A Phase 2, Single-Arm, Open-Label Study with Dostarlimab Monotherapy in Participants with Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer

Phase 2

Recruiting

• Conditions: rectal cancer; 10017990

• Registration Number: NL-OMON56158
• Lead Sponsor: GlaxoSmithKline

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

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 dMMR; 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
ECPAM) 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.
6. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and if a woman of child bearing potential (WOCBP), is using a
contraceptive method that is highly effective
7. Has an ECOG performance status of 0 or 1.
8. Has adequate organ function, as defined in Table 8 of the protocol.

Exclusion Criteria

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, see protocol 5.2.1. item 6 for details.
7. Is unable to undergo MRI.
8. Has experienced any of the following with prior immunotherapy: see protocol
5.1.1. item 8 for details
9. Has undergone any major surgical procedure, open biopsy, or experienced
significant traumatic injury within 28 days prior to enrollment.
10. Has any history of interstitial lung disease or pneumonitis.
11. Has cirrhosis or current unstable liver or biliary disease per investigator
assessment, see protocol 5.2.1. item 11 for details.
12. Has a history or current evidence of any medical condition, therapy, or
laboratory abnormality that might confound the study results, interfere with
participation for the full duration of the study intervention, or indicate it
is not in the best interest of the participant to participate, in the opinion
of the investigator.
13. Has a history of or evidence of cardiac abnormalities such as serious,
uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
within the 6 months prior to enrollment, see protocol 5.2.1. item 14 for
details.
14. Is receiving any other anticancer or experimental therapy, see protocol
5.2.1. item 15 for details.
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, see protocol
5.2.1. item 17 for details.
17. Has received any live vaccine within 30 days prior to enrollment. see
protocol 5.2.1. item 18 for details.
18. Has received or plans to receive an organ or stem cell transplant that uses
donor stem cells (allogeneic stem cell transplant)
19. Has documented presence of HBsAg at Screening, a positive HCV antibody test
result at Screening , a positive HCV RNA test result at Screening ,
20. a known history of HIV infection, see protocol 5.2.1. item 19, 20, 21 & 22
for details.
For a detailed list of Exclusion Criteria please refer to the protocol section
5.2.1.

Study & Design

• Study Type: Interventional
• Study Design: Not specified