A phase II trial of pembrolizumab and cabozantinib in patients (pts) with recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC).

Nabil F. Saba Winship Cancer Institute Emory University School of Medicine, Atlanta, GA info_outline Nabil F. Saba, Asari Ekpenyong, Ashley McCook-Veal, Mihir Patel, Nicole Cherie Schmitt, William A. Stokes, James Edward Bates, Soumon Rudra, Marin Ibrahim Abousaud, Jameel Muzaffar, Kedar Kirtane, Yong Teng, Conor Ernst Steuer, Dong Moon Shin, Yuan Liu, Christine H. Chung

Authors Nabil F. Saba Winship Cancer Institute Emory University School of Medicine, Atlanta, GA info_outline Nabil F. Saba, Asari Ekpenyong, Ashley McCook-Veal, Mihir Patel, Nicole Cherie Schmitt, William A. Stokes, James Edward Bates, Soumon Rudra, Marin Ibrahim Abousaud, Jameel Muzaffar, Kedar Kirtane, Yong Teng, Conor Ernst Steuer, Dong Moon Shin, Yuan Liu, Christine H. Chung Organizations Winship Cancer Institute Emory University School of Medicine, Atlanta, GA, Emory University, Atlanta, GA, Winship Cancer Institute, Grayson, GA, Department of Otolaryngology Head and Neck Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, Emory University School of Medicine, Atlanta, GA, Head and Neck and Endocrine Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, H. Lee Moffitt Cancer Center, Tampa, FL, Winship Cancer Institute of Emory University, Atlanta, GA, Departments of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, Moffitt Cancer Center, Tampa, FL Abstract Disclosures Research Funding Pharmaceutical/Biotech Company exelixis. Background: Pembrolizumab (pembro) is an immune checkpoint inhibitor (ICI) approved for treating pts with recurrent/metastatic (RM) HNSCC. Cabozantinib (cabo) is a multiple receptor tyrosine kinase inhibitor (TKI) targeting MET and VEGFR2 shown to reduce tumor growth, metastasis, and angiogenesis and has immuno-modulatory properties. Methods: This is a phase II, open label multi-center, single arm trial evaluating the tolerability and clinical benefit of pembro administered at 200 mg every 3 weeks and cabo 40 mg daily for pts with RM HNSCC who have not received prior ICI. It had a lead-in safety cohort allowing reduction of cabo dose to 20mg daily. Eligible pts had RM HNSCC, deemed incurable, with a tumor PD-L1 CPS > 1, RECIST 1.1 measurable disease, a life expectancy of > 3 months, an Eastern Cooperative Group (ECOG) Performance Status (PS) of 0-1. Enrollment was initiated in March of 2019. We estimated that the ORR will improve to 35% with pembro+ cabo (from a historic of 18%) with a significance level of 0.05 and 80% power. Results: A total of 47 pts were screened, 13 screen failures [cavitation on scan (4), inability to swallow pills (2), other exclusions (7)]; 34 pts were enrolled, 32 were dosed and 31 evaluable (at least one follow-up scan). Pts had cancers of the oropharynx (21, 65%), nasopharynx (6, 19%), larynx/hypopharynx (4, 13%) and oral cavity (1,3%). 32 patients received cabo at 40 mg daily; 13 patients (41%) were dose reduced to 20mg daily [mucositis, increased liver function (LFT) tests, diarrhea]; males (n=29, 90%), median age 63 years (range 53-67); presence of distant metastases (34, 100%); prior radiation (29, 90%), chemotherapy (14, 43%); ECOG PS =0 (16, 50%), 1 (16,50%); HPV/p16 positive (17, 53%), negative (5, 16%), not applicable (10, 29%); the most frequent adverse event (AE) (all grades) was fatigue (16,50.0%), grade 3 or 4 treatment-related AE were increased LFTs, hyponatremia (3, 9.3% each). With a median follow up of 12.7 months (mos) (range 6.9- 20.5 mos), a RECIST 1.1 overall response rate ORR= 45.2% (CR=0; PR=14, 45.2%; SD =14, 45.2%; PD=3.0, 10%) with an overall clinical benefit of 90.4% were observed; The 1-yr OS was 67.7% (95% CI, 42.9%-83.6%; median 22.3 mos) and 1-yr PFS was 51.8% (95% CI, 28.8%-70.7%; median 14.6 mos). Conclusions: This phase II trial of pembro + cabo met its primary endpoint of ORR. The regimen is well-tolerated with very encouraging clinical activity in RM HNSCC and warrants further exploration in this disease. The study was supported by a grant from Exelixis to NFS. Clinical trial information: NCT03468218.