Background: MF, the most common form of cutaneous T-cell lymphoma, is characterized by infiltration of the skin by malignant T cells and can further progress to other organs. Early stage disease (limited/localized skin involvement) is managed with skin-directed therapies. The first FDA approved topical formulation of MCH, MCH 0.02% gel (equivalent to 0.016% w/w MCH, mechlorethamine) was noninferior to MCH-Aquaphor (AP) 0.02% in a 12 mo study (Study 201). In clinical practice, patients (pts) who tolerate MCH 0.02% without complete response (CR) may have their dose increased to maximize response. Study 202 tested the efficacy and safety of MCH 0.04% gel after MCH 0.02%. Methods: Pts eligible for this 7 mo phase 2 extension study completed 12 mos of treatment with MCH 0.02% gel or AP without CR. All pts applied a thin layer of MCH 0.04% gel once daily. Application frequency could be reduced for toxicity. Primary endpoint was response rate defined as ≥ 50% improvement in composite assessment of index lesions score (CAILS) of up to 5 lesions, confirmed ≥ 4 weeks later. Results: 98 of 100 enrolled pts were treated in Study 202 (MCH 0.04%); 86.7% completed the trial. 26 pts (26.5% [18.6-35.9]) achieved confirmed CAILS response from Study 202 baseline, including 6 CR. Additionally, 14 pts (14.3%) had their first response at final visit—unconfirmed response rate, 40.8% (31.5-50.7). There was no difference in response by age, race, or gender. CAILS response rates were also assessed from Study 201 (MCH 0.02%) baseline for index lesions identified at the start of that trial, with confirmed responses occurring in 74 pts (75.5% [66.3-83.2]). By week 88, 33 pts (84.4%) who had previously received MCH 0.02% gel and 39 pts (67.9%) who had previously received MCH 0.02% AP in Study 201 had responses over the course of these sequential studies. Drug related skin adverse events in Study 202 were mostly mild to moderate and were reported by 31 pts (31.6%); the most common were skin irritation (11.2%), erythema (10.2%), and pruritus (6.1%). Conclusions: Pts with stage I or IIA MF who did not achieve CR after 12 mos of daily topical MCH 0.02% had additional clinical benefit with up to 7 mos of treatment with MCH 0.04% gel, which was well tolerated in these pts. Clinical trial information: NCT00535470.