HT-001 Trial Ended Early, Phase 3 Planned for EGFR Inhibitor Rash Management

The phase 2a CLEER-001 trial (NCT05639933) of HT-001 will terminate earlier than planned after a review of interim efficacy and safety data. The sponsor, Hoth Therapeutics, plans to request FDA feedback on a potential phase 3 program, according to a news release.¹

HT-001, which delivers the neurokinin-1 receptor antagonist aprepitant directly to the skin, is in development for dermatologic toxicities associated with EGFR inhibitor therapy.

Hoth Therapeutics cautioned that the interim findings are preliminary and could shift once data collection is complete, and said it still needs to finish analyzing the data before submitting them to the FDA.

“We are encouraged by the strength of the interim findings and believe they support taking the next step toward a potential phase 3 program,” said Robb Knie, CEO of Rocket One, Hoth Therapeutics’ parent company, in the news release.¹

Trial Design

EFGR inhibitors are associated with skin toxicities in up to 90% of patients, including rash, pruritus, dryness, nail changes, and alopecia. CLEER-001 is a multicenter, dose-ranging phase 2a study in adults receiving a variety of approved EGFR inhibitors who have skin toxicity at 12 sites in the United States, Poland, and Spain. The trial includes an open-label pharmacokinetic cohort of patients treated with HT-001 2% topical gel and a randomized, double-blind, placebo-controlled portion in which patients were to be assigned 2:2:2:1 to HT-001 2%, 1%, or 0.5% gel or vehicle.

Eligible patients had developed a rash or symptoms of rash (papular and/or pustular eruptions or cutaneous burning) with overall involvement of 30% or less body surface area (BSA). Patients who had grade 4 skin toxicity or BSA involvement of over 30%, or other grade 3 or higher EGFR-related toxicity were ineligible. Patients were also excluded if they had a history of other skin disorders that could confound results.

The primary efficacy end point is response of acneiform rash on the Acneiform Rash Investigator’s Global Assessment scale, and estimated enrollment was 152 patients.² Among the secondary end points is the proportion of patients who required dose reduction or discontinuation of EGFR inhibitor during the 6-week period. The estimated primary completion date of the study was December 30, 2026.

Previously Reported Data

In June 2025, Hoth reported interim results from the open-label cohort, in which all enrolled patients met at least 1 primary end point of clinical dermatologic improvement and more than 65% reported reductions in pain and pruritus. No patients required a dose reduction or discontinuation of EGFR inhibitor therapy, and no serious adverse events were reported. The company did not report the number of patients in that analysis.³ ClinicalTrials.gov lists the open-label cohort as 12 patients.²

The FDA accepted the investigational new drug application for HT-001 in December 2022. The company is developing HT-001 under the 505(b)(2) regulatory pathway, which allows it to rely on existing safety data for aprepitant.³

Next Steps

Hoth intends to seek FDA input on the design of a potential pivotal study, covering the choice of efficacy end points and population, the statistical approach, safety requirements, and manufacturing. Starting a phase 3 trial will depend on that feedback and on completing other required development activities, according to the company.¹

“We believe these findings warrant a focused discussion with the FDA about how to evaluate HT-001 in a larger study and generate the evidence needed to support a potential registration pathway,” Knie stated.¹

REFERENCES

1. Rocket One’s Hoth Therapeutics reports strong HT-001 efficacy results, ends phase 2a early and plans to pursue phase 3 to bring treatment to cancer patients. News release. Rocket One Inc. November 3, 2026. Accessed November 3, 2026. https://tinyurl.com/2sw66sec

2. Study to investigate the efficacy, safety, and tolerability of topical HT-001 for the treatment of skin toxicities associated with epidermal growth factor receptor inhibitors. ClinicalTrials.gov. Updated March 31, 2026. Accessed November 3, 2026. https://clinicaltrials.gov/study/NCT05639933

3. Hoth Therapeutics HT-001 interim results first-in-class topical therapy preserves cancer treatment while resolving dermatologic side effects. News release. Hoth Therapeutics. June 24, 2025. Accessed November 3, 2026. https://tinyurl.com/4ersj9pe