Real-world Efficacy and Safety of Neoadjuvant Dostarlimab in Patients With dMMR/MSI-H Locally Advanced Rectal Cancer (RW-NEDOS)

This is an observational, retrospective-prospective, multicentre trial enrolling all patients included in the AIFA monitoring registry of Dostarlimab for the indication in rectal cancer. The aims of the study are to describe the clinical outcomes and safety of patients with dMMR/MSI-H locally advanced rectal cancer (LARC) receiving neoadjuvant dostarlimab in the real-world setting.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Cancer (LARC)
• Intervention / Treatment: Drug: Dostarlimab

Detailed Description

The primary objective is to describe the activity of neoadjuvant dostarlimab in terms of objective response rate (RECIST 1.1).

Secondary objectives are:

1. To describe the activity of neoadjuvant dostarlimab in terms of:

   • complete clinical response rate at 6 and 12 months
   • time to clinical complete response
   • duration of clinical complete response
   • near-complete clinical response rate at 6 and 12 months
   • duration of near-complete clinical response
   • duration of objective response
   • rate of surgery (total mesorectal excision or local excision)
   • pathological complete response rate
   • objective response rate (RECIST 1.1) assessed by central radiological review.
2. To describe the safety of neoadjuvant dostarlimab in terms of: Adverse events/SAE incidence and outcome, time and duration of toxicity according to CTCAE v5.0.
3. To descrive the efficacy of neoadjuvant dostarlimab in terms of: event free-survival (EFS), organ preservation at 3 years, time to ditance recurrence and overall survival (OS)

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Maria Carmela Piccirillo, MD; Phone Number: +39 08117770280; Email: m.piccirillo@istitutotumori.na.it
• Study Contact Backup: Name: Piera Gargiulo, MD; Phone Number: +39 081 1777 0279; Email: piera.gargiulo@istitutotumori.na.it

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Not yet recruiting
    • ASL Napoli 1, Presidio Ospedaliero Ospedale del mare, Oncologia medica
    • Principal Investigator: Bruno Daniele, MD
    • Contact: Bruno Daniele, MD; Phone Number: 081 1777 0279; Email: bruno.daniele@aslnapoli1centro.it
  • Napoli, Italy
    • Recruiting
    • IRCCS Fondazione G. Pascale, Unità Operativa Complessa Oncologia Addominale
    • Principal Investigator: Antonio Avallone, MD
    • Contact: Antonio Avallone, MD; Phone Number: +39 081177703557; Email: a.avallone@istitutotumori.na.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients (any sex/gender) with dMMR/MSI-H locally advanced rectal cancer treated with dostarlimab are eligible for this study.

Description

Inclusion Criteria:

• Signed informed consent form
• Age > 18 years
• Histologically confirmed stage II-III rectal cancer
• dMMR/MSI status assessed locally by Immunohistochemistry, next-generation sequencing or PCR

For the retrospective part of the study:

• At least one dose of neoadjuvant dostarlimab from November 2023 (i.e. within the period of AIFA dostarlimab monitoring registry activation for the indication in rectal cancer, which is reimbursed according to the Italian law 648/1996, GU n.252 as of 27/10/2023)
• Eligible deceased or unreachable patients will also be included to avoid selection biases, in respect of the article 110 bis, paragraph 4 of the Italian Privacy Code (a Data Protection Impact Assessment will be produced and published on the Sponsor website before study initiation, and patients explicitly unwilling before death will be not included).

For the prospective part of the study:

- Inclusion in the AIFA dostarlimab monitoring registry for the indication in rectal cancer, to receive dostarlimab according to the Italian law 648/1996, GU n.252 as of 27/10/2023

Exclusion Criteria:

• - Distant metastasis
• Major cognitive dysfunction or psychiatric disorders
• Any previous systemic or local treatment for rectal cancer
• Dostarlimab received within an interventional clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stage II-III rectal cancer (LARC); patients with dMMR/MSI LARC treated with neoadjuvant dostarlimab	Drug: Dostarlimab; Dostarlimab 500 mg iv every 3 weeks for 9 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Defined as the percentage of trial participants having a CR or PR, as per RECIST v1.1.	after 3 , 6 and 9 cycles of dostarlimab. Each cycle is 21 days. Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of clinical complete response	defined as the time from the first documented date of clinical complete response to the date of documented local tumor regrowth, disease recurrence, or last available follow-up, whichever occurs first.	up to to 12 months
near-complete clinical response rate	absence of mass at digital rectal exam, small mucosal irregularity or superficial ulcer no more than 2 cm in diameter at endoscopic exam, and no metastatic nodes at MRI.	at 6 and 12 months up to 12 months
duration of near-complete clinical response	defined as the time from the first documented date of near-complete clinical response to the date of documented conversion to complete clinical response, local tumor regrowth, disease recurrence, or last available follow-up, whichever occurs first.	up to 12 months
rate of surgery (total mesorectal excision or local excision)	defined as the proportion of patients who undergo surgical resection of the primary tumor, including either total mesorectal excision (TME) or local excision	at 6 months (at the end of neoadjuvant dostarlimab)
pathological complete response rate	defined as a Tumor Regression Grade (TRG) 1 according to Mandard modified scoring system.	after surgery (at 6 months)
objective response rate assessed by central radiological review	defined as the percentage of trial participants having a CR or PR, as per RECIST v1.1.	fter 3 , 6 and 9 cycles of dostarlimab. Each cycle is 21 days. Up to 6 months
safety of neoadjuvant dostarlimab	Adverse events/Serious adverse events incidence and grading according to NCI-CTCAE v. 5.0	at the end of each cycle of dostarlimab (every 21 days ) up to 6 months
Event-free survival	defined as the time between dostarlimab starting and disease recurrence (local or distant), or disease progression (radiological or clinical) or second primary colorectal malignancy, or death from any cause, whichever comes first.	up to 12 months
Time to distant recurrence	defined as the time between dostarlimab starting and distant disease recurrence or progression. Patients who do not have a distant recurrence and are alive at the end of the study will be censored at the date of the last assessment visit.	up to 12 months
Overall survival	defined as the time between dostarlimab starting and death from any cause. Patients alive at the end of the study will be censored at the date of the last follow-up contact.	up to 12 months

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples
• Investigators: Principal Investigator: Maria Carmela Piccirillo, MD, National Cancer Institute, IRCCS Fondazione G. Pascale

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Actual): December 8, 2025

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: dostarlimab; real-world; neoadjuvant setting; mismatch repair-deficient LARC; retrospective-prospective study
• Additional Relevant MeSH Terms: dostarlimab
• Other Study ID Numbers: RW-NEDOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No