Phase II Clinical Trial of FOLFOX, Botensilimab, Plus Balstilimab in Patients With Localized Rectal Cancer
This phase II trial tests how well fluorouracil, oxaliplatin and leucovorin calcium (folinic acid) (FOLFOX) with botensilimab and balstilimab given before surgery (neoadjuvant) works in treating patients with rectal adenocarcinoma that has not spread to other parts of the body (localized). Currently, neoadjuvant therapy for rectal cancer includes chemotherapy and chemoradiation. Despite these aggressive treatments, only about half of patients achieve a complete clinical response. In fact, over half of rectal cancer patients go on to have surgery and often suffer post-surgery complications involving urine and bowel problems. Thus, there has been an increased focus on non-surgical treatments. Chemotherapy drugs, such as fluorouracil, oxaliplatin and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant FOLFOX with botensilimab and balstilimab may improve the rate of complete response and decrease the need for surgery and radiation therapy in patients with localized rectal adenocarcinoma.
• Documented informed consent of the participant and/or legally authorized representative
⁃ Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
⁃ If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Histologically confirmed adenocarcinoma of the rectum
• Rectal involvement defined as involvement of the rectum within 12 cm proximal from anal verge
• Radial margin of at least 3mm from the mesorectal fascia, with no threatened circumferential tumor margin based on MRI. No more than 4 lymph nodes (LN) with short axis \> 1 cm
• T3N0, or TxN1 or TxN2 clinical stage based on MRI staging
• No evidence of distant metastatic disease based on imaging studies including CT chest and CT or MRI of abdomen and pelvis
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
• Without bone marrow involvement: Platelets ≥ 100,000/mm\^3
• Hemoglobin ≥ 9g/dL
⁃ NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)
• Aspartate aminotransferase (AST) ≤ 3.0 x ULN
• Alanine aminotransferase (ALT) ≤ 3.0 x ULN
• Creatinine \< 1.5 x ULN or clearance of ≥ 40 mL/min per 24 hour urine test or the Cockcroft-Gault formula
• Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test
⁃ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 9 months for women, and at least 6 months for men, after the last dose of oxaliplatin therapy. If patients discontinue oxaliplatin more than 9 months (females) or 6 months (males) before discontinuation of balstilimab and/or botensilimab, females and males of childbearing potential must use an effective method of birth control or abstain from sexual activity for the course of the study through at least 120 days after the last dose of balstilimab and/or botensilimab
⁃ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)