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

Phase 2Active Not RecruitingNCT06640049

GlaxoSmithKline23 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms, Rectal

Interventions

DostarlimabBIOLOGICAL

Dostarlimab will be administered.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (9)

GSK Investigational Site

Chengdu, China

GSK Investigational Site

Chongqing, China

GSK Investigational Site

Guangzhou, China

GSK Investigational Site

Guangzhou, China

Outcomes

Primary Outcomes

Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR)

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.

Time frame: 18 months

Secondary Outcomes

Number of Participants with Sustained Complete Clinical Response for 24 Months (cCR24) as assessed by ICR

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.

Time frame: 30 months

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

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.

Time frame: 42 months

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

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.

Time frame: 3 years

Data from ClinicalTrials.gov

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GSK Investigational Site

Hangzhou, China

GSK Investigational Site

Hangzhou, China

GSK Investigational Site

Jinan, China

GSK Investigational Site

Kunming, China

GSK Investigational Site

Shanghai, China

Event Free Survival (EFS) as assessed by Investigator

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.

Time frame: Up to approximately 77 months

Number of Participants with cCR12 as assessed by Investigator

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.

Time frame: 18 Months

Number of Participants with cCR24 as assessed by Investigator

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.

Time frame: 30 Months

Number of Participants with cCR36 as assessed by Investigator

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.

Time frame: 42 Months

Objective Response Rate (ORR) assessed by ICR

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.

Time frame: Up to 37 Weeks

Objective Response Rate (ORR) as assessed by Investigator

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

Time frame: Up to 37 Weeks

Organ Preservation Rate

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.

Time frame: Up to 3 years

Disease-Specific Survival (DSS)

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

Time frame: Up to approximately 77 months

Disease-Specific Response at 5 years (DSS5)

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.

Time frame: Up to 5 years

Overall Survival (OS)

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

Time frame: Up to approximately 77 months

Overall Survival at 5 years (OS5)

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

Time frame: Up to 5 years

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.

Time frame: Up to approximately 77 months

Serum concentration of Dostarlimab

Time frame: Up to approximately 77 months

Concentration at the end of infusion (C-EOI) of Dostarlimab

Time frame: Up to approximately 77 months

Trough Concentration (C-trough) of Dostarlimab

Time frame: Up to approximately 77 months

Number of Participants with Anti-Drug Antibodies (ADA) against Dostarlimab

Time frame: Up to approximately 77 months