Tislelizumab for Colorectal Cancer

Recruiting at 2 trial locations

Overseen By Peter Kingham, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Active malignancy, Autoimmune disease, Hepatitis, AIDS, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving other anticancer or experimental therapy, or if you have been on certain immunosuppressive therapies recently.

What data supports the effectiveness of the drug Tislelizumab for colorectal cancer?

Research on similar drugs like atezolizumab, which targets the same cancer-immunity pathway, shows promising results in a small group of colorectal cancer patients with specific genetic traits (dMMR). This suggests that Tislelizumab might also be effective for similar patients. ^{1 2 3 4 5}

How is the drug Tislelizumab different from other treatments for colorectal cancer?

Tislelizumab is unique because it is a modified antibody that targets PD-1, a protein that helps cancer cells evade the immune system, and it is specifically engineered to reduce unwanted interactions with other immune cells, potentially improving its effectiveness and safety compared to other similar drugs. ^{3 6 7 8 9}

What is the purpose of this trial?

The researchers are doing this study to find out whether tislelizumab is an effective treatment for people with colorectal cancer who are living in Nigeria. The researchers will also look at the safety of the study drug. All participants in this study will be treatment naïve (they have not yet received treatment for their cancer), and their cancer will be mismatch repair deficient (dMMR). dMMR cancer can happen when your cells are unable to repair mistakes made during the cell division process.

Research Team

Fiyinfolu Balogun

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals in Nigeria with colorectal cancer who have not yet received treatment. Participants must have a specific type of cancer known as mismatch repair deficient (dMMR), which means their cells struggle to fix errors that occur when they divide.

Inclusion Criteria

Negative pregnancy test done within 72 hours prior to start of treatment for women of childbearing potential

I am using effective birth control and have a negative pregnancy test.

Hemoglobin >9 g/dL or ≥5.6 mmol/L

Exclusion Criteria

I have not needed systemic therapy for an autoimmune disease in the last 2 years.

I have been treated with drugs that boost the immune system.

I have active brain metastasis or carcinomatous meningitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tislelizumab at a dose of 200mg IV over 30 minutes (60 minutes at the initial infusion), every 3 weeks

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Tislelizumab

Trial Overview The study is testing the effectiveness and safety of tislelizumab, a potential new treatment for colorectal cancer. All participants will receive this medication to see how well it works against their dMMR colorectal cancer.

Participant Groups

Group I: Cohort 2: Stage 2/3 Rectal cancer Experimental Treatment 1 Intervention

All patients in the trial will be given Tislelizumab at a dose of 200mg IV over 30 minutes (60 minutes at the initial infusion), every 3 weeks.

Group II: Cohort 1: Stage 4 Colorectal cancer Experimental Treatment 1 Intervention

All patients in the trial will be given Tislelizumab at a dose of 200mg IV over 30 minutes (60 minutes at the initial infusion), every 3 weeks.

Tislelizumab is already approved in European Union, United States for the following indications:

Approved in European Union as Tizveni for:

• Non-small cell lung cancer (first and second line)
• Locally advanced or metastatic esophageal squamous cell carcinoma (second line)

Approved in United States as Tevimbra for:

• Unresectable or metastatic esophageal squamous cell carcinoma (second line)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

BeiGene USA, Inc.

Industry Sponsor

Trials

5

Recruited

490+

Findings from Research

The combination of pexastimogene devacirepvec (PexaVec) with durvalumab and tremelimumab was found to be safe and tolerable in patients with chemotherapy-refractory metastatic colorectal cancer, with no unexpected toxicities reported during the trial involving 34 patients.

While the median progression-free survival was similar between the two treatment cohorts (2.3 months for PexaVec/durvalumab/tremelimumab and 2.1 months for PexaVec/durvalumab), the treatment did show potential clinical activity, warranting further investigation into predictive biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of PexaVec in combination with immune checkpoint inhibition in refractory metastatic colorectal cancer. Monge, C., Xie, C., Myojin, Y., et al.[2023]

In a phase 2 study involving 218 patients with previously untreated metastatic colorectal cancer, the addition of atezolizumab to the standard chemotherapy regimen (FOLFOXIRI plus bevacizumab) significantly improved median progression-free survival to 13.1 months compared to 11.5 months in the control group.

The treatment was found to be safe, with the most common serious side effects being neutropenia and diarrhoea, although there were two treatment-related deaths in the atezolizumab group, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. Antoniotti, C., Rossini, D., Pietrantonio, F., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, shows promising efficacy in treating metastatic colorectal cancer (mCRC), particularly in patients with deficient mismatch repair (dMMR), indicating a potential new treatment avenue for this subgroup.

Ongoing clinical trials suggest that atezolizumab may be even more effective when combined with chemotherapy or targeted therapies, such as the MEK inhibitor cobimetinib, paving the way for its inclusion in future treatment protocols for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Tapia Rico, G., Price, TJ.[2022]

In a phase 2 clinical trial involving 133 patients with refractory metastatic colorectal cancer, the addition of atezolizumab to capecitabine and bevacizumab therapy resulted in a median progression-free survival (PFS) of 4.4 months compared to 3.6 months for the placebo group, indicating a potential benefit, although not clinically meaningful.

Patients with microsatellite-stable disease and those without liver metastasis showed greater benefits from the combination therapy, suggesting that specific patient characteristics may influence the efficacy of atezolizumab in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. Mettu, NB., Ou, FS., Zemla, TJ., et al.[2022]

In the final analysis of the KEYNOTE-164 study, pembrolizumab demonstrated a 32.8% objective response rate in patients with advanced MSI-H/dMMR colorectal cancer who had received multiple prior treatments, indicating its efficacy in this difficult-to-treat population.

The treatment was associated with a median overall survival of 31.4 months for patients with more prior therapies and 47.0 months for those with fewer, while maintaining a manageable safety profile with no new safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164. Le, DT., Diaz, LA., Kim, TW., et al.[2023]

Tislelizumab is a modified PD-1 antibody that effectively inhibits tumor growth in various cancers, including Hodgkin's lymphoma and lung cancer, and has received multiple approvals in China for its use.

It has a favorable safety profile with common side effects like fatigue and anemia, and it offers economic advantages over other PD-1 inhibitors, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. Zhang, L., Geng, Z., Hao, B., et al.[2023]

In a phase 3 trial involving 332 patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC), the combination of tislelizumab and chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 9.7 months versus 7.6 months.

The addition of tislelizumab also resulted in higher response rates and longer duration of response, making it a promising first-line treatment option for patients with advanced nsq-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. Lu, S., Wang, J., Yu, Y., et al.[2021]

In a phase II study with 70 patients suffering from relapsed/refractory classical Hodgkin lymphoma, tislelizumab showed a high overall response rate of 87.1% and a complete response rate of 67.1% after a median follow-up of 33.8 months, indicating its efficacy as a treatment option.

The treatment demonstrated a favorable safety profile, with 97.1% of patients experiencing treatment-related adverse events, but only 31.4% having severe (grade ≥3) events, and just 8.6% discontinuing treatment due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. Song, Y., Gao, Q., Zhang, H., et al.[2023]

In a study of 115 patients with recurrent or metastatic cervical cancer treated with tislelizumab, the overall response rate was 39.1%, and the median progression-free survival was 19.6 months, indicating promising antitumor activity.

Baseline serum C-reactive protein (CRP) levels and the CRP-to-albumin ratio (CAR) were identified as independent risk factors for predicting the efficacy and prognosis of tislelizumab treatment, with higher levels associated with shorter progression-free and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. Zheng, X., Gu, H., Cao, X., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I/II study of PexaVec in combination with immune checkpoint inhibition in refractory metastatic colorectal cancer. [2023]

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

Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]

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

Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. [2022]

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

Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164. [2023]

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

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]

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

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. [2021]

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

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. [2023]