Phase 2 Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer

Phase 1

• Conditions: ntreated Stage II/III dMMR/MSI-H locally advanced rectal cancer; MedDRA version: 21.0Level: PTClassification code 10038049Term: Rectal cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10038050Term: Rectal cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2022-003289-18-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-01-03
• Last Update Posted: 16 October 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Inclusion criteria
Inclusion criteria (Prescreening Period)
A Prescreening Period will only be available at sites/countries where
local dMMR/MSI-H testing is not available. The Prescreening Period is
not required for participants whose dMMR/MSI-H status has been previously determined. Prior to Screening, participants without must meet the Prescreening criteria below. To be eligible for participation in the study, participants must meet the full inclusion and exclusion criteria presented in Section 5.1.2 and Section 5.2, respectively, after completing the Prescreening Period.
Age
1. Is at least 18 years of age (or the local legal age of consent) at the
time of signing the ICF.
Type of participant and disease characteristics
1. Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+),
locally advanced rectal adenocarcinoma.
2. Has radiologically and endoscopically evaluable disease.
Inclusion criteria (Screening Period)Participants are eligible to be
included in the study only if all the following criteria apply:
Age
1. Is at least 18 years of age (or the local legal age of consent) at the
time of signing the ICF.
2. Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+),
locally advanced rectal adenocarcinoma.
3. Has radiologically and endoscopically evaluable disease.
4. Has a tumor demonstrating the presence of either:
a. dMMR status; MMR status must be assessed by IHC for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of 1 or more proteins indicates MMR; MMR status may be determined either locally or by the central reference laboratory; or
b. MSI-H phenotype as determined by polymerase chain reaction or by tissue next generation sequencing; MSI-H may be determined locally.
NOTE: Participants who are known to have Lynch syndrome and have
been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2,or EPCAM) may be eligible to participate.
5. Has an archival FFPE tissue sample that must be available and
submitted to the central reference laboratory for testing at Screening. If no archival tissue is available, a fresh baseline biopsy will be required.
8. Has an ECOG performance status of 0 or 1.
9. Has adequate organ function, as defined in Table 8. (NOTE: A
complete blood count test should be obtained without transfusion or
receipt of colony-stimulating factors within 2 weeks of obtaining the
sample.)
For a full list of Inclusion criteria please refer to the Study Protocol
Section 5.1 Inclusion Criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

Exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
Medical conditions
1. Has distant metastatic disease.
2. Has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer. Note: Endoscopy guided biopsy is not considered surgery.
3. Has a tumor that, in the investigator's judgment, is causing symptomatic bowel obstruction or otherwise requires urgent/emergent local intervention.
4. Has a known additional malignancy that progressed or required active treatment within the past 2 years. Exceptions include adequately treated superficial skin cancers, superficial bladder cancers, and other in situ cancers.
5. Is immunocompromised in the opinion of the investigator.
6. Has an active autoimmune disease that has required systemic
treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, orimmunosuppressive 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.
8. Has experienced any of the following with prior immunotherapy: any irAE of Grade =3, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain- Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary.
9. Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury within 28 days prior to
enrollment.
15. Is receiving immunosuppressive medication.
16. Has received systemic corticosteroids (>10 mg daily prednisone or
equivalent) within 7 days of first dose of study intervention. Use of
inhaled steroids, local injection of steroids, topical steroids, and
steroidal eye drops are allowed.
18. Has received or plans to receive an organ or stem cell transplant that uses donor stem cells (allogeneic stem cell transplant).
For a full list of Exclusion criteria please refer to the Study Protocol
Section 5.2

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified