Study Sponsor: Tizona Therapeutics, Inc.

Location: HealthPartners Cancer Center at Regions Hospital

Phase of Study: Phase I

Purpose of study: The purpose of the study is to assess the safety and determine the good and bad effects of an investigational drug called TTX-080 (the study drug). The purpose of this study is to understand how subjects with colorectal cancer might benefit from TTX-080 in combination with FOLFIRI (leucovorin calcium (folinic acid), fluorouracil (5- FU), and irinotecan hydrochloride) and cetuximab (approved treatments for colorectal cancer). TTX-080 is an antibody made in a laboratory and binds to a protein called HLA-G and blocks its suppressive function. Antibodies are naturally made by the body in reaction against foreign substances (such as bacteria and viruses) that get in the body. Some cells use HLA-G to suppress the body’s immune system response and help cancer cells grow. By blocking HLA-G, TTX-080 may help the immune system attack cancer cells. Cetuximab and FOLFIRI are approved by the FDA in the USA, and they are available by prescription to treat colorectal cancer. Cetuximab, a monoclonal antibody belonging to class of targeted agents, works by blocking a key protein called epidermal growth factor receptor (EGFR) found on the cancer cell surface. It may also help the immune system to fight cancer. FOLFIRI is a combination of chemotherapy treatments that works by destroying cancer cells.

Inclusion Criteria:
– Male or female patients ≥ 18 years of age at the time of screening.
– Histological or cytological diagnosis of mCRC that is considered incurable.
– Tumors must be MSS, WT for RAS, WT for BRAF, and HER2-negative. Results from local testing will be accepted for enrollment but tumor samples must be submitted for central confirmation within 30 days after study enrollment
– Patient must have previously received 5-fluorouracil and oxaliplatin-based chemotherapy with or without bevacizumab in the frontline setting for mCRC. Patients who received FOLFOX in the adjuvant setting will be eligible if the tumor relapses within 6 months of stopping treatment.
– Patients must NOT have received prior irinotecan, or anti-EGFR therapy such as cetuximab, or panitumumab but be eligible to receive cetuximab per approved label regarding tumor RAS status
– Patients must be able to provide adequate amount of tumor tissue for central laboratory testing of MSS, RAS, BRAF, and HER2 status
– At least 1 measurable lesion per RECIST 1.1
– ECOG of 0 – 1.
– Life expectancy of at least 12 weeks.
– Adequate organ function as determined by local lab tests.
– Must use highly effective methods of contraception through 120 days after last dose of study treatment.

Additional criteria may apply and will be discussed with the treating physician and study team.

Exclusion Criteria:
-Active brain or leptomeningeal metastases. patients may be able to participate if radiologically and clinically stable for at least 4 weeks.
-Patients who are at risk of life-threatening complications in the short term (uncontrolled effusions, pulmonary lymphangitis).
-Patients with other active malignancy within 3 years prior to enrolling in study. (some exceptions may apply such as non-melanoma skin cancer, superficial bladder cancer, carcinoma in situ of breast or cervix, localized prostate cancer in remission, or other non-invasive or indolent malignancy).
-Major surgery within 4 weeks prior to receiving first dose of study drug.
-Excluded if patient has received systemic anticancer therapy within 4 weeks prior to first dose.
-Active Hepatitis B or C infection.
-Uncontrolled pleural, pericardial effusion, or ascites that requires draining more than once every 28 days.
– Active known or suspected autoimmune disease, or if receiving immunosuppression for organ transplant.
– significant cardiac arrhythmias within the last 6 months, NYHA class III or IV congestive heart failure, or ongoing cardiac arrhythmias of Grade 2 or higher, or any grade of atrial fibrillation.
– Hypertension that requires more than 2 medications to control.
– participation in other studies involving investigational drugs within the last 28 days prior to first dose.
– History of allergy or hypersensitivity to study medication or its components.
– Women who are pregnant or breastfeeding.
Additional criteria may apply and will be discussed with the treating physician and study team.

Study Contact:
Lisa Wahowske , RN OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com