XELOX Plus DoSTARlimab Versus XELOX Alone as Consolidation Treatment After Standard Chemoradiation in pMMR/MSS or MSI-Low Locally Advanced Rectal Cancer (LARC) Patients (IMMUNOSTAR)

January 26, 2026 updated by: Gruppo Oncologico Italiano di Ricerca Clinica

Phase II Randomized Trial of XELOX Plus DoSTARlimab Versus XELOX Alone as Consolidation Treatment After Standard Chemoradiation in pMMR/MSS or MSI-Low Locally Advanced Rectal Cancer (LARC) Patients - IMMUNOSTAR Trial GOIRC-02-2024

This is a phase II, multicenter, randomized (2:1) controlled, clinical trial to evaluate the preliminary efficacy and safety of consolidation chemotherapy (XELOX) plus dostarlimab after standard long-course CRT (ARM A) compared to XELOX alone (ARM B) in patients with pMMR/MSS or MSI-Low LARC (cT3-4 cN0, any cT cN+) candidate to receive standard long course CRT followed by TME. After the surgery, the patients in ARM A will be randomized (1:1) to receive adjuvant dostarlimab (ARM A1) versus follow-up (ARM A2), and in ARM B only follow-up.

If clinical complete responses (cCR) are documented after consolidation treatment, the patient may choose not to proceed with surgery and pursue nonoperative management (NOM).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase II, multicenter, randomized (2:1) controlled, clinical trial to evaluate the preliminary efficacy and safety of consolidation chemotherapy (XELOX) plus anti-PD-1 antibody (dostarlimab) after standard long-course CRT followed by adjuvant dostarlimab versus follow-up (ARM A) compared to XELOX alone as consolidation (ARM B) in patients with pMMR/MSS or MSI-Low LARC (cT3-4 cN0, any cT cN+) candidate to receive standard long course CRT followed by TME.

Subsequent randomization into a ratio 1:1 will be performed after surgery, only for patients randomized in ARM A, to receive adjuvant dostarlimab for a maximum of 8 cycles (ARM A1) versus only follow-up (ARM A2), and in ARM B only follow-up (Figure 1).

If clinical complete responses (cCR) are documented after restaging, the patient may choose not to proceed with surgery and pursue nonoperative management (NOM) (Figure 1).

The patients before randomization will be stratified as follows:

  • cT4 or < cT4 stage;
  • positive or negative lymph nodes.

Study Type

Interventional

Enrollment (Estimated)

270

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Arezzo, Italy
        • Ospedale San Donato - UOC Oncologia Medica dell'Aretino, Casentino, Valtiberina, Valdichiana Aretina
        • Contact:
        • Principal Investigator:
          • Carlo Milandri
      • Aviano, Italy
        • Oncologia medica e prevenzione oncologica - Centro di Riferimento Oncologico
        • Contact:
        • Principal Investigator:
          • Michela Guardascione
      • Bologna, Italy
        • UOC Oncologia Medica IRCCS Azienda Ospedaliero-Universitaria di Bologna
        • Contact:
        • Principal Investigator:
          • Fabiola Lorena Rojas
      • Brescia, Italy
        • Oncologia Medica Fondazione Poliambulanza Istituto Ospedaliero
        • Contact:
        • Principal Investigator:
          • Michela Lambertini
      • Catania, Italy
        • UOC Oncologia Medica - ARNAS Garibaldi PO Nesima
        • Principal Investigator:
          • Roberto Bordonaro
        • Contact:
      • Cuneo, Italy
        • A.O. Oncologia S. Croce e Carle - presidio Ospedaliero A. Carle
        • Contact:
        • Principal Investigator:
          • Elena Fea
      • Florence, Italy
        • AOUC Azienda Ospedaliero - Universitaria Careggi Oncologia Medica
        • Principal Investigator:
          • Lorenzo Antonuzzo
        • Contact:
      • Genova, Italy
        • U.O. Oncologia Medica 1 IRCCS Ospedale Policlinico San Martino
        • Principal Investigator:
          • Alessandro Pastorino
        • Contact:
      • La Spezia, Italy
        • S.C. Oncologia Medica, Ospedale Felettino
        • Contact:
        • Principal Investigator:
          • Carlo Aschele
      • Meldola (FC), Italy
        • IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
        • Contact:
        • Principal Investigator:
          • Francesco Giulio Sullo
      • Milan, Italy
        • Oncologia Falck - ASST Grande Ospedale Metropolitano Niguarda
        • Principal Investigator:
          • Salvatore Siena
        • Contact:
      • Milan, Italy
        • Struttura Complessa Oncologia Medica 1 - Fondazione IRCCS Istituto Nazionale dei Tumori
        • Principal Investigator:
          • Filippo Pietrantonio
        • Contact:
      • Modena, Italy
        • AOU di Modena - Policlinico di Modena - DH Oncologico
        • Contact:
        • Principal Investigator:
          • Fabio Gelsomino
      • Napoli, Italy
        • UOC Oncoematologia AOU Vanvitelli
        • Principal Investigator:
          • Erika Martinelli
        • Contact:
      • Napoli, Italy
        • Oncologia Clinica Sperimentale Addome Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale
        • Principal Investigator:
          • Antonio Avallone
        • Contact:
      • Napoli, Italy
        • UOC Di Oncologia Medica AOU Federico II
        • Contact:
        • Principal Investigator:
          • Chiara Carlomagno
      • Padua, Italy
        • UOC Oncologia 1 - Ospedale Busonera - IRCCS Istituto Oncologico Veneto
        • Principal Investigator:
          • Francesca Bergamo
        • Contact:
      • Parma, Italy
        • UOC Oncologia Medica Azienda Ospedaliero Universitaria di Parma
        • Contact:
        • Principal Investigator:
          • Francesca Pucci
      • Pavia, Italy
        • SC Oncologia, Fondazione IRCCS Policlinico S. Matteo
        • Principal Investigator:
          • Anna Pagani
        • Contact:
      • Pisa, Italy
        • Oncologia Medica 2 Universitaria
        • Principal Investigator:
          • Gianluca Masi
        • Contact:
      • Ravenna, Italy
        • UOC Oncologia Ravenna Dipartimento di Oncologia ed Ematologia - AUSL Romagna
        • Principal Investigator:
          • Stefano Tamberi
        • Contact:
      • Reggio Emilia, Italy
        • SOC di Oncologia Provinciale, AUSL IRCCS di Reggio Emilia
        • Principal Investigator:
          • Maria Banzi
        • Contact:
      • Roma, Italy
        • Fondazione Policlinico Universitario Campus Bio-Medico
        • Principal Investigator:
          • Giuseppe Tonini
        • Contact:
      • Roma, Italy
        • Oncologia Medica - Policlinico Universitario Gemelli IRCCS
        • Principal Investigator:
          • Lisa Salvatore
        • Contact:
      • Rozzano, Italy
        • IRCCS Istituto Clinico Humanitas
        • Contact:
        • Principal Investigator:
          • Alberto Puccini
      • San Giovanni Rotondo, Italy
        • Oncologia Ricerca Clinica - IRCCS Casa Sollievo della Sofferenza
        • Contact:
        • Principal Investigator:
          • Tiziana Latiano
      • Sassari, Italy
        • U.O. C. di Oncologia Medica - OSPEDALE CIVILE SS ANNUNZIATA
        • Contact:
        • Principal Investigator:
          • Alessio Cogoni
      • Torino, Italy
        • Oncologia Medica 1, A.O.U. Città della Salute e della Scienza di Torino Ospedale Molinette
        • Principal Investigator:
          • Massimo Di Maio
        • Contact:
      • Udine, Italy
        • SOC Oncologia Azienda sanitaria Universitaria Friuli Centrale - P.O. S. Maria della Misericordia
        • Contact:
        • Principal Investigator:
          • Valentina Fanotto
      • Vimercate, Italy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically proven rectal adenocarcinoma with distal extension less 16 cm from the anal verge.
  • Stage cT3-4 cN0 cM0, any cT cN+ M0 [N+ stage, three or more lymph nodes of diameter >0.5 cm measured by endorectal ultrasound, or one or more lymph nodes of diameter >1 cm measured by magnetic resonance (MRI)].
  • Proficient mismatch repair (pMMR)/microsatellite stable status (MSS) or microsatellite instability (MSI)-low (MSI-L)
  • ECOG-Performance Status 0-1
  • No previous treatment with chemotherapy or radiation therapy.
  • No prior exposure to immune-mediated therapy, excluding therapeutic anticancer vaccines.
  • Neutrophil count >1,500/mL, platelet count >100.000/mL, hemoglobin >9.0 g/dL, serum creatinine <1.5 3 upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase 2.5 3 ULN, total bilirubin <1.5 3 ULN.
  • Signed written informed consent.

Exclusion Criteria:

  • Subjects with active, known, or suspected autoimmune disease requiring systemic treatment (systemic steroids or immunosuppressive agents), except for subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune conditions only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Distant metastases documented.
  • Participants have received a live vaccine within 30 days of the planned start of study therapy. COVID-19 vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.
  • Participants have a current active history of pneumonitis or interstitial lung disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XELOX + DOSTARLIMAB (Arm A)
4 cycle - consolidation chemotherapy (XELOX) plus anti-PD-1 antibody (dostarlimab) after standard long-course CRT, followed by randomisation to adjuvant dostarlimab (Arm A1) versus follow-up (Arm A2)
Drug: XELOX (Capecitabine and Oxaliplatin)
Capecitabine 1000mg/m2 BID + Oxaliplatin 130mg/m2 Q3W
Drug: Dostarlimab
Dostarlimab IV 500mg Q3W
Active Comparator: XELOX (Arm B)
4 cycle- XELOX alone as consolidation treatment
Drug: XELOX (Capecitabine and Oxaliplatin)
Capecitabine 1000mg/m2 BID + Oxaliplatin 130mg/m2 Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical complete response (cCR) at 12 months
Time Frame: After 12 months of the end of the consolidation therapy
To evaluate the clinical complete response (cCR) after 12 months of the end of consolidation treatment, defined as an absence of residual disease on digital and endoscopic rectal examination, as well as the absence of residual disease on rectal MRI, with no restricted diffusion on T2-weighted imaging (cT0N0M0), or the pathological complete response (pCR), in patients who undergo surgery, defined as an absence of viable tumor cells after full pathologic examination of the resected specimen (pT0N0M0)
After 12 months of the end of the consolidation therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical complete response (cCR) at 24 and 36 months
Time Frame: After 24 and 36 months of the end of the consolidation therapy
To evaluate cCR at 24 and 36 months defined as an absence of residual disease on digital and endoscopic rectal examination, as well as the absence of residual disease on rectal MRI, with no restricted diffusion on T2-weighted imaging
After 24 and 36 months of the end of the consolidation therapy
Assessment of Organ Preservation Rate
Time Frame: From the enrollmentat to any time up to 3 years
To assess Organ Preservation Rate defined as not undergoing Total Mesorectal Excision (TME), either as primary management or for local recurrence, or who did not have a permanent colostomy created, at any time up to 3 years.
From the enrollmentat to any time up to 3 years
Disease Free Survival
Time Frame: From randomization to recurrence of a tumor up to 3 years
To evaluate DFS
From randomization to recurrence of a tumor up to 3 years
Overall Survival
Time Frame: From initiation of study treatment to death from any cause up to 3 years
To evaluate OS
From initiation of study treatment to death from any cause up to 3 years
Pathological Downstaging Rate
Time Frame: Perioperative period (at surgical resection).
Pathological downstaging defined as a reduction in tumor stage comparing post-surgical pathological TNM stage (ypTNM) with baseline clinical TNM stage (cTNM).
Perioperative period (at surgical resection).
Improvement of Quality of Life
Time Frame: Baseline, during treatment, and at the end of adjuvant therapy (approximately 12 months).
To assess the QoL measured as pre-defined PRO endpoints in this study are mean changes from baseline in the EORTC-QLQ-CR29 questionnaire administered at baseline, after chemoradiation, after consolidation therapy, before to start adjuvant therapy and at the end of adjuvant therapy
Baseline, during treatment, and at the end of adjuvant therapy (approximately 12 months).
Adverse Events
Time Frame: From first dose of study treatment through study completion, an average of 3 years
To evaluate safety in terms of incidence, nature, frequency and severity of Adverse Events (AEs) and laboratory abnormalities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.
From first dose of study treatment through study completion, an average of 3 years
Association Between ctDNA Status and Clinical Outcomes
Time Frame: From ctDNA assessment during treatment through follow-up, up to 3 years.
ctDNA status (positive vs negative) assessed at predefined time points and its association with clinical outcomes, including disease recurrence and treatment decisions.
From ctDNA assessment during treatment through follow-up, up to 3 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Oncologico Italiano di Ricerca Clinica

Collaborators

GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 31, 2026

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

March 28, 2025

First Submitted That Met QC Criteria

January 26, 2026

First Posted (Actual)

February 2, 2026

Study Record Updates

Last Update Posted (Actual)

February 2, 2026

Last Update Submitted That Met QC Criteria

January 26, 2026

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GOIRC-02-2024

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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