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Rectal CancerPhase 2NCT07223567

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

A Phase 2 study testing Regorafenib and Lorigerlimab in people with Rectal Cancer and Rectal Cancer Recurrent, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rectal Cancer, Rectal Cancer Recurrent
What is being tested?
Regorafenib and Lorigerlimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
27 Oct 2025to 22 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Serum creatinine . 1.5 ~ the institutional ULN OR measured OR calculated creatinine clearance . 40 mL/min using the following Cockroft-Gault equation as follows: CrCl (mL/min) = [(140 . age) x (weight in kg) € [72 x (serum creatinine in mg/dL)] [0.85 if female].
  • Adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better.
  • The effects of the combination of regorafenib and lorigerlimab on the developing human fetus are unknown. For this reason, some participants (as defined below) must be willing to use contraception (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). Female participants who are not postmenopausal (defined as having no menses for at least one year without an alternative medical cause and confirmed with high follicle-stimulating hormone level), i.e., of childbearing potential, must agree to use a highly effective contraception method (either combined estrogen and progestogen contraception, progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, or bilateral tubal occlusion, or similar). For males, they must have either undergone bilateral orchiectomy, vasectomy with medical confirmation of surgical success, or agree to use male condom if engaging in sexual activity with female of childbearing potential who uses a highly effective contraception method (either combined estrogen and progestogen contraception, progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, or bilateral tubal occlusion, or similar). A double-barrier contraceptive method (male use of condom and female use of cap, diaphragm, or sponge with spermicide) is required while on study (i.e., from time of consent) and through 7 months after last dose of both study drugs for females of childbearing potential. If a female participant has a partner with medical confirmation of surgically successful vasectomy, this can be used in lieu of the aforementioned criteria. For males engaging in sexual activity with a female of childbearing potential, contraception is required while on study (i.e., from time of consent) and through 7 months after last dose of Lorigerlimab, and 4 months after last dose of Regorafenib.

Who cannot join

  • 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).
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  • 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.
  • Persistent proteinuria of NCI-CTCAE Grade 3. Urine dipstick result of 3+ or abnormal, based on type of urine test strip used, is allowed if protein excretion (estimated by urine protein/creatinine ratio on a random urine sample) is <3.5 g/24 hr.
  • History of uncontrolled intercurrent illness including but not limited to:
  • Uncontrolled active infection requiring antibiotics at the time of initiation of study treatment.
  • Uncontrolled cardiac arrythmias.
  • Non-healing wound or non-healing ulcer.
  • Major surgical procedure or significant traumatic injury within 28 days before start of study medication. If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Other co-existing malignancies or previous malignant disease (other than colorectal cancer) within the last 3 years except for thyroid cancer (papillary or follicular), non-melanoma skin cancers, the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, breast, or melanoma and any malignancy deemed in complete remission prior to study entry for which no additional therapy is required or anticipated to be required during the study period.
  • Administration of a live, attenuated vaccine within 120 days prior to start of study treatment or anticipation that such a live attenuated vaccine will be required during the study. Administration of live, attenuated vaccines is therefore prohibited during study treatment. Inactivated vaccines are allowed (for example, inactivated influenza vaccines).
  • Coexisting separate disease, metabolic disorder, clinically significant laboratory result, or any other condition that the treating provider or PI suspects may (a) prohibit use of the investigational product, or (b) put the patient at undue risk of harm.
  • Known active viral hepatitis B (i.e., HBsAg positive prior to enrollment) or hepatitis C infection. Patients with past or resolved hepatitis B virus infection (i.e., HBsAg negative, anti-HBc positive, and HBV DNA negative tests prior to enrollment) are eligible for this trial. Anti-HCV antibody positive will be eligible only if PCR is negative for HCV RNA.
  • Known active tuberculosis (history of exposure or history of positive TB test plus presence of clinical symptoms, physical or radiographic findings).
  • Known positivity to the human immunodeficiency virus (HIV) or active acquired immunodeficiency syndrome (AIDS). Patients on effective anti-retroviral therapy with undetectable viral load and CD4 count >200/unit are eligible for this trial.
  • Concomitant or prior use within 2 weeks before start of study treatment of strong inhibitors and inducers of CYP3A4 activity (listed in APPENDIX B). Note: inducers and inhibitors of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce or inhibit CYP3A4, should be considered.
  • Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids. Note: prophylactic anticoagulation as follows is allowed: low dose warfarin
  • (1 mg orally, once daily) with PT-INR . 1.5 x ULN is permitted. Infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on regorafenib therapy. Therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes; low dose aspirin (. 100 mg daily); prophylactic doses of heparin.
  • Use of any herbal remedy that may unsafely interact with study drugs at the discretion of the treating provider or PI (e.g. St. John fs wort [Hypericum perforatum]).
  • Active pregnancy or nursing. Pregnant women are excluded from this study because: a) effects of regorafenib on pregnancy and lactation in humans are unknown but its use is advised against since there is preclinical evidence of reproductive toxicity and fetal harm and harm to breast-fed children cannot be excluded; b) reproductive and developmental toxicology studies have not yet been conducted with lorigerlimab consistently with the expectations for this early phase of clinical development in accordance with ICH S6(R1) (2011) and ICH M3(R2) (2009).
  • Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the Lorigerlimab drug formulation.

About this study

Official title: Phase II Trial of Regorafenib Plus Lorigerlimab in Patients With Locally Recurrent or Regrowing pMMR/MSS Localized Rectal Cancer

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.

Read the detailed description

Primary Objective:

To assess the major pathological response (MPR) rate following regorafenib plus lorigerlimab and surgical resection in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy. MPR is defined as residual (viable) invasive cancer cells of 0 - 49% within the resected specimen at the time of surgical resection.

Secondary Objectives:

To estimate overall response rate (ORR) based on RECIST 1.1 following regorafenib and lorigerlimab in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy.

  • To estimate immune-related objective response rate (irORR) based on irRECIST following regorafenib and lorigerlimab in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy.
  • To describe the R0 resection rate following neoadjuvant regorafenib plus lorigerlimab and surgical resection in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy.
  • To summarize pathological response (% tumor viability, ypTNM) in surgically resected specimens following regorafenib and lorigerlimab in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy.
  • To estimate time to surgical resection following regorafenib and lorigerlimab in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy.
  • To estimate permanent ostomy rate following regorafenib and lorigerlimab in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy.
  • To estimate clinical complete response rate following regorafenib and lorigerlimab in patients with locally recurrent or regrowing pMMR/MSS localized rectal cancer after completion of total neoadjuvant therapy.
Being tested
Regorafenib, Lorigerlimab
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RegorafenibDrug

    Also called Stivarga

    Given by mouth

  • LorigerlimabDrug

    Also called MGD019

    Give by IV infusion

Study groups in NCT07223567
Study groupRoleWhat they receive
Treatment with Regorafenib PO + Lorigerlimab IV Q4WExperimentalParticipants 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.
Receives: Drug: Regorafenib; Drug: Lorigerlimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Through study completion; an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2025
  2. Study start27 Oct 2025
  3. Primary completion22 Jan 2026
  4. Study completion22 Jan 2026

Why it stopped: 0 participants enrolled

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07223567
Sponsor's protocol ID
2025-0809
Other IDs
NCI-2025-08120
Status last verified
Feb 2026
First submitted
30 Oct 2025
Last updated
25 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib and Lorigerlimab in people with Rectal Cancer and Rectal Cancer Recurrent, run by M.D. Anderson Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07223567.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.

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