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A Study of Dostarlimab in Participants With Untreated Locally Advanced Rectal Cancer in China

Phase 2
Recruiting
Conditions
Neoplasms, Rectal
Interventions
Registration Number
NCT06640049
Lead Sponsor
GlaxoSmithKline
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
23
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Dostarlimab monotherapyDostarlimabParticipants will receive dostarlimab as monotherapy.
Primary Outcome Measures
NameTimeMethod
Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR)18 months

cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by Independent central review (ICR) for 12 months from the first disease assessment after last dose of study intervention. Timeframe calculation includes 6 months (9 cycles of dostarlimab, with each cycle lasting 21 days) plus an additional 12 months of assessment time, amounting to a total of 18 months.

Secondary Outcome Measures
NameTimeMethod
Number of Participants with Sustained Complete Clinical Response for 24 Months (cCR24) as assessed by ICR30 months

cCR24 is achieved when a participant maintains cCR as assessed by ICR for 24 months following their first disease assessment after last dose of study intervention. Timeframe calculation includes 6 months (9 cycles of dostarlimab, with each cycle lasting 21 days) plus an additional 24 months of assessment time, amounting to a total of 30 months.

Number of Participants with Sustained Complete Clinical Response for 36 Months (cCR36) as assessed by ICR42 months

cCR36 is achieved when a participant maintains cCR as assessed by ICR for 36 months following first disease assessment after last dose of study intervention. Timeframe calculation includes 6 months (9 cycles of dostarlimab, with each cycle lasting 21 days) plus an additional 36 months of assessment time, amounting to a total of 42 months.

Number of Participants with Event Free Survival at 3 years (EFS3) as assessed by Investigator3 years

EFS3 is defined as participants who remained alive and free of disease progression precluding surgery, local recurrence, and distant recurrence at 3 years from the first dose of study intervention as assessed by Investigator.

Event Free Survival (EFS) as assessed by InvestigatorUp to approximately 77 months

EFS is defined as time from the date of first dose of study intervention to any of the following events including progression of disease that precludes surgery, local recurrence, distant recurrence (all as assessed by the investigator), or death due to any cause.

Number of Participants with cCR12 as assessed by Investigator18 Months

cCR12 is achieved when a participant maintains cCR as assessed by Investigator for 12 months from the first disease assessment after last dose of study intervention. Timeframe calculation includes 6 months (9 cycles of dostarlimab, with each cycle lasting 21 days) plus an additional 12 months of assessment time, amounting to a total of 18 months.

Number of Participants with cCR24 as assessed by Investigator30 Months

cCR24 is achieved when a participant maintains cCR as assessed by Investigator for 24 months from the first disease assessment after last dose of study intervention. Timeframe calculation includes includes 6 months (9 cycles of dostarlimab, with each cycle lasting 21 days) plus an additional 24 months of assessment time, amounting to a total of 30 months.

Number of Participants with cCR36 as assessed by Investigator42 Months

cCR36 is achieved when a participant maintains cCR as assessed by Investigator for 36 months from the first disease assessment after last dose of study intervention. Timeframe calculation includes 6 months (9 cycles of dostarlimab, with each cycle lasting 21 days) plus an additional 36 months of assessment time, amounting to a total of 42 months.

Objective Response Rate (ORR) assessed by ICRUp to 37 Weeks

ORR is defined as number of participants achieving a partial response (PR), near complete response (nCR) or cCR at post-intervention disease assessment (PIDA) or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or incomplete clinical response (iCR) (PIDA 2) as assessed by ICR.

Objective Response Rate (ORR) as assessed by InvestigatorUp to 37 Weeks

ORR by Investigator is defined as number of participants achieving a PR, nCR, or cCR at PIDA.

Organ Preservation RateUp to 3 years

Organ Preservation Rate is defined as number of participants who did not undergo any rectal cancer surgery either as primary management or for local recurrence, or who did not have a permanent colostomy created, at any time up to 3 years.

Disease-Specific Survival (DSS)Up to approximately 77 months

DSS is defined as time from the date of first dose of study intervention to death due to disease under study.

Disease-Specific Response at 5 years (DSS5)Up to 5 years

DSS5 is defined as the number of participants not dying due to disease under study at 5 years from the first dose of study intervention.

Overall Survival (OS)Up to approximately 77 months

OS is defined as time from first dose of study intervention to death from any cause.

Overall Survival at 5 years (OS5)Up to 5 years

OS5 is defined as number of participants being alive at 5 years from first dose of study intervention.

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.Up to approximately 77 months
Serum concentration of DostarlimabUp to approximately 77 months
Concentration at the end of infusion (C-EOI) of DostarlimabUp to approximately 77 months
Trough Concentration (C-trough) of DostarlimabUp to approximately 77 months
Number of Participants with Anti-Drug Antibodies (ADA) against DostarlimabUp to approximately 77 months

Trial Locations

Locations (1)

GSK Investigational Site

🇨🇳

Taiyuan, China

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