Clinical trial NCT06640049: A Study of Dostarlimab in Participants With Untreated Locally Advanced Rectal Cancer in China
Official title: 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 in China
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neoplasms, Rectal
Keywords: Dostarlimab
GSK4057190A
TSR-042
Rectal cancer
dMMR
MSI-H
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-10-15
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main goal of this study is to evaluate the effect of dostarlimab monotherapy in Chinese participants with locally advanced Mismatch-repair deficient (dMMR)/ Microsatellite instability-high (MSI-H) rectal cancer who have received no prior treatment.


Eligibility criteria: Inclusion Criteria:

* Participant has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+), locally advanced rectal adenocarcinoma
* Participant has radiologically and endoscopically evaluable disease
* Participant has a tumor which can be categorized as dMMR or MSI-H by central assessment

Exclusion Criteria:

* Participant has distant metastatic disease
* Participant has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer
* Has a known additional malignancy that progressed or required active treatment within the past 2 years
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* Has experienced any of the following with prior immunotherapy: any irAE ≥ 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 \[SJS (Stevens-Johnson Syndrome, TEN (Toxic Epidermal Necrolysis), DRESS (Drug rash with eosinophilia and systemic symptoms)\], or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary
* Has any history of interstitial lung disease or pneumonitis
* Has received or plans to receive an organ or stem cell transplant that uses donor stem cells (allogeneic stem cell transplant)
* Has a history of severe allergic and/or anaphylactic reactions to chimeric, human, or humanized antibodies, fusion proteins, or known allergies to dostarlimab, or its excipients

Primary outcomes:
measure: Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR)
timeFrame: 18 months
Secondary outcomes:
measure: Number of Participants with Sustained Complete Clinical Response for 24 Months (cCR24) as assessed by ICR
timeFrame: 30 months
measure: Number of Participants with Sustained Complete Clinical Response for 36 Months (cCR36) as assessed by ICR
timeFrame: 42 months
measure: Number of Participants with Event Free Survival at 3 years (EFS3) as assessed by Investigator
timeFrame: 3 years
measure: Event Free Survival (EFS) as assessed by Investigator
timeFrame: Up to approximately 77 months
measure: Number of Participants with cCR12 as assessed by Investigator
timeFrame: 18 Months
measure: Number of Participants with cCR24 as assessed by Investigator
timeFrame: 30 Months
measure: Number of Participants with cCR36 as assessed by Investigator
timeFrame: 42 Months
measure: Objective Response Rate (ORR) assessed by ICR
timeFrame: Up to 37 Weeks
measure: Objective Response Rate (ORR) as assessed by Investigator
timeFrame: Up to 37 Weeks
measure: Organ Preservation Rate
timeFrame: Up to 3 years
measure: Disease-Specific Survival (DSS)
timeFrame: Up to approximately 77 months
measure: Disease-Specific Response at 5 years (DSS5)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 77 months
measure: Overall Survival at 5 years (OS5)
timeFrame: Up to 5 years
measure: Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Immune related Adverse Events (irAEs) and AEs leading to death or discontinuation of study intervention.
timeFrame: Up to approximately 77 months
measure: Serum concentration of Dostarlimab
timeFrame: Up to approximately 77 months
measure: Concentration at the end of infusion (C-EOI) of Dostarlimab
timeFrame: Up to approximately 77 months
measure: Trough Concentration (C-trough) of Dostarlimab
timeFrame: Up to approximately 77 months
measure: Number of Participants with Anti-Drug Antibodies (ADA) against Dostarlimab
timeFrame: Up to approximately 77 months
Other outcomes:
Locations:
city: Chengdu
country: China
facility: GSK Investigational Site
city: Chongqing
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Hangzhou
country: China
facility: GSK Investigational Site
city: Jinan
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Taiyuan
country: China
facility: GSK Investigational Site
Study officials:
References: