Background: Salivary gland cancers comprise <1% of cancers. Advanced cases have a 40% 5-year survival rate. Due to their rarity, no standard treatment guidelines exist. However, salivary duct carcinomas have morphological and gene expression profiles similar to breast cancers, and 20–40% of this subset have HER2 alterations. MyPathway (NCT02091141) is an ongoing, phase 2, multi-basket study evaluating the efficacy of targeted treatments in nonindicated tumor types with alterations in the HER2, BRAF, Hedgehog (Hh), or EGFR pathways. We present interim data for patients with salivary cancer. Methods: Patients had advanced salivary cancer with HER2 (amplification, overexpression, and/or mutation) or Hh (SMO or PTCH-1) alterations, locally assessed by gene sequencing, FISH, or IHC, as applicable. Patients received standard doses of pertuzumab + trastuzumab or vismodegib, respectively, until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed objective response rate (ORR) by RECIST v1.1. Results: As of Nov 30, 2016, 8 patients had been treated for salivary cancer, all carcinomas (7 had HER2 alterations; 1 had an Hh alteration). One HER2 patient without a post-baseline tumor assessment by data cut-off was not evaluable for efficacy. Characteristics and outcomes are shown (Table). Of 6 patients with a complete response (CR) or partial response (PR), 5 patients were still receiving study treatment by the data cut-off, with a median time on treatment of 4.6 months (range 1.4–12.5). There were no new safety signals. Conclusions: Six of 7 patients (86%) with advanced salivary carcinoma achieved CR or PR by targeting HER2 (n=5) or Hh (n=1) alterations. These promising results merit study of these treatments in additional patients. Accrual to MyPathway is ongoing. Clinical trial information: NCT02091141

^aSix patients had HER2 amplification/overexpression (1 patient with PR also had HER2 mutations [D769H/L755F]). The unevaluable patient had a HER2 mutation (S310F); ^bPTCH-1 (Q400*); ^cCR + PR; ^dIn 6 evaluable patients.