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Can a triple-drug cocktail after short radiation eliminate rectal cancer without surgery?

NCT ID NCT05024097

What the study statuses mean

This study's is highlighted.

Recruitment status, easiest to join first

Recruiting now This study
This trial is taking on new participants right now.
Not yet recruiting
Registered, but not yet taking participants.
By invitation only
Not open to general applications. Only people the study team invites can take part.
Paused
Paused for now. It may or may not start again.
Ongoing
Running, but no longer taking on new participants.
Completed
The trial has finished. Results may not be published yet.
Stopped early
Stopped early, before it reached the end. That can be for many reasons, including safety.
Cancelled
Cancelled before anyone took part.

Expanded access (not trials)

Expanded access
Not a trial. This treatment can be requested outside a study, case by case, for people who qualify.
Expanded access (paused)
Not a trial. The treatment can normally be requested outside a study, but is unavailable right now.
Expanded access (ended)
Not a trial. The treatment could once be requested outside a study, but no longer can.
Approved
The treatment has been approved, so it is available normally rather than through this programme.

When the status isn't known

Details not published
The full record has not been published yet, so there is little to show here.
Status unknown
This status has not been confirmed recently, so it may be out of date.

First seen Jul 29, 2026 · Last updated Jul 30, 2026 · Updated 1 time

Summary

This trial is testing whether adding two immunotherapy drugs—zimberelimab and etrumadenant—to standard chemotherapy and a short course of radiation can completely eliminate rectal cancer. Adults with locally advanced rectal cancer that has not spread will receive the treatment, and those who achieve a complete response may be able to avoid surgery. The main goal is to see how many patients have no cancer left after treatment.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance
a combination of two immunotherapy drugs (zimberelimab and etrumadenant) plus chemotherapy (FOLFOX) after short-course radiation
What this could lead to
If successful, this approach could allow some people with rectal cancer to achieve a complete remission without needing surgery.
What could go wrong
This is an early-phase trial with only 43 participants, so results may not apply to everyone. The combination of drugs can cause significant side effects, and not all patients will respond.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 43 people

The number the study aims to enrol. It can still change while the study runs.

Started

Mar 2022

Expected to finish

Dec 2031

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 to 90 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included. Inclusion Criteria: * Histologically confirmed diagnosis of adenocarcinoma of the rectum * Age ≥ 18 years * ECOG performance status 0-1 * cT3N0 or cT1-3N1 or cT4 or cN2 * 5cm from the anal verge * Rectal cancer amenable to total mesorectal excision * No evidence of distant metastases * No prior pelvic radiation therapy * No prior chemotherapy or surgery for rectal cancer * No infections requiring systemic antibiotic treatment * Hgb \>8.0 gm/dL, PLT \> 150,000/mm3, total bilirubin ≤ 1.5x upper limit of normal, AST ≤ upper limit of normal, ALT ≤ 3x upper limit of normal * Patients must read, agree to, and sign a statement of informed consent prior to participation in this study. Patients who do not read or understand English or eligible but must have the consent form bread to them in its entirety by an official translator. Informed consent for non-literate or non-English speaking patients may not be obtained by using a relative or a member of the patient's clinical team as a translator * Female participants or reproductive potential, defined as not surgically sterilized and between menarche and 1 year post menopause, must have a negative serum pregnancy test within 4 weeks prior to initiation of study treatment * Female participants of reproductive potential and male participants with female partners of reproductive potential must remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive measures from the start of study treatment until 30 days after the last dose of Etrumadenant, -120 days after the last dose of Zimberelimab, whichever is longer and duration of contraception to follow oxaliplatin should be at least 9 months after the last dose for women and 6 months after the last dose for men) * Women with childbearing potential who are negative for pregnancy (urine or blood) and who agree to use effective contraceptive methods. A woman of childbearing potential is defined by one who is biologically capable of becoming pregnant. Reliable contraception should be used from trial screening and must be continued throughout the study. * Male subjects must also agree to use effective contraception. Exclusion Criteria: * Recurrent rectal cancer * Primary unresectable rectal cancer is defined as a primary rectal tumor which, on the basis of either physical exam or pelvic MRI, is demed to be adherent or fixed to adjacent pelvic structures (en bloc resection wll not be achieved with negative margins). * Involved radial margin * Serum creatinine level \>1.5x the upper limit of normal * Patients who have received prior pelvic radiotherapy * QTc ≥480 msec using Fredericia's QT correction formula * Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had: * Treatment with known BCRP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of and throughout study treatment * Treatment with known P-gp substrates with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment * Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) and strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks (for investigational drugs when half- life is unknown or not accurately determined) or 5 drug-elimination half-lives of the drug (when half-life is determined), whichever is longer, or if it is a marketed drug, then 5 drug-elimination half-lives of the drug, prior to initiation of study treatment * Refer to the following for more examples of relevant substrates, inhibitors, and inducers with the potential for drug-drug interactions with Etrumadenant: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug- interactions-table-substrates-inhibitors-and- Inducers * Patients receiving herbal and natural remedies. Concomitant use of therapies that contain cannabinoids may be permitted based on the Investigator's discretion. * Sensitive substrates of BSEP, MATE1and OCT2. * Any gastrointestinal condition that would preclude the use of oral medications (e.g., difficulty swallowing, nausea, vomiting, or malabsorption) * Prior treatment with an agent targeting the adenosine pathway * Patients with prior allogenic stem cell or solid organ transplantation * Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy * Patients with history of idiopathic pulmonary fibrosis, pneumonitis, or interstitial lung disease * Patients receiving treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor-α agents) administered at \>10 mg/day prednisone or equivalent within 2 weeks prior to initiation of study treatment * Patients who received a live vaccine within 30 days * Patients who are known to have dihydropyrimidine dehydrogenase (DPD) deficiency * Patients with peripheral neuropathy Grade ≥ 2 * History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins * Patients with a history of any arterial thrombitic event within the past 6 months, * Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment would make them inappropriate candidates for entry into this study * Patients with a history of prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer. * Patients with a history of thrombotic episodes, such as deep venous thrombosis, pulmonary embolus, MI or CVA occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy. * Patients receiving other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibodiy therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody, or other experimental drugs) of any kind are permitted while the patient is receiving study treatment. * Women who are pregnant or breastfeeding. Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to four weeks after the study.

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Conditions

The condition(s) this trial relates to.

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

How to take part

Only the study team decides who joins. These are the ways to reach them.

  1. The places running it

    3 sites. The list below names each one and where it is.

  2. The official record

    ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

    Open the record ↗

  3. A doctor treating you

    A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

  • Brooklyn Methodist Hospital - NewYork Presbyterian

    RECRUITING

    New York, New York, 11215, United States

  • New York Presbyterian Hospital - Queens

    RECRUITING

    New York, New York, 11355, United States

  • Weill Cornell Medical College

    RECRUITING

    New York, New York, 10065, United States

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