BACKGROUND: This phase 1, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), antitumor activity, and molecular correlates of @entity69383 , a Hedgehog pathway (HhP) inhibitor, combined with cetuximab in @entity1 with relapsed/metastatic @entity957 of the @entity135 . @entity1 AND METHODS: Cetuximab was given with a 400mg/m(2) loading dose followed by 250mg/m(2) weekly. @entity69383 was given daily starting two weeks after cetuximab initiation. A "3+3" study design was used. Prior therapy with cetuximab was allowed. @entity5 biopsies occurred prior to cetuximab initiation, prior to @entity69383 initiation, and after treatment with both drugs. RESULTS: Nine @entity1 were enrolled. The RP2D was 160mg, the same as the single-agent @entity69383 MTD. Among 9 treated, 8 evaluable @entity1 , the best responses were 1 partial response (12.5%), 4 stable disease (50%), and 3 disease progressions (37.5%). The median progression free survival was 77days (95% confidence interval 39-156). Decreases in @entity5 size were seen in both cetuximab-na  ve @entity1 (one HPV-positive, one HPV-negative). The most frequent treatment-emergent adverse events were @entity1295 , muscle cramps, and @entity1910 . No DLTs were observed. @entity5 shrinkage and progression free survival were associated with intra-tumoral @entity470 and HhP gene expression down-regulation during therapy, supporting the preclinical hypothesis. CONCLUSION: Treatment with @entity69383 and cetuximab yielded expected @entity137 with signs of anti- @entity5 activity. Serial @entity5 biopsies were feasible and revealed proof-of-concept biomarkers.

A pilot study of cetuximab and the hedgehog inhibitor XXXX in recurrent/metastatic head and neck squamous cell carcinoma.

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity135 :: ('MESH:D006258', 'Disease') :: ['head and neck'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity1910 :: ('MESH:D005076', 'Disease') :: ['rash'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Tumor'] @entity470 :: ('1956', 'Gene') :: ['ErbB'] @entity957 :: ('MESH:D002294', 'Disease') :: ['squamous cell carcinoma'] @entity1295 :: ('MESH:D005221', 'Disease') :: ['fatigue'] @entity69383 :: ('MESH:C541444', 'Chemical') :: ['IPI-926']
@entity69383 :: (MESH:C541444,Chemical) :: ['IPI-926']
