"Rare" Successes at AACR 2023

S1512: Outstanding Response Rate in Desmoplastic Melanoma
At last year’s ASCO meeting, Dr. Kari Kendra presented impressive results from the first cohort of patients enrolled to the S1512 clinical trial in rare desmoplastic melanoma. At the clinical trials plenary session at AACR last Sunday, she presented even more impressive results from the second cohort of patients on S1512.

These Cohort B patients all had unresectable desmoplastic melanoma and were treated with the PD-1 inhibitor pembrolizumab. Of the 27 patients treated, 24 saw their disease respond to the immunotherapy – 15 with a partial response, nine with a complete response. This 89 percent response rate to single-agent immunotherapy is all but unprecedented. 

It’s visually impressive as well. Here’s some beautiful waterfall scenery from Dr. Kendra’s AACR presentation on the S1512 Cohort B results.

The practice-changing takeaway is that patients with unresectable metastatic desmoplastic melanoma are likely to be exceptional responders to single-agent PD-1 blockade therapy with pembrolizumab.

S1609: DART Successes in Rare Gynecologic Cancers
The landmark DART trial (Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors), which treated a wide range of rare cancers with the immunotherapy combination of ipilimumab and nivolumab, has reported a number of notable successes over the years – in metaplastic breast cancer, neuroendocrine tumors, and angiosarcoma. The DART team can now add some notable responses in rare gynecologic cancers to that list.

At AACR, Dr. Young Kwang Chae reported on DART results in five cohorts of patients with gynecologic cancers. Three of those cohorts included patients whose disease showed durable responses to the treatment. Several of these patients remain in remission more than three years after starting immunotherapy.

In a cohort of 19 patients with clear cell ovarian cancer, three patients had disease that showed a complete response to treatment. Two of these patients remain in remission after more than three years.

Among a group of five patients with small cell ovarian cancer, hypercalcemic type, the disease showed a complete response to the immunotherapy combination in one patient and a partial response in a second patient. The first of these patients has now been in remission for about three years.

Finally, in the cohort of patients with non-epithelial ovarian cancer, four of the eight patients who had granulosa cell subtype experienced stable disease or better for at least six months while on immunotherapy.

The numbers of patients are small, as is usually the case with clinical trials in rare (and ultra-rare) cancers, but in some cases, these are the first reports of a treatment having a meaningful impact, and the results may also help identify key subtypes to target in future research.

DART was the first federally funded immunotherapy trial in rare cancers. It recently closed after more than six years, during which time it enrolled about 800 patients with dozens of types of rare cancers, and it has amassed a treasure trove of clinical data and tissue specimens from uncommon tumor types. It regularly reports important results in rare malignancies, and I expect it will continue to do so for years to come!