Neoadjuvant Pembrolizumab Yields High pCR Rate in Desmoplastic Melanoma

Neoadjuvant treatment with pembrolizumab (Keytruda) significantly reduced or eliminated tumors in patients with desmoplastic melanoma and led to high pathological complete response (pCR) rates, according to results from the phase 2 SWOG S1512 trial (NCT02775851) published in Nature Cancer.

Main Data from the SWOG S1512 Trial

The results from this readout were from cohort A of the trial. The primary efficacy analysis for the neoadjuvant cohort revealed that 71% (95% CI, 51%-87%; P <.001) of patients achieved a pCR. These results met the primary end point.

The secondary end point of clinical response defined by RECIST v1.1 criteria was assessed using radiographic measurements from imaging scans or clinical measurements by documented photographs. At baseline, 3 patients did not have measurable disease, which left 25 patients to be assessed.

At the clinical response assessment time of 9 weeks, 16% of patients had a complete response, and 32% had a partial response. This showed an overall clinical response rate of 48% (95% CI, 28%-69%). Additionally, 36% of patients had stable disease, and 4% showed disease progression.

Long-term outcomes remained favorable at a median follow-up of 42 months (95% CI, 35-50). The 3-year relapse-free survival (RFS) rate was 74% (95% CI, 51%-87%), and the median value was not yet reached. Among patients in the neoadjuvant group, the 3-year overall survival (OS) rate was 87% (95% CI, 65%-96%). The melanoma-specific survival rate was 95% (95% CI, 80%-100%). Four deaths were noted, with 3 having unrelated causes and 1 with an unknown cause.

“[C]ohort A of S1512 demonstrates a high rate of pCR in patients with resectable desmoplastic melanoma receiving neoadjuvant infusions of pembrolizumab, with generally manageable toxicities and excellent long-term outcomes, with none of the patients in this series having been reported to die from melanoma or [adverse] effects [AEs] of the treatment,” lead study author Kari Kendra, MD, PhD, from Ohio State University Wexner Medical Center, wrote with coauthors in the publication.

Surgical Outcomes

Of the 27 patients evaluated for surgery, 93% underwent wide excision of resectable disease, 69% underwent sentinel lymph node biopsy, and 8% underwent a lymph node dissection. Additionally, 4% of patients underwent surgical resection of a nodal recurrence without wide excision of the primary skins site, with the lymph node being the only site of disease. To obtain clear margins, 2 patients had subsequent surgical resections. For the 5 patients with lymph node involvement at baseline, all underwent lymphadenectomies after neoadjuvant pembrolizumab.

Trial Details

The trial enrolled 28 evaluable patients who were given intravenous pembrolizumab at 200 mg every 3 weeks followed by excision. The median age of patients was 75 years (range, 37-91), 75% were male, and 96% were White. The most common primary tumor location was the head and neck (68%). Additionally, 79% of patients had an ECOG performance status of 0, 82% had primary disease status, and 89% had normal lactate dehydrogenase at baseline.

The primary end point of the trial was the pCR rate, measured as the percentage of patients with no viable tumor cells present in the surgical specimen following neoadjuvant pembrolizumab. Secondary end points included the clinical response rate, OS, RFS, and safety.

Safety

Treatment-related AEs (TRAEs) were noted in 79% of patients. Those that were the most common included fatigue (43%), maculopapular rash (21%), and diarrhea (14%). Grade 3 AEs were noted in 7% of patients. These patients had mucositis or immune-mediated colitis, which led to discontinuation. However, both patients were able to undergo surgical resection.

References

Kendra KL, Bellasea SL, Eroglu Z, et al. Neoadjuvant PD-1 blockade in surgically resectable desmoplastic melanoma: cohort A of the phase 2 SWOG S1512 trial. Nat Cancer. Published online January 29, 2026. doi:10.1038/s43018-025-01113-y