NIMBLE-CRC: NeoImmunoModulation Before Leveraging Excision in Colorectal Rectal Cancer (NCT07677579) | Clinical Trial Compass
Not Yet RecruitingPhase 2
NIMBLE-CRC: NeoImmunoModulation Before Leveraging Excision in Colorectal Rectal Cancer
26 participantsStarted 2026-08-30
Plain-language 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.
Who can participate
Age range
18 Years – 80 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. A signed informed consent must be obtained prior to conducting any study-specific procedures.
* Male or female adult 18 to 80 years of age on day of signing informed consent.
* Histological-confirmed adenocarcinoma of the colon that is amenable to curative intent resection.
* Only participants with pMMR/MSS CRC are eligible. Microsatellite status should be performed per local standard of practice. (e.g., IHC and/or PCR, next-generation sequencing). Subjects with unknown or indeterminate results for either test at the time of enrollment are not eligible.
* Adequate organ and marrow function as defined below:
* Absolute neutrophil count: ≥ 1,500/mcl
* Platelets: ≥ 100,000/mcL without transfusion within 2 weeks of screening laboratory sample collection
* Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). This may be up to 3x ULN if Gilbert's syndrome is documented.
* AST and ALT ≤ 3 x institutional ULN.
* Serum creatinine ≤ 1.5 x ULN and EGFR ≥ 40
* ECOG performance status (PS) 0 or 1.
* Urine protein-to-creatinine ratio ≤ 1mg/mg creatinine.
* INR ≤ 1.5 and aPTT ≤ 1.2 x ULN
* Measurable disease as determined by RECIST v1.1.
* Sexually active fertile subjects and their partners must agree to use highly effective method of contraception during the course of the study and for the follo…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Intent for Curative Surgery Post-Treatment
Timeframe: Within 14-35 days after completion of two cycles of neoadjuvant therapy