Phase II Trial of CBX-12 for Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer
Study Description
This phase II trial studies how well CBX-12 works in treating patients with microsatellite stable colorectal cancer that has spread to other parts of the body (metastatic) and is no longer responding to chemotherapy treatment (chemotherapy-refractory). The usual approach to treating colorectal cancer includes treatment with surgery, radiation, or Food and Drug Administration (FDA)-approved drugs such as trifluridine-tipiracil, bevacizumab, regorafenib, or fruquintinib. However, most metastatic colorectal patients progress through all approved treatments and eventually succumb to their disease. CBX-12 is a drug that contains a peptide (a substance that contains many amino acids [molecules that join together to form proteins]) called pHLIP, linked to an anticancer substance called exatecan. Upon administration, pHLIP gets inserted into the cellular membrane of tumor cells, delivering exatecan to kill them. Giving CBX-12 may work better than the usual approach in treating patients with metastatic chemotherapy-refractory microsatellite stable colorectal cancer.
Eligibility
-Patients must have histologically or cytologically confirmed metastatic colorectal cancer (mCRC) that is mismatch repair proficient (pMMR) based on local testing performed in a Clinical Laboratory Improvement Act (CLIA) lab
-Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam
-Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment, with no Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 toxicity of grade 3 or higher at the time of enrollment
-Availability of archival tumor tissue at the time of patient enrollment for molecular profiling studies
-Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
-Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CBX-12
- Patients with concurrent administration of medication expected to cause drug interactions with CBX-12, including strong inducers and strong inhibitors of CYP3A4/1A2 isoenzymes or sensitive substrates of CYP3A4/2B6, OATP1B1, OATP1B3, OAT1, and MATE-2k
-Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
-Pregnant women are excluded from this study because CBX-12 is a topoisomerase 1 inhibitors agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CBX-12, breastfeeding should be discontinued if the mother during treatment with CBX-12 and for at least 4 months after the last dose of CBX-12. Male patients treated with CBX-12 should use effective contraception and avoid fathering a child during and up to 4 months after treatment
