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

Overview

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.

Interventions

• Biological Dostarlimab
  Dostarlimab will be administered.
• Drug CAPEOX
  CAPEOX chemotherapy consisting of capecitabine and oxaliplatin will be administered.

Primary outcome measures

• Major pathological response (mPR) rate [Time frame: Up to approximately 18 weeks]
• 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 [Time frame: Up to approximately 105 weeks]

Secondary outcome measures (5)

• Percentage of participants for whom primary tumour resection is not excluded [Time frame: Up to approximately 18 weeks]
• Complete pathologic response (cPR) rate [Time frame: Up to approximately 18 weeks]
• Major pathological response excluding cPR rate [Time frame: Up to approximately 18 weeks]
• Partial pathologic response rate [Time frame: Up to approximately 18 weeks]
• Negligible pathologic response rate [Time frame: Up to approximately 18 weeks]

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-

• 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
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Belgium · 11 centers

• GSK Investigational Site — Aalst
• GSK Investigational Site — Bonheiden
• GSK Investigational Site — Brussels
• GSK Investigational Site — Brussels
• GSK Investigational Site — Ghent
• GSK Investigational Site — Leuven
• GSK Investigational Site — Liège
• GSK Investigational Site — Liège
• … and 3 more centers

Spain · 9 centers

• GSK Investigational Site — Barcelona
• GSK Investigational Site — Barcelona
• GSK Investigational Site — Barcelona
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Oviedo
• … and 1 more center

Japan · 4 centers

• GSK Investigational Site — Osaka
• GSK Investigational Site — Osaka
• GSK Investigational Site — Tokyo
• GSK Investigational Site — Tokyo

United Kingdom · 4 centers

• GSK Investigational Site — Glasgow
• GSK Investigational Site — Leeds West Yorkshire
• GSK Investigational Site — London
• GSK Investigational Site — Sutton

Italy · 3 centers

• GSK Investigational Site — Milan
• GSK Investigational Site — Roma
• GSK Investigational Site — Udine

Switzerland · 2 centers

• GSK Investigational Site — Bern
• GSK Investigational Site — Geneva

Identifiers

NCT: NCT06567782 · 222892 · 2024-513441-36

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗