Hoth Therapeutics ends its HT-001 Phase 2a trial early following positive interim findings and plans FDA discussions on potential Phase 3 development.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Rocket One Inc. has announced that its biotechnology subsidiary, Hoth Therapeutics, has decided to conclude its Phase 2a clinical trial of HT-001 earlier than planned following positive interim efficacy findings. The company plans to seek feedback from the U.S. Food and Drug Administration (FDA) on advancing the investigational treatment into a potential Phase 3 programme.
HT-001 is an investigational topical formulation of aprepitant, a neurokinin-1 (NK1) receptor antagonist, being developed to manage dermatologic toxicities associated with epidermal growth factor receptor (EGFR) inhibitor cancer therapies. These complications, including acneiform rash, itching and skin irritation, can affect patients’ quality of life and potentially interfere with the continuation of anticancer treatment.
According to the November 3, 2026 announcement, Hoth’s decision followed a review of interim efficacy and safety data. Although the company described the findings as strong, it has not disclosed numerical results, detailed safety observations or the number of patients included in the latest interim analysis.
HT-001: Investigating a Topical Approach to EGFR Inhibitor-Associated Skin Toxicities
EGFR inhibitors are used to treat several cancers, including lung and colorectal cancers. However, inhibition of EGFR signalling can also affect normal skin cells, resulting in adverse effects such as acneiform rash, dryness, itching and nail disorders.
These complications may require additional supportive care and, in some cases, lead to dose modifications or interruptions of cancer treatment.
HT-001 is designed to deliver aprepitant directly to affected skin areas through a topical formulation. Its development focuses on managing treatment-associated dermatologic symptoms through localized drug delivery.
CLEER-001 Phase 2a Trial: Study Design and Clinical Findings
HT-001 is being evaluated in CLEER-001 (NCT05639933), a multicenter, randomized, double-blind, placebo-controlled Phase 2a dose-ranging study.
The trial comprises two parts:
- Part 1: An open-label pharmacokinetic cohort involving 12 patients receiving HT-001 2% topical gel.
- Part 2: A randomized, double-blind cohort evaluating HT-001 concentrations of 0.5%, 1% and 2% against placebo.
The randomized treatment groups follow a 2:2:2:1 allocation ratio. Participants apply the study gel once daily to affected areas, including the skin, scalp and nails, for six weeks. Treatment is permitted for cutaneous toxicity involving up to 30% of body surface area.
The primary efficacy assessment uses the Acneiform Rash Investigator Global Assessment (ARIGA) scale, alongside assessments of safety, tolerability, skin symptoms, pain, itching and quality of life. The study was designed to identify the minimum efficacious dose strength for further investigation.
Hoth has previously reported encouraging clinical observations from the programme. In April 2025, the company reported a 50% reduction in mean pruritus scores, from 1.6 at baseline to 0.8 by Day 21, in the open-label cohort. In June 2025, it reported that all enrolled patients in this cohort achieved at least one measure of clinical dermatologic improvement, while more than 65% experienced reductions in pain and itching.
In April 2026, Hoth reported that an interim analysis had met its primary efficacy endpoint, with patients reaching an ARIGA score of 1 or below by Week 6. The company also reported reductions in pain and itching in more than 65% of patients and no dose reductions or discontinuations of EGFR inhibitor therapy during HT-001 treatment.
These findings provide context for the programme’s development. However, they were company-reported observations, and the available announcements do not provide sufficient patient-level or statistical information to independently establish the magnitude of treatment benefit.
Early Trial Conclusion and Potential Phase 3 Development
Following its latest review of interim efficacy and safety data, Hoth determined that the findings supported concluding the Phase 2a study earlier than originally planned.
The November announcement does not provide detailed results from this latest analysis, including response rates, statistical significance, treatment-group comparisons or adverse-event findings. Consequently, the incremental clinical benefit and overall safety profile cannot yet be fully assessed.
Hoth plans to complete the remaining data review and analysis before pursuing regulatory discussions with the FDA. These discussions are expected to address the design of a potential pivotal study, efficacy endpoints, target patient population, statistical considerations, safety requirements and manufacturing readiness.
Importantly, the decision to conclude Phase 2a does not establish that Phase 3 has been approved or initiated. Further development will depend on regulatory feedback and completion of the necessary activities.
Clinical Significance
HT-001 addresses an important supportive-care need in oncology, where dermatologic toxicities can affect treatment tolerability and patient quality of life. Its topical aprepitant formulation represents an investigational approach to managing these complications through localized drug delivery.
Previously reported findings, including improvements in rash severity and patient-reported symptoms, provide an encouraging clinical signal. However, the absence of detailed results from the latest interim analysis limits assessment of the treatment’s efficacy and safety, particularly against placebo.
The next development milestone will be the company’s regulatory discussions with the FDA. The outcome will help establish whether the available evidence supports a pivotal Phase 3 programme and what additional clinical data will be required.
HT-001 remains investigational and has not received FDA approval for any indication.
References
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, Rocket One, 03 November 2026
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 (CLEER), ClinicalTrials.gov ID NCT05639933
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.