A Trial of Regorafenib Plus Lorigerlimab in Patients With Locally Recurrent or Regrowing pMMR/MSS Localized Rectal Cancer

NCT07223567 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0809NCI-2025-08120
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective single-center, single-arm, open-label, phase II study evaluating the safety, activity, and efficacy of regorafenib in combination with lorigerlimab for the treatment of patients with regrowing or locally recurrent pMMR/MSS localized rectal cancer following TNT.

Conditions

Rectal Cancer; Rectal Cancer Recurrent

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

Participants will be treated with the combination of regorafenib 90mg PO daily on D1-21 Q28 days and lorigerlimab 6mg/kg IV Q28 days for 3 months.

Drug: Regorafenib; Drug: Lorigerlimab

Interventions

Regorafenib DRUG

Given by mouth

Also known as: Stivarga

Treatment with Regorafenib PO + Lorigerlimab IV Q4W

Lorigerlimab DRUG

Give by IV infusion

Also known as: MGD019

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:

• Histological or pathological confirmation of rectal or anal adenocarcinoma (collectively referred to as "rectal cancer" or "rectal (adeno)carcinoma" throughout this protocol).
• 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.
• The evidence of regrowth, confirmed by biopsy, following a near-complete or complete response at least three months following completion of planned total neoadjuvant therapy or locally recurrent disease after total neoadjuvant therapy as treatment for localized rectal cancer at the discretion of the treating provider or PI.
• The potential for R0 (complete) resection of the residual cancer at the discretion of the surgeon must be documented.
• Willing to undergo pretreatment biopsy of the regrowing or recurrent rectal cancer that can be both safely and effectively biopsied at the discretion of the collaborator.
• ECOG performance status of 0 or 1 (APPENDIX A).
• Ability to understand, willingness to sign a written informed consent document and compliance with the study procedures.
• Ability to swallow and retain pills.
• Adequate organ and marrow function within 28 days prior to registration as defined below:
• absolute neutrophil count . 1.0 x 103/uL
• hemoglobin . 9 g/dL
• platelet count . 75 x 103/uL
• total bilirubin . 1.5 x institutional upper limit of normal (ULN)
• AST/ALT . 3 \~ institutional ULN.

You may not qualify if:

• The presence of distant metastatic disease at the time of study screening, or a history of any distant metastatic colorectal cancer.
• Re-irradiation (a second course of definitive radiation) as definitive therapy for locally recurrent disease after previous standard therapy for localized rectal cancer.
• 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.
• Planned treatment with other systemic anti-cancer agents (e.g., chemotherapy, hormonal therapy, immunotherapy) or other treatments not part of protocolspecified anti-cancer therapy including concurrent investigational agents of any type.
• Prior treatment with regorafenib or fruquintinib.
• 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 daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Participants are permitted the use of topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Replacement steroid doses \> 10 mg daily prednisone or equivalents are permitted in the absence of active 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., delayed-type 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.
• A history of myocarditis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator
• MacroGenics: collaborator

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Alisha H Bent, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2025
• First Posted: November 3, 2025
• Study Start: October 27, 2025
• Primary Completion: January 22, 2026
• Study Completion: January 22, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02