Tislelizumab for Colorectal Cancer

Recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug tislelizumab (also known as Tizveni or Tevimbra) can effectively treat colorectal cancer in individuals living in Nigeria. It targets patients who have not received prior treatment and whose cancer exhibits a specific characteristic where cells cannot repair themselves properly, known as mismatch repair deficient (dMMR). The study will also assess the drug's safety for participants. Individuals with colorectal cancer that meets these criteria and who have not yet started treatment may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that tislelizumab is likely to be safe for humans?

Research has shown that tislelizumab has been tested in individuals with cancers similar to colorectal cancer, yielding promising safety results. In earlier studies, tislelizumab demonstrated an acceptable safety profile, with most side effects being manageable. For example, when combined with other treatments, side effects were generally mild for most patients.

Tislelizumab has already received approval for treating other cancer types, indicating it is usually well-tolerated. While it may cause side effects, they are unlikely to be severe for most individuals. However, experiences can vary, so discussing any concerns with the study team is important. ^{1 2 3 4 5}

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

Researchers are excited about Tislelizumab for colorectal cancer because it offers a new approach compared to traditional treatments like chemotherapy and targeted therapies. Tislelizumab is a monoclonal antibody that works by blocking the PD-1 pathway, which helps the immune system recognize and attack cancer cells more effectively. This mechanism is different from standard treatments, potentially leading to a more robust immune response against the cancer. Additionally, Tislelizumab is administered intravenously every three weeks, which could offer a more convenient schedule with manageable side effects for patients.

What evidence suggests that tislelizumab might be an effective treatment for colorectal cancer?

Research shows that tislelizumab might help treat certain types of colorectal cancer, particularly those that are "mismatch repair deficient" (dMMR). Studies have found that 25% of patients with this type of cancer experienced tumor shrinkage, known as a partial response. Immunotherapy, like tislelizumab, typically works better for dMMR cancers than for "microsatellite stable" (MSS) cancers. Therefore, for individuals with dMMR colorectal cancer, tislelizumab could be a promising treatment option. In this trial, all participants, whether in Cohort 1 with Stage 4 colorectal cancer or Cohort 2 with Stage 2/3 rectal cancer, will receive tislelizumab. ^{6 7 8 9 10}

Who Is on the Research Team?

Fiyinfolu Balogun

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

Hemoglobin >9 g/dL or ≥5.6 mmol/L

AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN (< 5 x ULN if hepatic metastases are present in cohort 1)

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11099463/

Chemoradiotherapy plus tislelizumab for mismatch repair ... CONCLUSION. We presented a rare case of pMMR advanced rectal cancer with distant lymph node metastasis treated with CRT and Tislelizumab with good efficacy.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e15644

Neoadjuvant chemoradiotherapy plus PD-1 inhibitor ... PD-1 inhibitors combined with chemoradiotherapy have shown preliminary efficacy in the neoadjuvant treatment of MSS rectal cancer.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625059437

1109 Radiotherapy followed by Systemic Therapy and ... The addition of radiotherapy may further improve the efficacy as it can overcome the hyporesponsiveness and decrease tumor burden. MIRACLE-2 aims to assess the ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00280-7/fulltext

65P BETTER study: An open-label, single-arm trial ... Therapeutic outcomes analysis revealed 4 patients (25.0%) achieved the best efficacy evaluation of partial response (PR), 10 patients (62.5%) demonstrated ...

5. nature.com nature.com/articles/s41467-024-51536-x

Tislelizumab plus cetuximab and irinotecan in refractory ... Immunotherapy confers little to no benefit in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)04270-3/fulltext

47P Safety and efficacy evaluation of long-course ... Tislelizumab added to long course NCRT followed by TME exhibited favorable pCR rate with manageable toxicities and postoperative complication.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06940388

Total Neoadjuvant Treatment With or Without Tislelizumab ... This is a prospective, multi-center, double arm, open-label, phase II randomized (1:1) controlled trial aimed to determine the efficacy and safety of TNT with ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT372422

Safety and efficacy evaluation of long course neoadjuvant ... Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3599

An open-label, single-arm, multicenter phase II study. Neoadjuvant TIS was associated with high MPR and pCR rates and an acceptable safety profile, and did not compromise surgery in pts with resectable MSI-H/dMMR ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9933500/

Interim result of phase II, prospective, single-arm trial of long ... This study aims to explore the safety and efficacy of long-course chemoradiotherapy combined with concurrent tislelizumab as a neoadjuvant treatment regimen