A Trial of Regorafenib Plus Lorigerlimab as Neoadjuvant Therapy for Patients With pMMR/MSS, Resectable, Lung-limited Metastatic Colorectal Cancer

NCT07137390 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-0412NCI-2025-06043
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To apply its findings as rationale needed for a subsequent registration trial towards a novel indication for systemic treatment of resectable, lung-limited metastatic CRC.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Treatment with Regorafenib PO + Lorigerlimab IV Q4W

EXPERIMENTAL

Drug: Regorafenib; Drug: Lorigerlimab

Interventions

Regorafenib DRUG

Given Orally

Treatment with Regorafenib PO + Lorigerlimab IV Q4W

Lorigerlimab DRUG

Given Orally

Treatment with Regorafenib PO + Lorigerlimab IV Q4W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age .18 years at the time of informed consent.
• Histologically or cytologically confirmed adenocarcinoma of colon or rectum.
• MSS or pMMR status as tested according to institutional standard practice. For example, pMMR status can be determined by intact expression by immunohistochemistry of all 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) while microsatellite instability can be determined by polymerase chain reaction (PCR) or next generation sequencing (NGS). Note: methodologies (e.g., ddPCR, NGS) to determine microsatellite instability on ctDNA are acceptable for study eligibility evaluation.
• Lung-limited metastatic disease (i.e., no other secondary organ involvement outside of the lung) as determined by the treating provider or PI.
• Note: lesions previously treated with loco-regional approaches (e.g., radiotherapy) with clinical or radiological evidence of progression at the time of study enrolment will be considered evaluable.
• Willing to undergo pretreatment biopsy of a lung metastasis that can be both safely and effectively biopsied at the discretion of the interventional radiology team.
• Identification of the subject as a medically appropriate candidate for surgical resection of the lung metastasis (or metastases) with or without the primary tumor according to the surgeon(s), and the ability to tolerate surgical resection with acceptable operative risk as deemed by surgeon(s) based on performance status and medical comorbidities.
• Resection/definitive therapy of primary colorectal tumor prior to study enrolment with no suspicion of recurrence or planned combined resection with lung metastasis (or metastases) at the discretion of the surgeon(s). Prior radiation to a rectal adenocarcinoma is permitted. Patients who have a complete response to neoadjuvant therapy (e.g., following treatment for localized rectal adenocarcinoma) are eligible at the discretion of the treating provider or PI .
• ECOG Performance Status (PS) of 0 or 1 (APPENDIX A).
• At least one measurable lesion for the lung metastatic disease according to RECIST 1.1 criteria (Section 8.2). Note: lesions measuring \< 10 mm by imaging following tissue collection through screening biopsy may be considered evaluable at their longest diameter in the absence of a viable alternative at the discretion of the treating provider or PI based upon documentation of a clinically determined metastasis.
• Adequate organ and bone marrow function within 28 days prior to registration as defined below:
• absolute neutrophil count . 1.0 \~ 103/uL.
• hemoglobin . 9 g/dL.
• platelet count . 75 \~ 103/uL.
• total bilirubin . 1.5 \~ institutional upper limit of normal (ULN).

You may not qualify if:

• Concomitant extrapulmonary metastatic cancer at the time of study screening . A history of extrapulmonary metastases is permitted only if the participant has undergone definitive treatment (e.g., resection, radiation, ablation etc.) and remains without evidence of disease recurrence and/or progression within 6 months of study registration.
• Systemic anti-cancer treatment within 14 days or less than 5 half-lives (whichever is shorter) of the first dose of study treatment.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Prior treatment with regorafenib or fruquintinib.
• Non-palliative radiotherapy \< 12 weeks before the first dose of study treatment.
• Treatment with any investigational drug within 30 days prior to enrollment or 5 investigational agent half-lives (whichever is longer).
• An active condition requiring systemic treatment with either corticosteroids (\> 10 mg prednisone or equivalents) or other immunosuppressive medications within 14 days of registration. Participants are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Replacement steroid autoimmune disease. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayedtype hypersensitivity reaction caused by a contact allergen) is permitted.
• Impairment of gastrointestinal function or disease, at the discretion of the treating provider or PI that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).
• A history of GI perforation (note: tumor-related perforation of a resected primary tumor is not applicable), GI bleeding within 4 weeks prior to study registration, or clinically significant diverticulitis or flare-up within 4 weeks prior to study registration).
• A history of inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis).
• Note: participants with Graves' disease that is controlled on thyroid supplement/replacement, type 1 insulin-dependent diabetes mellitus that is controlled on insulin therapy, or any other autoimmune disease that is controlled at the discretion of the treating provider or PI while on steroid replacement therapy are allowed to participate.
• A history of pneumonitis that has required oral or IV steroids within the last 12 months.
• A history of a Grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy.
• A history of a prior allogeneic tissue or solid organ transplant.
• A history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) within 6 months prior to study registration.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Van Morris, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 22, 2025
• Study Start: September 3, 2025
• Primary Completion: January 22, 2026
• Study Completion: January 22, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03