WTX-124 is being evaluated as monotherapy and in combination with pembrolizumab (Keytruda) for the treatment of patients with advanced solid tumors in a phase 1/1b trial (NCT05479812). The agent is designed to produce an antitumor response by selectively providing IL-2 to the tumor microenvironment. WTX-124 is also intended to have lessened systemic toxicities that have been reported with other IL-2–directed immunotherapies.
“At Werewolf, we are focusing on efforts to address the high unmet need of [patients with] cancer, and we believe there is significant opportunity with WTX-124 for the potential treatment of advanced cancers,” Daniel J. Hicklin, PhD, president and chief executive officer of Werewolf Therapeutics, stated in a news release.
What Prior Data Have Been Reported With WTX-124?
In March 2025, Werewolf Therapeutics announced in a news release that the recommended dose for the monotherapy expansion arms of the phase 1/1b study would be WTX-124 at 18 mg given intravenously every 2 weeks for the treatment of patients with metastatic melanoma, renal cell carcinoma (RCC) and cutaneous squamous cell carcinoma (CSCC).2 This would also be the dose level of the agent in the metastatic melanoma, RCC, and non–small cell lung cancer (NSCLC) combination arms.
In the news release, the company also noted that 5 patients had experienced objective responses and that 3 of these patients continued to display no evidence of disease progression at the time of the release; 1 of these patients was treated in the monotherapy arm, and 2 were treated in the combination arm. The patient in the monotherapy arm achieved a complete response (CR) that was ongoing at more than 1 year off therapy. Moreover, 1 of the combination responses improved from a confirmed partial response to a CR, and both responses in the combination arm were ongoing for longer than 8 months.
What Were the Key Design Characteristics of the Phase 1/1b Trial?
The open-label, multicenter phase 1/1b study of WTX-124 is the first-in-human trial of the agent and is evaluating it as monotherapy and in combination with pembrolizumab in patients with advanced or metastatic solid tumors.3 In order to be eligible for enrollment, patients need to be at least 18 years old, have an ECOG performance status of 0 or 1, have a measurable lesion per RECIST 1.1 criteria, and have adequate organ and bone marrow function. Patients in the monotherapy and combination dose-escalation cohorts also need to have relapsed/refractory disease for which immunotherapy is approved and have experienced disease progression, be intolerant to standard therapy, or have no access to standard therapy with a proven benefit.
The monotherapy dose-expansion phase included 3 arms: patients with relapsed advanced or metastatic RCC who had received no more than 4 prior lines of therapy in the advanced or metastatic setting (arm A); patients with relapsed advanced or metastatic cutaneous malignant melanoma who had received no more than 2 prior lines of therapy for BRAF V600 wild-type melanoma and no more than 3 prior lines of therapy for BRAF V600–mutant melanoma (arm B); and patients with relapsed advanced or metastatic CSCC who had received no more than 1 prior line of therapy. The combination dose-expansion phase is enrolling patients with RCC who have received no more than 3 prior lines of therapy (arm D); cutaneous melanoma who are naive to all prior therapy for advanced or metastatic disease, have BRAF wild-type disease and have received no more than 2 prior lines of therapy, or have BRAF V600-mutated disease and have received no more than 3 prior lines of therapy (arm E); and PD-L1-positive NSCLC who have received no more than 3 prior lines of therapy (arm F).
The primary end points are the incidence of dose-limiting toxicities, treatment-emergent adverse effects, and changes in clinical laboratory abnormalities in the monotherapy and combination arms during the dose-escalation phase. Investigator-assessed objective response rate per RECIST 1.1 and iRECIST criteria in the monotherapy and combination arms is also a primary end point in the dose-expansion phase. Secondary end points include duration of response, progression-free survival, overall survival, and pharmacokinetic measures.
“We are encouraged by this fast track designation as an important milestone for the WTX-124 program and because it underscores the urgent need for patients with relapsed/refractory melanoma where treatment options are limited,” Hicklin added in the news release.1 “In the fourth quarter, we anticipate sharing preliminary data from the ongoing WTX-124 phase 1/1b clinical trial, including in patients with cutaneous melanoma, and engaging with the FDA regarding the potential registration strategy for this agent.”
References
- Werewolf Therapeutics receives fast track designation from the U.S. FDA for WTX-124, an investigational therapy for the treatment of cancer. News release. Werewolf Therapeutics. October 8, 2025. Accessed October 8, 2025. https://investors.werewolftx.com/news-releases/news-release-details/werewolf-therapeutics-receives-fast-track-designation-us-fda-wtx
- Werewolf Therapeutics reports fourth quarter and full year 2024 financial results and provides business update. News release. Werewolf Therapeutics. March 11, 2025. Accessed October 8, 2025. https://investors.werewolftx.com/news-releases/news-release-details/werewolf-therapeutics-reports-fourth-quarter-and-full-year-2024
- Dose escalation and expansion study of WTX-124 as monotherapy and in combination with pembrolizumab (pembro) in patients with selected advanced or metastatic solid tumors. ClinicalTrials.gov. Updated July 28, 2025. Accessed October 8, 2025. https://clinicaltrials.gov/study/NCT05479812
