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)

Gruppo Oncologico Italiano di Ricerca Clinica

Status and phase: Not yet enrolling; Phase 2

Conditions: Locally Advanced Rectal Cancer (LARC)

Treatments: Drug: XELOX (Capecitabine and Oxaliplatin); Drug: Dostarlimab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07381777

GOIRC-02-2024

Details and patient eligibility

About

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).

Full 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.

Enrollment: 270 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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270 participants in 2 patient groups

XELOX + DOSTARLIMAB (Arm A)

Experimental group

Description:

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)

Treatment:

Drug: Dostarlimab

Drug: XELOX (Capecitabine and Oxaliplatin)

XELOX (Arm B)

Active Comparator group

Description:

4 cycle- XELOX alone as consolidation treatment

Treatment:

Drug: XELOX (Capecitabine and Oxaliplatin)