Anti–PD-1 immunotherapy with chemotherapy for poorly chemo-responsive thyroid and salivary gland tumors: The iPRIME study.

6124 Background: Clinical trial data guiding treatment of unresectable or metastatic salivary and thyroid gland cancers are limited. While targeted therapies have advanced management for selected patients, chemotherapy remains a treatment strategy for those with aggressive disease biology. Anti-PD1 therapy has shown antitumor activity in advanced, PD-L1 positive salivary and thyroid gland cancers, underscoring the need to evaluate the synergistic activity of PD-1 blockade with cytotoxic chemotherapies in these neoplasms. Methods: The iPRIME (NCT03360890) is a single center, parallel two cohort trial evaluating pembrolizumab with cytotoxic chemotherapy in patients with advanced salivary gland and thyroid cancers. Eligible patients had histologically confirmed disease that was unresectable and not amenable to curative intent therapy. Patients received pembrolizumab 200 mg IV with docetaxel or doxorubicin 75 mg/m2 for 2-6 cycles, followed by pembrolizumab monotherapy for up to 2 years. Docetaxel or doxorubicin could be reintroduced upon disease progression while on pembrolizumab or after the 2-year treatment period. The primary endpoint was response rate. Secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate, and adverse events. Results: A total of 39 patients (27 salivary and 12 thyroid cancer) were enrolled between 2018-2022. Mean age was 61 in salivary and 71 in the thyroid cancer, with 48% and 58% female patients, respectively. Salivary gland cancer histologies included adenoid cystic 15/27 (56%), ex-pleomorphic 18%, mucoepidermoid 7.4%, acinic cell 7.4%, salivary duct 7.4%, basaloid adenocarcinoma 3.7%. In the salivary gland group, the overall response rate was 25.6% (7/27; 90% CI 12.9%-43.2%), and the disease control rate was 89% (24/27; 90% CI 73.7%-96.9%). The overall response rate in the adenoid cystic patients was 27% (4/15). Median PFS was 8.6 months (90% CI: 6.0 to 12.4), including 8 months in adenoid cystic patients (90% CI: 6.0-16.7%) and 7.8 months in the non-adenoid cystic cases (90% CI: 3.8-14.6), with one and two-year PFS rates of 37% and 8.2%, respectively. Median OS was 25.5 months in the adenoid group (90% CI:8.5-32) and 22.9 months in the non-adenoid group (90% CI: 7.8-78) (p=0.26). One, two, and five-year OS rates in the salivary cohort were 66%, 50%, and 23%, respectively. In the thyroid cohort, the response rate was 16.7% (2/12), with both PR. Grade 4 events occurred in nine patients salivary patients and one grade 5 event was observed. Conclusions: The combination of pembrolizumab and cytotoxic chemotherapy did not substantially change antitumor control activity relative to historical controls in patients with advanced salivary or thyroid cancers. There were no statistically significant differences in PFS and OS between adenoid cystic and non-adenoid cystic subtypes. Clinical trial information: NCT03360890 .