Neoplasms, Rectal
Conditions
Keywords
GSK4057190, Dostarlimab, dMMR, MSI-H, Locally advanced rectal cancer, DuraSTAR, PD-1, LARC, Anti-PD1
Brief summary
This study is conducted in adults with rectal cancer that has a certain genetic type. The main goal is to find out whether a longer treatment period with dostarlimab can help more participants have a complete response to treatment and avoid standard treatments like chemotherapy, radiation treatment, or surgery. Scans and endoscopy tests will be conducted to see if the tumor disappears and how long the cancer stays under control. The study will also collect information on side effects and health outcomes after dostarlimab.
Interventions
BIOLOGICALDostarlimab
Dostarlimab will be administered.
Sponsors
GlaxoSmithKline
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
* Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+) locally advanced rectal adenocarcinoma. * Has radiologically and endoscopically evaluable disease. * Has a tumor demonstrating the presence of either: 1. dMMR status; MMR status must be assessed by immunohistochemistry for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of 1 or more proteins indicates dMMR; MMR status will be determined locally; or 2. MSI-H phenotype as determined by polymerase chain reaction or by tissue next generation sequencing; MSI-H will be determined locally. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Has adequate organ function.
Exclusion criteria
* Has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer. * Has a tumor that, in the investigator's judgment, is causing symptomatic bowel obstruction or otherwise requires urgent/emergent local intervention. Participants with a history of bowel obstruction are eligible after obstruction is relieved by a diverting stoma (defunctioning colostomy). Patients with a history of bowel obstruction in the context of current rectal cancer diagnosis and treated with stenting are not eligible. * Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury within 28 days prior to enrollment. * Is receiving any other anticancer or experimental therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of participants who achieve clinical complete response (cCR) amongst participants who receive > 9 cycles (> 6 months) of dostarlimab monotherapy by investigator assessment | Up to 168 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall cCR rate by investigator assessment | Up to 171 weeks | Overall cCR rate is defined as the percentage of participants achieving cCR by investigator assessment at any disease assessment, regardless of duration of dostarlimab therapy among all enrolled participants. |
| Number of participants with sustained clinical complete response at 12 months (cCR12) as assessed by investigator | Up to 171 weeks | cCR12 is defined as achievement and maintenance of cCR for 12 months from the disease assessment after the last dose of study intervention that first demonstrates cCR by investigator assessment. |
| Objective response rate (ORR) as assessed by investigator | Up to 171 weeks | ORR is defined as the percentage of participants who achieve a best clinical response of partial response (PR), near complete response (nCR), or clinical complete response (cCR) at any disease assessment. |
| Number of participants with composite cCR12 and pathologic complete response (pCR) as assessed by investigator | Up to 171 weeks | The composite endpoint of cCR12 and pCR is defined as the number of participants who either achieve cCR12, or achieve pCR after receiving dostarlimab (before receiving standard of care) |
| Time to cCR | Up to 171 weeks | Time to cCR is defined as the time from the first dose of study intervention to the time of first cCR as assessed by the investigator. |
| Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), immune-mediated adverse event (imAEs), and AEs leading to death or discontinuation of study intervention by severity | Up to 171 weeks | — |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed