CytomX Therapeutics announced today that the first patient has been dosed in the combination arm of its ongoing Phase 1 clinical trial evaluating CX-801 in combination with Keytruda (pembrolizumab) for the treatment of patients with metastatic melanoma.
The clinical trial is designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CX-801 when administered alongside Merck's PD-1 inhibitor pembrolizumab, which has become a standard of care in melanoma treatment.
"Dosing the first patient in this combination arm represents an important milestone in our clinical development program for CX-801," said a senior executive from CytomX Therapeutics. "We are excited to explore how our investigational therapy may work synergistically with pembrolizumab to potentially improve outcomes for patients with metastatic melanoma."
Study Design and Patient Population
The Phase 1 study is structured as a multi-arm trial, with the newly initiated combination arm specifically targeting patients with metastatic melanoma who have not responded adequately to prior therapies. The trial will enroll patients across multiple clinical sites in the United States.
Patients in the combination arm will receive CX-801 at predetermined dose levels alongside the standard approved dose of pembrolizumab. The study will follow a dose-escalation protocol to determine the recommended Phase 2 dose for the combination.
About CX-801
CX-801 is CytomX's investigational conditionally activated therapeutic designed to enhance anti-tumor immune responses. While specific details about the mechanism of action were not fully disclosed, the company's platform typically involves proteolytically-activated therapeutics that are designed to be activated within the tumor microenvironment.
This approach aims to minimize systemic toxicity while maximizing therapeutic activity at the tumor site, potentially addressing some of the limitations of current immunotherapies.
Metastatic Melanoma: Unmet Medical Needs
Metastatic melanoma remains a challenging disease despite recent advances in immunotherapy. According to recent epidemiological data, melanoma accounts for approximately 1% of all skin cancers but is responsible for the majority of skin cancer deaths. The American Cancer Society estimates that about 100,350 new melanomas will be diagnosed in the United States annually, with about 6,850 people expected to die from the disease.
While PD-1 inhibitors like pembrolizumab have revolutionized the treatment landscape for melanoma, a significant proportion of patients either do not respond to these therapies or develop resistance over time, highlighting the need for novel combination approaches.
Potential Impact of the Combination Approach
The scientific rationale for combining CX-801 with pembrolizumab stems from the hypothesis that CX-801's mechanism may complement the immune-activating properties of PD-1 inhibition, potentially leading to enhanced anti-tumor activity.
"Despite the advances we've seen with checkpoint inhibitors in melanoma, there remains a substantial unmet need for patients who don't respond to or relapse after initial immunotherapy," noted a clinical investigator involved in the trial. "Novel combination approaches like this one are critical to improving outcomes for these patients."
Looking Forward
CytomX expects to report preliminary data from this combination arm in the latter half of 2025. These results will inform future development decisions, including potential expansion into additional tumor types or combination strategies.
The company has indicated that if the results prove promising, they plan to rapidly advance the combination into a more extensive Phase 2 program, potentially exploring biomarkers that might predict which patients are most likely to benefit from the approach.
This clinical trial adds to the growing landscape of innovative combination strategies being explored to overcome resistance to immunotherapy and improve outcomes for patients with advanced cancers.
