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.

NCT05024097 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-02023289
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 3

Brief 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). This will be followed by consolidation chemotherapy (weeks 3-20) with mFOLFOX x9 cycles in combination with AB928 and AB122.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 24

Secondary Outcomes (7)

• Number of patients who experience treatment-related adverse events

  Day 5 of radiation therapy

• Number of patients who experience treatment-related adverse events

  3 months

• Number of patients who experience treatment-related adverse events

  6 months

• Number of patients who experience treatment-related adverse events

  12 months

• Number of patients who experience treatment-related adverse events

  60 months

Study Arms (1)

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.

Drug: Etrumadenant (AB928); Radiation: Radiation therapy; Drug: FOLFOX regimen; Drug: Zimberelimab (AB122)

Interventions

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 therapy and etrumadenant (AB928)

Radiation therapy RADIATION

Patients will receive a radiation therapy dose of 25Gy in 5fx

Radiation therapy and etrumadenant (AB928)

FOLFOX regimen 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.

Radiation therapy and etrumadenant (AB928)

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.

Radiation therapy and etrumadenant (AB928)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of adenocarcinoma of the rectum
• Age ≥ 18 years
• ECOG performance status 0-1
• cT3N0 or cT1-3N1 or cT4 or cN2
• cm 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (3)

Weill Cornell Medical College

New York, New York, 10065, United States

RECRUITING

Brooklyn Methodist Hospital - NewYork Presbyterian

New York, New York, 11215, United States

RECRUITING

New York Presbyterian Hospital - Queens

New York, New York, 11355, United States

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy; Folfox protocol; zimberelimab

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Encouse Golden, M.D., Ph.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabiana Gregucci, M.D.

CONTACT

646- 962-3110; fgr4002@med.cornell.edu

Dakota Trick, M.S.

CONTACT

646-962-2196; dat4015@med.cornell.edu

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: August 20, 2021
• First Posted: August 27, 2021
• Study Start: March 31, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)