KX2-391 Ointment 1%, a novel dual sarcome (Src)/tubulin inhibitor, was shown to be efficacious in the treatment of adults with actinic keratosis (AK) in two phase 3 studies (KX01-AK-003 and KX01-AK-004). Primary outcome measures for the study consisted of 100% AK clearance, or partial clearance specific to the face or scalp. KX2-391 Ointment 1% demonstrated statistically significant clinical benefit over placebo, with 44% of KX01-AK-003 patients and 54% of KX01-AK-004 patients reporting 100% AK clearance. Outcome measures for safety metrics demonstrated that treatment-related emergent adverse events (TEAEs) were mild-to-moderate.

To assess the primary efficacy endpoint of 100% clearance of AK at day 57, and to assess the safety, local skin reactions (LSRs) and adverse events (AEs) of KX2-391 ointment 1% versus vehicle in adults with AK.

Type of Study

• Double-blind.
• Vehicle-controlled.
• Randomized.
• Parallel group.
• Multicenter.
• Phase 3.

Primary Purpose

• Assessment of primary efficacy endpoint of 100% clearance of AK at day 57 for KX2-391 ointment 1% versus vehicle in adults with AK.
• Assessment of the safety (local skin reaction and (AEs) of KX2-391 ointment 1% versus vehicle in adults with AK.

Patient Populations

• Total number of enrollees: 702 subjects in two identical studies, comprising 351 patients each located at 31 sites per study.
• Intent-to-treat population.
• Median Age: 69.75 years.
• Sex: Male/Female ratio of 6.7 to 1.
• Race: 99.5% white.
• Fitzpatrick skin type I/II composition: 72.75%.
• Median baseline AK lesion count: 6.
• Treatment area: Face to Scalp ratio: 2:1

Primary Outcome Measures

• The primary outcome measure was 100% clearance of AK at day 57 within the 25cm² area in adult AK patients using KX2-391 ointment 1% versus vehicle.

Secondary Outcome Measures

• Assessment of safety data specific to local skin reaction and AEs of KX2-391 ointment 1% versus vehicle in adults with AK.

Drugs/Procedures Used

• KX2-391 is a small molecule with differentiated mechanisms of action, including inhibition of Src kinase activity and inhibition of tubulin polymerization that leads to an upregulation of apoptosis in proliferating cells.
• The treatment area was 25 cm² with 4-8 typical visible AK lesions on face or scalp.
• KX2-391 ointment 1% vs. vehicle at 1:1 ratio.
• Treatment occurred once daily for 5 consecutive days, applied by study participants and left in place for approximately 12 hours.
• Treatment compliance greater than 99% was achieved.

• Outcome measures for efficacy demonstrated a statistically significant effect from KX2-391 treatment versus vehicle (Table).
• Outcome measures for safety demonstrated that KX2-391 was well tolerated.
• No ocular exposure led to ocular adverse events.
• There were no related clinically significant abnormal EKGs, changes in physical exams, or, vital signs, or laboratory findings.
• All serious adverse events (SAEs) that occurred during the study were considered unrelated to the treatment.
• The proportion of TEAEs were 11-20% in the active group versus 9-11% in the vehicle only group.
• The mean composite LSR sum of 4 occurred at day 8 and resolved on average by day 29, with the most common LSR occurrences consisting of erythema, flaking or scaling.

• KX2-391 ointment 1% was shown safe and effective in two identical phase 3 trials, demonstrating higher overall complete AK clearance rates at day 57, with 44% and 54% of patients achieving 100% AK clearance.
• Clinical differences were demonstrated to be statistically significant for all subgroups analyzed, including scalp and face.
• Most TEAEs consisted of application site pruritus or pain that was mild-to-moderate and required no treatment.
• Study participant compliance was excellent, with > 99% completing the full 5-day self-application of ointment.