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.
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.
• 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.