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NIMBLE-CRC: NeoImmunoModulation Before Leveraging Excision in Colorectal Rectal Cancer

NCT07677579 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 26

Last updated 2026-07-01

No results posted yet for this study

Summary

This is a Phase II, single-arm, open-label trial evaluating the feasibility, safety, and preliminary activity of neoadjuvant Zanzalintinib (a VEGFR-targeting TKI) and Retifanlimab (an anti-PD-1 antibody) in patients with resectable stage II-III mismatch repair-proficient (pMMR) colon cancer. The study's primary objective is to determine the proportion of patients able to undergo curative-intent surgery within 14-35 days after completing two cycles (6 weeks) of neoadjuvant therapy. Secondary objectives include assessment of safety/tolerability and rates of pathologic response, including tumor regression grade (TRG). Two-year relapse-free survival (RFS) will also be evaluated.

This trial builds on emerging evidence from neoadjuvant immunotherapy studies-including in pMMR tumors-and the recently positive readout of STELLAR-303, which evaluated Zanzalintinib plus a PD-(L)1 inhibitor in refractory metastatic colorectal cancer. With a favorable safety profile, short treatment window, and rapid post-treatment pathologic readout, this study provides a low-risk opportunity to test whether immunotherapy-based neoadjuvant strategies can improve outcomes and potentially redefine management in early-stage, pMMR colon cancer.

Conditions

  • Colon Cancer Metastatic

Interventions

DRUG

Retifanlimab

Retifanlimab-dlwr is a programmed death receptor-1 (PD-1)-blocking antibody. Retifanlimab-dlwr is a humanized IgG4 kappa monoclonal antibody produced in Chinese hamster ovary cells. Retifanlimab-dlwr has an approximate molecular weight of 148 kDa. ZYNYZ (retifanlimab-dlwr) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution for intravenous use. The solution is free from visible particles. Each single-dose vial contains 500 mg of retifanlimab-dlwr in 20 mL of solution. Each mL contains 25 mg of retifanlimab-dlwr, glacial acetic acid (0.18 mg), polysorbate 80 (0.1 mg), sodium acetate (0.57 mg), sucrose (90 mg), and Water for Injection, USP. The pH is 5.1

DRUG

Zanzalintinib

Chemical Name: N-(4-fluorophenyl)-N-(4-((7-methoxy-6-(methylcarbamoyl)quinoline-4-yl)oxy)phenyl)cyclopropane-1,1-dicarboxamide hemi-fumarate. Zanzalintinib doses administered reflect salt weight-converted free base equivalent (FBE) doses. Exelixis will provide each Investigator with adequate supplies of zanzalintinib, which will be supplied as 60mg, 40 mg or 20mg film-coated tablets. Tablets should be stored at room temperature.

Sponsors & Collaborators

  • Northwell Health

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-08-30
Primary Completion
2028-08-30
Completion
2028-12-30
FDA Drug
Yes

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Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07677579 on ClinicalTrials.gov