First Patient Dosed With CX-801 Plus Keytruda in Metastatic Melanoma

The first patient has received CX-801 plus Keytruda in a phase 1 trial for metastatic melanoma: © stock.adobe.com.

The first patient has been dosed with CX-801 in combination with Keytruda (pembrolizumab) in an ongoing phase 1 dose escalation study, which is evaluating the safety and initial clinical activity of the agent in patients with metastatic melanoma, according to a news release from CytomX Therapeutics.

Following initial success with CX-801 alone, CytomX has launched the combination arm of a phase 1 trial testing CX-801 with Keytruda in metastatic melanoma

“We are excited to begin evaluating this combination therapy that has the potential to provide significant clinical benefit to patients with PD-1 refractory melanoma, which remains an area of high unmet need,” Dr. Wayne Chu, chief medical officer of CytomX Therapeutics, said in the news release. “Utilizing CytomX’s proprietary conditional activation platform to maintain potency and widen interferon’s therapeutic index, CX-801 is well suited to combine with Keytruda and could become an important component of combination immuno-oncology therapy. We look forward to initial phase 1a translational and biomarker data in advanced melanoma in the second half of 2025.”

The study is being conducted at two locations in the United States. In California, the site is the University of California San Francisco, located in San Francisco, where the study is not yet recruiting. In Pennsylvania, the trial is actively recruiting participants at the University of Pittsburgh Hillman Cancer Center in Pittsburgh.

The study has two parts: Part 1 is a dose-escalation phase to determine the highest tolerated dose of CX-801, both alone and with Keytruda. Part 2 is a dose-expansion phase to further evaluate the safety and tolerability of the combination and explore its antitumor activity in specific cancer types. Both parts include a study time frame of 44 months.

Secondary outcomes during the trial include objective response rate, duration of response, progression-free survival, disease control rate, duration of disease control and overall survival. Secondary outcome measures have a time frame of 60 months.

CX-801 is an investigational drug designed to activate the immune system against cancer by targeting tumors more precisely. It builds on the known anti-cancer effects of interferon alpha-2b, a type of immune-stimulating protein, but aims to reduce the harmful side effects that can occur when the drug spreads throughout the body. By using a masking technology, CX-801 focuses its activity inside tumors, potentially making it safer and more effective — especially when used alongside treatments like checkpoint inhibitors.

Inclusion and Exclusion Criteria

Participants must have metastatic or locally advanced solid tumors that cannot be surgically removed and have worsened after standard treatments. They must have an Eastern Cooperative Oncology Group performance status of 0 (fully active) or 1 (restricted activity) and measurable disease based on RECIST version 1.1. Patients must agree to a fresh biopsy or provide tumor tissue collected within the past six months if a new biopsy is not medically possible. Adequate organ function is required. Additional eligibility criteria may apply.

Patients will be excluded if they have had a different localized cancer within the past two years, known active cancer in the brain or spinal cord, or previously stopped immunotherapy due to severe immune-related side effects. Other exclusions include recent anticancer treatment (within four weeks or five half-lives), use of investigational drugs or devices within four weeks, radiation within two weeks, serious current illnesses or pregnancy or breastfeeding. Additional exclusion criteria may apply.

For more information regarding the phase 1a trial, please visit www.clinicaltrials.gov using the identifier: NCT06462794.

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