Colorectal Cancer
Conditions
Brief summary
The main purpose of this study was to help meet the medical needs of people in China with certain types of solid tumors that have specific genetic changes called microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). The study looked at how well the drug tislelizumab works and how safe it is when given before surgery (neoadjuvant treatment) for these types of tumors.
Detailed description
This study enrolled participants with Stage II or III resectable colorectal cancer (CRC). Participants with unknown microsatellite instability (MSI) or mismatch repair (MMR) status provided blood and tumor tissue samples during a prescreening period (within 56 days before the first dose) for central laboratory confirmation of MSI status. Participants with known MSI-high (MSI-H) or deficient MMR (dMMR) status by local laboratory also underwent central confirmation when tumor samples were available. Eligible participants received tislelizumab 200 mg by intravenous infusion once every 3 weeks for 3 cycles as neoadjuvant therapy. After completion of neoadjuvant treatment, participants underwent complete surgical removal (R0 resection) of their tumor, and surgical specimens were assessed for pathological response, including major pathological response (MPR) and pathological complete response (pCR). Post-surgery, participants continued adjuvant therapy and follow-up as determined by their investigator.
Interventions
DRUGTislelizumab
200 milligrams (mg) administered through an intravenous (IV) infusion once every 3 weeks for 3 treatment cycles
Sponsors
BeiGene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants had an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. * Participants had a pathologically (histologically) confirmed diagnosis of potentially resectable Stage II or Stage III colon or rectal cancer (CRC) with microsatellite instability-high (MSI-H) status confirmed by a sponsor-designated central laboratory, or known MSI-H status confirmed by a local laboratory. Participants were required to be eligible for complete surgical removal of the tumor (R0 resection) with curative intent. * Participants had evaluable or measurable disease as assessed by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. * Participants had adequate blood counts and organ function, as defined by protocol-specified laboratory test results obtained within 7 days before the first dose of study treatment.
Exclusion criteria
* Participants had received any prior treatment for their current colorectal cancer, including chemotherapy, radiotherapy, or immunotherapy. * Participants had any condition requiring systemic treatment with corticosteroids at doses greater than 10 milligrams (mg) of prednisone per day, or other immunosuppressive medications within 14 days before the first dose. * Participants had active autoimmune diseases or a history of autoimmune diseases that could potentially relapse. Note: Additional protocol-defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) Rate | Approximately 10 weeks after first dose of study treatment | MPR rate is defined as the percentage of participants whose resected primary tumor shows 10% or less remaining viable cancer cells after completing neoadjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | Approximately 10 weeks after first dose of study treatment | Defined as the percentage of participants with a complete absence of residual tumor (no remaining cancer cells) in the surgically resected primary tumor and in all resected lymph nodes after completing neoadjuvant therapy. |
| Event Free Survival (EFS) | From first dose to final analysis data cutoff (03JAN2025), disease progression, initiation of a new anticancer therapy, or death; whichever came first. Median follow-up was 21.7 months. | Defined as the time from the first dose of study treatment until the first occurrence of any of the following events: * Disease progression that prevents complete surgical remover of the tumor * Local or distant recurrence after surgery * Death from any cause The median and other quartiles of EFS were estimated using the Kaplan-Meier Method. |
| 2-Year and 3-Year Event Free Survival (EFS) | 24 months and 36 months after first dose | The 2-year and 3-year EFS rates are defined as the percentage of participants without any EFS events at 24 months and 36 months after the first dose. EFS rates were estimated by the Kaplan-Meier method with 95% CI estimated using Greenwood's formula. |
| Number of Participants Experiencing Adverse Events | From the first dose until 30 days (or 90 days for imAEs) after the last dose of tislelizumab, death, or start of new anticancer therapy, whichever occurred first (up to 03JAN2025). Maximum treatment duration was 2.3 months. | The incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and immune-mediated adverse events (imAEs), was assessed for all participants who received at least one dose of study treatment. SAEs were defined as events that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability, or were considered important medical events. imAEs were defined as adverse events consistent with immune-related mechanisms, such as autoimmune-like toxicities requiring clinical evaluation or immunosuppressive management. |
Countries
China
Participant flow
Recruitment details
Participants were enrolled in multiple study centers in China.
Pre-assignment details
This study consisted of a screening phase (and/or prescreening phase) and a treatment phase that included a neoadjuvant phase, surgery, and a disease follow-up phase.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 16.3 |
| Race/Ethnicity, Customized Chinese | 33 Participants |
| Region of Enrollment China | 33 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 14 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (fully Active) | 27 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 1(Restrictive but Ambulatory) | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 33 |
| other Total, other adverse events | 31 / 33 |
| serious Total, serious adverse events | 4 / 33 |
Outcome results
None listed