Cdx3379-04: Phase Ii Evaluation Of Cdx-3379 In Combination With Cetuximab In Patients With Advanced Head And Neck Squamous Cell Carcinoma (Hnscc).

6025 Background: CDX-3379, an anti-ErbB3 monoclonal antibody with a half-life-extending YTE modification in its Fc region, binds a unique epitope that locks ErbB3 in an inactive form and inhibits ErbB3 signaling, the latter implicated in tumor growth/resistance to anticancer therapies. CDX-3379 enhances antitumor activity of targeted therapies in preclinical models. In a Phase 1 clinical study, CDX-3379 was well-tolerated alone and in combination with cetuximab. A durable complete response (CR) to CDX-3379 + cetuximab was observed (8.3 months) in a patient (pt) with cetuximab-refractory HNSCC (Falchook ASCO 2016). Methods: This open-label phase 2 study (NCT03254927) was designed to enroll up to 30 pts with advanced, HPV-, HNSCC, previously treated with cisplatin, anti-PD-1 antibodies, and cetuximab-resistant (progression within 6 months), according to a Simon’s 2-stage design (13 evaluable pts in Stage 1 with ≥1 objective response allows enrollment of 14 more pts in 2nd stage). Pts receive CDX-3379 (initial dose 12 mg/kg IV every 21 days) + cetuximab (loading dose 400 mg/m2; 250 mg/m2 IV weekly) until disease progression/toxicity. Endpoints include objective response rate (primary), progression-free and overall survival, safety, pharmacokinetics, immunogenicity, and exploratory biomarkers. Results: Stage 1 accrual is complete with 14 evaluable pts treated. All pts were heavily pretreated; prior therapies included surgery (10/14) and chemotherapy (13/14). All pts had prior radiation, cetuximab and PD-1 targeted therapy. One confirmed ongoing CR (8.1+ months) was observed. 7/14 pts experienced stable disease (SD), including 4 with tumor shrinkage (8-27.5% reduction). Three pts continue treatment. Treatment-related adverse events were generally grade 1-2 and included diarrhea (53%), hypokalemia (20%), prolonged QT interval (13%) and rash (13%). Conclusions: CDX-3379 in combination with cetuximab is well tolerated with the primary toxicity of diarrhea. Signs of antitumor activity were observed in these cetuximab-resistant HNSCC pts, including an ongoing, durable CR. Complete stage 1 results will be presented. Clinical trial information: NCT03254927.