Rectal CancerPhase 2PANTHERNCT05024097
A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for Rectal Cancer.
A Phase 2 study testing Etrumadenant (AB928), Radiation therapy and FOLFOX regimen in people with Rectal Cancer, run by Weill Medical College of Cornell University at 3 sites in United States.
Trial summary
Enrolled patients will receive upfront (week 1) short-course radiotherapy to gross pelvic disease (25Gy in 5fx) in combination with AB928 (150 mg orally, once daily as part of a continuous dose regimen). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Etrumadenant (AB928), Radiation therapy and FOLFOX regimen
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 3 sitesUnited States
- Study dates
- 31 Mar 2022to Dec 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Weill Cornell Medical College
New York, New York, 10065
Encouse Golden, M.D.,Ph.D., 212-746-3650, eng2003@med.cornell.edu
Fabiana Gregucci, M.D., 646-962-3110, fgr4002@med.cornell.edu
- Recruiting
Brooklyn Methodist Hospital - NewYork Presbyterian
New York, New York, 11215
Mary Palmer, M.S., map9505@med.cornell.edu
Hani Ashamalla, M.D.
- Recruiting
New York Presbyterian Hospital - Queens
New York, New York, 11355
Hina Ali, M.D., 718-670-1541, hia4002@med.cornell.edu
Andrew Brandmaier, M.D.
About this study
Enrolled patients will receive upfront (week 1) short-course radiotherapy to gross pelvic disease (25Gy in 5fx) in combination with AB928 (150 mg orally, once daily as part of a continuous dose regimen). This will be followed by consolidation chemotherapy (weeks 3-20) with mFOLFOX x9 cycles in combination with AB928 and AB122.
Read the detailed description
Enrolled patients will receive upfront (week 1) short-course radiotherapy to gross pelvic disease (25Gy in 5fx) in combination with AB928 (150 mg orally, once daily as part of a continuous dose regimen). This will be followed by consolidation chemotherapy (weeks 3-20) with mFOLFOX x9 cycles in combination with AB928 and AB122. Patients will thereafter be assessed for therapeutic responses (week 22-24) with a digital rectal examination, pelvic MRI, and endoscopy. Each case will be reviewed by the Weill Cornell Medicine Colorectal Multidisciplinary Tumor Board for consensus agreement regarding clinical treatment response. The patients thereafter will proceed with total mesorectal excision (TME, week 24) by transabdominal resection for pathologic evaluation (primary tumor and pelvic lymph nodes will be examined).
- Conditions
- Rectal Cancer
- Being tested
- Etrumadenant (AB928), Radiation therapy, FOLFOX regimen, Zimberelimab (AB122)
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Etrumadenant (AB928)Drug
Patients will receive a radiation therapy dose of 25Gy in 5 fractions in combination with etrumadenant 150 mg orally, once daily as part of a continuous dose regimen.
Radiation therapyRadiation
Patients will receive a radiation therapy dose of 25Gy in 5fx
FOLFOX regimenDrug
After completing the radiation therapy, patients will receive FOLFOX regimen for 9 cycles in combination with etrumadenant and zimberelimab. All patients will be offered adjuvant zimberelimab for up to one year.
Zimberelimab (AB122)Drug
After completing the radiation therapy, patients will receive FOLFOX regimen for 9 cycles in combination with etrumadenant and zimberelimab. All patients will be offered adjuvant zimberelimab for up to one year.
| Study group | Role | What they receive |
|---|---|---|
| Radiation therapy and etrumadenant (AB928) | Experimental | Enrolled patients will receive Radiation therapy of 25 Gy in 5 fractions along with etrumadenant 150mg oral drug taken once daily. this will then be followed by 9 cycles of FOLFOX in combination of etrumadenant and zimberelimab investigational drugs. Receives: Drug: Etrumadenant (AB928); Radiation: Radiation therapy; Drug: FOLFOX regimen; Drug: Zimberelimab (AB122) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of treated patients who achieve complete pathologic response
The primary endpoint is the proportion of treated rectal cancer patients who achieve a complete pathologic response.
All patients will be offered surgical resection however those who achieve a clinical CR at the time of clinical response assessment may choose a non-operative management approach. Due to practicality the latter will be included as complete responders at the time of analysis for this trial.
Measured: Week 24
Secondary outcomes (7)
Number of patients who experience treatment-related adverse events
Number of patients with treatment-related early and late adverse events as assessed by the CTCAE version 5.0
Measured: Day 5 of radiation therapy
Number of patients who experience treatment-related adverse events
Number of patients with treatment-related early and late adverse events as assessed by the CTCAE version 5.0
Measured: 3 months
Number of patients who experience treatment-related adverse events
Number of patients with treatment-related early and late adverse events as assessed by the CTCAE version 5.0
Measured: 6 months
Number of patients who experience treatment-related adverse events
Number of patients with treatment-related early and late adverse events as assessed by the CTCAE version 5.0
Measured: 12 months
Number of patients who experience treatment-related adverse events
Number of patients with treatment-related early and late adverse events as assessed by the CTCAE version 5.0
Measured: 60 months
Progression free survival
PFS is defined as the duration of time from start of treatment to time of progression.
Measured: 36 months
Overall survival
Overall Survival is defined as the duration of time from start of treatment until death.
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start31 Mar 2022
- Primary completionDec 2026 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 43 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Arcus Biosciences, Inc.
- Responsible party
- Sponsor
- Investigators
- Encouse Golden, M.D., Ph.D., Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05024097
- Sponsor's protocol ID
- 21-02023289
- Acronym
- PANTHER
- Status last verified
- Jul 2026
- First submitted
- 20 Aug 2021
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for Rectal Cancer.
- ClinicalTrials.gov ID
- NCT05024097
- Acronym / sponsor ID
- PANTHER / 21-02023289
- Conditions
- Rectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 43 participants (estimated)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Arcus Biosciences, Inc.
- Study start
- 31 Mar 2022 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 27 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Enrolled patients will receive upfront (week 1) short-course radiotherapy to gross pelvic disease (25Gy in 5fx) in combination with AB928 (150 mg orally, once daily as part of a continuous dose regimen). This will be followed by consolidation chemotherapy (weeks 3-20) with mFOLFOX x9 cycles in combination with AB928 and AB122.
Detailed description
Enrolled patients will receive upfront (week 1) short-course radiotherapy to gross pelvic disease (25Gy in 5fx) in combination with AB928 (150 mg orally, once daily as part of a continuous dose regimen). This will be followed by consolidation chemotherapy (weeks 3-20) with mFOLFOX x9 cycles in combination with AB928 and AB122. Patients will thereafter be assessed for therapeutic responses (week 22-24) with a digital rectal examination, pelvic MRI, and endoscopy. Each case will be reviewed by the Weill Cornell Medicine Colorectal Multidisciplinary Tumor Board for consensus agreement regarding clinical treatment response. The patients thereafter will proceed with total mesorectal excision (TME, week 24) by transabdominal resection for pathologic evaluation (primary tumor and pelvic lymph nodes will be examined).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiation therapy and etrumadenant (AB928) | Experimental | Drug: Etrumadenant (AB928), Radiation: Radiation therapy, Drug: FOLFOX regimen, Drug: Zimberelimab (AB122)Enrolled patients will receive Radiation therapy of 25 Gy in 5 fractions along with etrumadenant 150mg oral drug taken once daily. this will then be followed by 9 cycles of FOLFOX in combination of etrumadenant and zimberelimab investigational drugs. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Etrumadenant (AB928)Patients will receive a radiation therapy dose of 25Gy in 5 fractions in combination with etrumadenant 150 mg orally, once daily as part of a continuous dose regimen. | Drug | Radiation therapy and etrumadenant (AB928) |
| Radiation therapyPatients will receive a radiation therapy dose of 25Gy in 5fx | Radiation | Radiation therapy and etrumadenant (AB928) |
| FOLFOX regimenAfter completing the radiation therapy, patients will receive FOLFOX regimen for 9 cycles in combination with etrumadenant and zimberelimab. All patients will be offered adjuvant zimberelimab for up to one year. | Drug | Radiation therapy and etrumadenant (AB928) |
| Zimberelimab (AB122)After completing the radiation therapy, patients will receive FOLFOX regimen for 9 cycles in combination with etrumadenant and zimberelimab. All patients will be offered adjuvant zimberelimab for up to one year. | Drug | Radiation therapy and etrumadenant (AB928) |
Primary outcome
Number of treated patients who achieve complete pathologic response
Time frame: Week 24
The primary endpoint is the proportion of treated rectal cancer patients who achieve a complete pathologic response. All patients will be offered surgical resection however those who achieve a clinical CR at the time of clinical response assessment may choose a non-operative management approach. Due to practicality the latter will be included as complete responders at the time of analysis for this trial.
7 secondary outcomes
Number of patients who experience treatment-related adverse events
Time frame: Day 5 of radiation therapy
Number of patients who experience treatment-related adverse events
Time frame: 3 months
Number of patients who experience treatment-related adverse events
Time frame: 6 months
Number of patients who experience treatment-related adverse events
Time frame: 12 months
Number of patients who experience treatment-related adverse events
Time frame: 60 months
Progression free survival
Time frame: 36 months
Overall survival
Time frame: 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Encouse Golden, M.D., Ph.D. principal investigator
Weill Medical College of Cornell University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etrumadenant (AB928), Radiation therapy and FOLFOX regimen in people with Rectal Cancer, run by Weill Medical College of Cornell University at 3 sites in United States.
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 16 inclusion and 29 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: looking for participants now, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fabiana Gregucci, M.D. (646- 962-3110, fgr4002@med.cornell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of treated patients who achieve complete pathologic response (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jul 2026.