A Phase II Study to Test the Efficacy of AB928 (Dual Adenosine Receptor Antagonist) and AB122 (a PD1 Checkpoint Inhibitor) in Combination With Short Course Radiotherapy and Consolidation Chemotherapy for Rectal Cancer (PANTHER)

Clinical Trial Details

The purpose of the study is to see if short course radiation treatment to the tumor combined with two investigational drugs AB928 and AB122 will help in eliminating the tumor and thereby increase response to the treatment in patients with rectal cancer.

AB928 is an oral dual antagonist (have opposing actions) of the adenosine 2a receptor and the adenosine 2b receptor. Adenosine has the ability to inhibit the activation of various immune cell types, present at high concentrations in many tumors and may play an important role in creating a weak immune system (immunosuppressed). The rationale for AB928 is based on the observation that most tumors contain high levels of adenosine that leads to activation of A2aR and A2bR on T cells and myeloid cells, respectively, impairing T-cell activation and proliferation. Therefore, blocking the adenosine receptors with AB928 reverses these immunosuppressive effects.

AB122 is fully human monoclonal antibody (mAb) given through an IV that targets the human programmed cell death-1 (PD-1) immune checkpoint on T-cells. Tumor cells express the ligand for PD-1 (PD-L1), thereby impairing T-cell activation and proliferation in the tumor microenvironment. Therefore, blocking PD-1 with AB122 prevents the immunosuppressing effects tumor cells that express PD-L1.

Both AB928 and AB122 are investigational drugs, meaning they are not yet approved by the U.S. Food and Drug Administration for the treatment of rectal cancer. Emerging data show that AB928 administered together with AB122 was well tolerated and demonstrated evidence of clinical benefit, including antitumor response and disease stabilization for more than 6 months in heavily pretreated participants across multiple disease indications.

Combining radiotherapy and immunotherapy is promising and has advantages. Since radiation therapy is given to a particular area in your body it does not have many side effects that are commonly seen in patients receiving chemotherapy. In addition, radiation therapy limits the interference in patients receiving additional therapies.

Participation in this study will last approximately 5 years with regular follow ups every 3 months. All participants will receive radiation therapy, AB928, and AB122 at intervals determined by the study doctor. Rectal exams, pelvic MRIs, endoscopies, and blood draws may also be required during follow up appointments.

Key Eligibility:

Inclusion Criteria:

Histologically confirmed diagnosis of adenocarcinoma of the rectum
Age ≥ 18 years
No prior pelvic radiation therapy, chemotherapy or surgery for rectal cancer
No infections requiring systemic antibiotic 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.

Exclusion Criteria:

Recurrent or unresectable rectal cancer
Patients receiving other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody 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.

Detailed eligibility will be reviewed when you contact the study team.

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