Clinical trial NCT06567782: A Study of Neoadjuvant Dostarlimab Plus Capecitabine Plus Oxaliplatin (CAPEOX) Vs CAPEOX With Previously Untreated T4N0 or Stage III Mismatch Repair Proficient (MMRp)/Microsatellite Stable (MSS) Colon Cancer
Official title: A Phase 2, Open Label, Randomized Study of Neoadjuvant Dostarlimab Plus CAPEOX Versus CAPEOX in Participants With Previously Untreated T4N0 or Stage III MMRp/ MSS Colon Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neoplasms, Colon
Keywords: Colon cancer
MMRp
MSS
Dostarlimab
CAPEOX
Neoadjuvant
GSK4057190A
TSR-042
Chemotherapy
Immunotherapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-08-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main goal of this study is to test a new treatment approach for colon cancer. The treatment involves dostarlimab along with a specific type of chemotherapy called CAPEOX (short for "capecitabine + oxaliplatin") to check if using these two together works better than using just CAPEOX by itself. This treatment is given before any surgery takes place; a method referred to as "neoadjuvant therapy." . The aim is to see if this new approach can show early signs of effectiveness in treating participants with a specific type of colon cancer known as mismatch repair proficient/ microsatellite stable (MMRp/MSS), where the cells have normal repair systems and stable DNA sequences. This study will also look at specific signs in the blood and tumor to see if they can help predict how well the treatment is working. This could help better understand how dostarlimab contributes to the response of the disease to treatment.


Eligibility criteria: Inclusion Criteria:

* Has untreated pathologically confirmed colon adenocarcinoma
* Has resectable colon adenocarcinoma defined as clinically T4N0 or Stage III
* Has a tumor demonstrating the presence of either-

  1. MMR status: MMR status must be assessed by Immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where all proteins are present indicates MMRp; MMR status may be determined local laboratory; or
  2. MSS or Microsatellite Instability-L (MSI-L) phenotype as determined by polymerase chain reaction (PCR) or by tissue next generation sequencing (NGS), determined by local laboratory
* Provides fresh tumor tissue obtained during either the pre-screening or screening period via colonoscopy performed per procedure manual. Tissue biopsy is required
* Is willing to use adequate contraception male and/or female participants
* Has an Eastern Cooperative Oncology Group - Performance status (ECOG-PS) of 0 or 1
* Has adequate organ function

Exclusion Criteria:

* Has distant metastatic disease
* Has received prior medical therapy (chemotherapy, immunotherapy, biologic, or targeted therapy), radiation therapy or surgery for management of colon cancer
* Has, in the investigator's opinion, a tumor that is not amenable to surgery or has any other contraindication to surgery
* Has experienced any of the following with prior immunotherapy: any imAE ≥ Grade 3, immune-mediated severe neurologic events of any-grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade \[Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), or Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome\], or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary
* Has any history of interstitial lung disease or immune-related pneumonitis
* Has a history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the study results, interfere with their 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
* Is considered, in investigator's opinion, a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection requiring systemic therapy
* Has received treatment with an investigational agent within \[4 weeks\] of the first dose of study intervention
* Is pregnant or breastfeeding
* 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, or any components of CAPEOX

Primary outcomes:
measure: Major pathological response (mPR) rate
timeFrame: Up to approximately 18 weeks
measure: Number of participants with adverse events (AEs), serious adverse events (SAEs), immune-mediated adverse events (imAEs), and AEs leading to death or discontinuation of study intervention
timeFrame: Up to approximately 105 weeks
Secondary outcomes:
measure: Percentage of participants for whom primary tumour resection is not excluded
timeFrame: Up to approximately 18 weeks
measure: Complete pathologic response (cPR) rate
timeFrame: Up to approximately 18 weeks
measure: Major pathological response excluding cPR rate
timeFrame: Up to approximately 18 weeks
measure: Partial pathologic response rate
timeFrame: Up to approximately 18 weeks
measure: Negligible pathologic response rate
timeFrame: Up to approximately 18 weeks
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: GSK Investigational Site
city: Bonheiden
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liege
country: Belgium
facility: GSK Investigational Site
city: Oostende
country: Belgium
facility: GSK Investigational Site
city: Roeselare
country: Belgium
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
References: