CytomX Therapeutics reported an update the other day relating to its phase 1 CTMX-2051-101 trial, which is using its antibody-drug conjugate (ADC) CX-2051 to treat patients with advanced metastatic colorectal cancer. It noted that there was one patient who had died from a Grade 5 treatment-related acute kidney injury event. The death of a patient is never a good thing, but the company did right by quickly taking the necessary action when such a situation arose. As soon as it learned about this event on July 11, 2025, it immediately reported it to the FDA thereafter on July 18, 2025. Besides this, it had to take another measure to ensure that patients could continue to be dosed with this ADC in this early-stage trial going forward.
It also had to report the patient death to a Safety Review Committee as well, and this was ultimately established several days after the patient death on July 14, 2025. After this committee reviewed the report about what had happened, it concluded that it was okay to keep the study going. It’s important to highlight that even though the committee agreed to allow this study to continue, there is no way of knowing later on whether or not the FDA will decide to halt it. For now, this CTMX-2051-101 study will continue to dose patients, and this is important because it brings about an important catalyst for investors to look forward to. The goal of the company is to release data from this specific trial in Q1 of 2026.
Colorectal cancer (CRC) is a devastating disease whereby there is the growth of malignant cells on the colon or rectum of a patient. The truth is that it is best when this type of cancer is found early on, but sometimes the disease has progressed to a late stage. This is important to bring up because the goal of CytomX is to target late-line metastatic CRC patients. With that being said, the characteristic of the phase 1 CTMX-2051-101 study was to enroll patients who had a median of 4 prior lines of therapy before being enrolled into this trial. In essence, these were 5th-line patients that were given a monotherapy dose of CX-2051.
Once every 3 weeks (Q3W), these patients were given doses of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg. The significance of this is that the use of these three doses of drug entails the dose-expansion portion of the ongoing phase 1 study. The hope is that it can do well in treating these advanced CRC patients, because at the moment 3rd-line + therapy response rates are very bad. The most effective therapy is trifluridine/tipiracil (Lonsurf) plus Avastin (bevacizumab), which is able to achieve a 6% objective response rate (ORR). All other 3rd-line or later therapies have lower response rate numbers. Along with the fact that they provide poor progression-free survival (PFS) rates as well.
The science of this company revolves around its Probody technology, which is to develop candidates that selectively bind only to tumors and avoid having to do so with healthy tissues. The bottom line is that there is a “mask” in place, and when the drug enters the tumor microenvironment (TME), it ends up being cleaved by the substrate itself and in turn allows the binding to the cancer cell I just noted. As far as the mechanism of action (MOA) of CX-2051, it is an ADC that only activates when it reaches type I transmembrane glycoprotein Epithelial Cell Adhesion Molecule (EpCAM). With EpCAM being found in both healthy adult tissue and cancer cells, this is why the Probody technology is important. The end result is the ADC activating upon impact with EpCAM and releasing a topoisomerase-1 inhibitor payload. The thing is that this ADC was developed in collaboration with ImmunoGen.
Earlier this year in January, the company made a bold move to reprioritize its pipeline, and this involved the emphasis of continuing on with lead candidate CX-2051 to treat patients with several EpCAM tumors. This makes sense based on the phase 1 data it has achieved to date. Not only that, but this protein is highly expressed in many other types of cancers. With two other likely high-valued targets being ovarian cancer and NSCLC, where EpCAM expression in these are 83% and 80%, respectively. In addition to this move, it also reduced its workforce by 40% to narrow in on CX-2051 and other partnered assets. It has ongoing collaborations with many other big pharmaceutical companies like Bristol-Myers Squibb, Moderna, Regeneron, and Astellas.
One of the more recent partnerships is with Merck to advance the use of PROBODY Interferon alpha-2b CX-801 in combination with Keytruda to treat patients with advanced melanoma. Results from this early-stage study, using this combination to treat patients with advanced melanoma, are expected in 2026. Separately, CytomX is exploring the use of this drug as a monotherapy in an ongoing phase 1 dose-escalation study in the targeting of patients with advanced solid tumors. Preliminary data from this early-stage study is anticipated in Q4 of 2025.