICIs) and chemotherapy significantly increases the risk of gastrointestinal adverse events (AEs) in cancer patients, with specific risks including diarrhea and colitis associated with PD-1 inhibitors, nausea with PD-L1 inhibitors, and decreased appetite and severe diarrhea with CTLA-4 inhibitors.

This systematic review and meta-analysis included 10 trials with 5,142 patients, highlighting the need for clinicians to be vigilant about these gastrointestinal toxicities when using ICI plus chemotherapy in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Gastrointestinal Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Systematic Review and Meta-Analysis. Yang, W., Men, P., Xue, H., et al.[2020]

In a phase II study involving 24 previously untreated patients with metastatic colorectal carcinoma, acivicin was administered as a 72-hour continuous infusion, resulting in mild to moderate toxicity primarily characterized by gastrointestinal symptoms and central nervous system changes.

The study found no effective responses in the 23 evaluable patients, indicating that acivicin, as given in this trial, is not an effective treatment for colorectal carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of acivicin as a 72-hr continuous infusion in patients with untreated colorectal cancer. A National Cancer Institute of Canada Clinical Trials Group Study. Eisenhauer, EA., Maroun, JA., Fields, AL., et al.[2019]

In a study of 3,758 advanced gastric cancer patients treated with S-1, the drug demonstrated a manageable safety profile, with neutropenia being the most common severe side effect occurring in only 6.3% of patients during short-term treatment.

S-1 allowed for good treatment compliance over time, with a low incidence of severe adverse events (0.3-3.8%) and no significant difference in severe event onset between patients with mild renal impairment and those with normal kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of oral fluoropyrimidine S-1 for short- and long-term delivery in advanced gastric cancer: analysis of 3,758 patients. Yamanaka, T., Matsumoto, S., Teramukai, S., et al.[2013]

Immunotherapy, particularly with novel checkpoint inhibitors, shows promise for treating metastatic colorectal cancer (mCRC), especially in patients with microsatellite instability-high (MSI-H) tumors, which have received FDA breakthrough designation for this treatment.

Despite the potential of checkpoint inhibitors, many patients with MSI-H and nearly all with microsatellite stable disease do not respond to these therapies, prompting ongoing clinical trials to explore better patient selection and combination strategies to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Expanding Role for Immunotherapy in Colorectal Cancer. Bever, KM., Le, DT.[2022]

Recent advancements in predicting colon cancer recurrence risk include the use of microsatellite instability (MSI) and gene expression profiles, which can help guide treatment decisions, especially in stage II and low-risk stage III patients.

Standard adjuvant therapy for most stage III colon cancer patients involves a combination of oxaliplatin with 5-FU (FOLFOX) or capecitabine (XELOX), but ongoing studies are exploring the efficacy of reducing treatment duration to 3 months to minimize neurotoxicity while maintaining effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy of stage III colon cancer. Sun, W., Haller, DG.[2015]

Supplementing mice with Lactobacillus rhamnosus GG (LGG) significantly increased CD8 T-cell responses in the gut, which is crucial for enhancing antitumor immune responses.

LGG administration led to a reduction in tumor burden in murine models of intestinal cancer, demonstrating its potential to improve the effectiveness of immunotherapy in colorectal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response. Owens, JA., Saeedi, BJ., Naudin, CR., et al.[2022]

Adjuvant therapy using 5-fluorouracil and levamisole for node-positive colon cancer, and chemoradiotherapy with 5-fluorouracil and high-dose radiotherapy for stage II or III rectal cancer, significantly reduces recurrence and mortality, improving overall survival by over 30%.

Ongoing trials are exploring various combinations and durations of chemotherapy and radiotherapy, as well as the potential of aspirin for colon cancer prevention, indicating a shift towards more personalized and effective treatment strategies for colorectal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant treatment of colorectal adenocarcinoma. Steele, G., Posner, MR.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.74

Updated data from alloSHRINK phase I first-in-human ... KEYNOTE-B79 phase 1b trial to evaluate the allogeneic CAR T-cells CYAD-101 and pembrolizumab in refractory metastatic colorectal cancer patients ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3032

CYAD-101: An innovative non-gene edited allogeneic CAR ... Conclusions: These early clinical results demonstrate the safety and tolerability of a non-gene edited predominantly CD4+ CAR-T therapeutic ...

3. celyad.com celyad.com/wp-content/uploads/Celyad_SITC2019_poster_P330_ALLOSHRINK.pdf

Results from the completed dose-escalation of the ... The objective of this study is to evaluate if the FOLFOX chemotherapy can ensure the engraftment of the allogeneic CYAD-101 CAR T-cells. ○ The patient ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04991948

NCT04991948 | Study of Pembrolizumab Treatment After ... The purpose of the CYAD-101-002 study is to assess the safety and clinical activity of CYAD-101 in patients with unresectable metastatic colorectal cancer ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9705989/

CAR T-cells for colorectal cancer immunotherapy CAR T-cell therapy for colorectal cancer is still in its early stages, and clinical data are scarce. Major limitations of this therapy include high toxicity, ...

6. cancernetwork.com cancernetwork.com/view/fda-lifts-clinical-hold-on-trial-assessing-cyad-101-plus-pembrolizumab-and-folfox-in-advanced-crc

FDA Lifts Clinical Hold on Trial Assessing CYAD-101 Plus ... The FDA has lifted a clinical hold that was placed on the phase 1b CYAD-101-002 trial (NCT04991948), assessing the use of pembrolizumab ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT354801

KEYNOTE-B79 phase 1b trial to evaluate the allogeneic ... KEYNOTE-B79 phase 1b trial to evaluate the allogeneic CAR T-cells CYAD-101 and pembrolizumab in refractory metastatic colorectal cancer patients. download.

8. onclive.com onclive.com/view/fda-places-clinical-hold-on-keynote-b79-trial-examining-car-t-cell-therapy-cyad-101-in-metastatic-crc

FDA Places Clinical Hold on KEYNOTE-B79 Trial ... Regarding safety, no graft-versus-host disease was observed, nor were there any grade 3 or higher treatment-related toxicities. The recommended ...