Phase II Clinical Study of RC148 (ABBV-1480) in Combination With Telisotuzumab Adizutecan (With or Without Chemotherapy) for Unresectable Colorectal Cancer

Prior treatment

• History of interstitial lung disease or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD/pneumonitis on screening chest CT scan
• Active inflammatory bowel disease (including but not limited to ulcerative colitis and Crohn's disease; Abdominal fistula, GI perforation, peptic ulcer, or intra-abdominal abscess within 6 months prior to the first dose; Imaging evidence of gastrointestinal obstruction or clinical symptoms and signs of gastrointestinal obstruction
• Active gastrointestinal bleeding, hemoptysis , peptic ulcer, or bleeding events requiring intervention within 28 days prior to the first dose; or had severe esophageal and gastric varices, epistaxis , or clinically significant coagulopathy
• Toxicity not recovered from prior anticancer therapy, defined as not recovered to NCI CTCAE v6.0 Grade 1 or baseline level, or at the level specified in the inclusion/exclusion criteria,s.
• Prior systemic regimen containing Irinotecan or c-Met targeting antibody or c-Met targeting ADC, or any Top1i ADC
• Received any prior tumor immunotherapy
• Participants treated with any investigational treatment within 28 days or 5 half-lives of the treatment prior to the first dose of study treatment or is currently enrolled in another clinical study or was previously enrolled in this study
• Received chest radiotherapy of \> 30 Gy within 6 months prior to the first dose and/or received palliative local therapy within 2 weeks prior to the first dose
• Received nonspecific immunomodulatory therapy or received herbal supplements or traditional Chinese medicines that are intending to treat cancer within 1 weeks prior to the first dose of study drugs
• Participant has received any live vaccine within 4 weeks prior to the first dose of study treatment, or expected need of live vaccination during study participation including at least 4 weeks after the last dose of study treatment
• Systemic treatment with corticosteroids or other immunosuppressive drugs within 2 weeks prior to the first dose of study drugs
• Participants receiving anticoagulant drugs.
• Major surgical procedure within 28 days, or anticipation of the need for major surgical procedure during the study, and minor surgical procedure within 7 days prior to study enrollment

Other illness

• The images during the screening indicating obvious necrosis or cavity in tumor that may increase the risk of hemorrhage as determined by investigators, tumor invasion of major blood vessels or vital organs, the risk of fistula, or tumor encasing major blood vessels, or imaging evidence indicating participating in the study may increase the risk of hemorrhage
• History of idiopathic pulmonary fibrosis, organizing pneumonia, treatment-induced pneumonitis, idiopathic pneumonitis, or radiation pneumonitis
• History of clinically significant, intercurrent lung-specific illnesses including
• Uncontrollable cardiovascular diseases
• Ongoing serious, non-healing wound, ulcer, or bone fracture
• History of clinically significant arterial thrombotic or embolic events e.g., deep venous thrombosis, pulmonary embolism or cerebral vascular accident
• Serious acute or chronic infections
• History of liver cirrhosis
• Uncontrolled diabetes
• Active or history of autoimmune diseases that may relapse.
• History of other acquired or congenital immunodeficiency diseases or organ transplantation.
• Known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
• History of an allergic reaction or significant sensitivity to constituents of the study treatment and/or other products in the same class

Lab values

• Have any other diseases, metabolic abnormalities, abnormal physical examinations or laboratory tests, indicating reasonable possibility, as determined by investigators, that the participants have diseases or conditions disqualified him/her for the investigational drugs, the interpretation of the study results may be impacted, or the participants may be put at high risk

Other

• Participants are dMMR/MSI-H or have known BRAF V600E mutation
• Known active CNS metastases and/or carcinomatous meningitis.
• Third space effusion with clinical symptoms or requiring intervention.

• Voluntarily participate in the study and sign the informed consent form
• Be willing to and able to act on the trial and the follow-up procedures
• At least 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Participants have histologically or cytologically confirmed unresectable adenocarcinoma of the colon or rectum
• At least one lesion with measurable disease based on RECIST v1.1 as determined by the local site investigator/radiology assessment
• All participants must have an evaluable c-Met expression result per central IHC testing, a RAS status report, and a MSI/MMR report prior to the first dose of study treatment
• Adequate bone marrow, hepatic, renal and coagulation functions
• Female participants must be postmenopausal or surgically sterilized, or must have a negative blood pregnancy test within 7 days prior to the first dose for women of childbearing potential, and agree to take at least one medically accepted contraceptive measure during the treatment and within 12 months following the end of treatment, and must not donate eggs or breast-feeding. Male participants must agree to take at least one medically accepted contraceptive measure during the treatment period and within 12 months following the end of treatment, and must not donate sperm during this period