Clinical trial NCT05723562: A Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Neoplasms, Rectal
Keywords: JEMPERLI
dostarlimab-gxly
GSK4057190A
Stage II/III rectal cancer
Neoadjuvant
dMMR
MSI-H
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-02-10
Enrollment: 154
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 purpose of this study is to investigate dostarlimab monotherapy in participants with locally advanced Mismatch-repair deficient (dMMR)/Microsatellite instability-high (MSI-H) rectal cancer who have received no prior treatment. Participants who achieve complete clinical response (cCR) following dostarlimab treatment will undergo non-operative management (NOM), including close surveillance for recurrent disease. The goal of the study is to determine if Dostarlimab therapy alone is an effective treatment that can allow participants to avoid chemotherapy, radiation, and surgery.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Participant has distant metastatic disease.
* Participant has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer.
* Participant has any history of interstitial lung disease or pneumonitis
* Participant 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.
* Participant 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.
* Participant 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.
* Participant has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or has known allergies to dostarlimab or its excipients.
* Has received or plans to receive an organ or stem cell transplant that uses donor stem cells (allogeneic stem cell transplant).

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 74 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 33 Weeks
measure: Objective Response Rate (ORR) as assessed by Investigator
timeFrame: Up to 33 Weeks
measure: Organ Preservation Rate
timeFrame: 3 years
measure: Disease-Specific Survival (DSS)
timeFrame: Up to 74 months
measure: Disease-Specific Response at 5 years (DSS5)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 74 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) based on Severity
timeFrame: Up to 74 months
measure: Number of Participants with discontinuation of study intervention
timeFrame: Up to 24 weeks
measure: Serum concentration of Dostarlimab
timeFrame: Up to 37 weeks
measure: Concentration at the end of infusion (C-EOI) of Dostarlimab
timeFrame: Up to 37 weeks
measure: Trough Concentration (C-trough) of Dostarlimab
timeFrame: Up to 37 weeks
measure: Number of Participants with Anti-Drug Antibodies against Dostarlimab
timeFrame: Up to 37 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Whittier
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Sioux Falls
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: BesanCon cedex
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Pessac cedex
country: France
facility: GSK Investigational Site
city: Rennes
country: France
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Dresden
country: Germany
facility: GSK Investigational Site
city: Duesseldorf
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Leeds West Yorkshire
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Sutton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: