A phase Ib/II study (SCORES) of durvalumab (D) plus danvatirsen (DAN; AZD9150) or AZD5069 (CX2i) in advanced solid malignancies and recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC): Updated results

Background: D activity may be enhanced by overcoming intratumoral immune suppression. DAN, an antisense oligonucleotide STAT3 inhibitor, and CX2i, a CXCR2 inhibitor, are being studied with D in patients (pts) with PD-L1 treatment naive/pretreated RM-HNSCC. Earlier data from this study suggested enhanced antitumor activity with DAN + D in these pts.1 Methods: Results from the dose escalation in solid tumor pts are as previously reported. The dose expansion evaluated objective response rate (ORR), duration of response (DOR), and correlative biomarkers in pts treated with second-line (2L) DAN 3 mg/kg QW + D 20 mg/kg or CX2i 40 mg BID + D 20 mg/kg in PD-L1 naive/pretreated pts, and with DAN or CX2i as monotherapies in PD-L1 naive pts. A new arm was added for first-line (1L) PD-L1 naive pts. We present biomarker, DOR and updated ORR data for DAN + D and CX2i + D in 2L PD-L1 naive pts. Results: At data cutoff (DCO) (21 Feb 2018) ORR for 2L PD-L1 naive pts receiving DAN + D was 26% (10/38; 95% CI 13.4%–43.1%) including 4 complete responses (CRs) and 6 partial responses (PRs) (7/10 pts in response are still ongoing at DCO); median DOR was not reached (NR) (range 5–70+ weeks). Responses were observed with DAN + D regardless of HPV status or PD-L1 expression. DAN + D's safety profile was consistent with previous reports; adverse events (AEs) including transaminase elevations and thrombocytopenia were manageable and reversible. Comparison of pre- and on-treatment biopsies showed drug uptake in immune cells and fibroblasts, reductions in a suppressive cell gene expression signature (GES), and increases in an IFNy GES. Additional biomarker data, pharmacokinetic data, and emerging data for DAN + D in 1L PD-L1 naive pts will be presented. By contrast, in PD-L1 naive pts treated with CX2i + D the ORR was 10% (2/20; 1 CR, 1 PR), the median DOR was NR (range 6.7–38.4+ weeks), and causally related AEs occurred in 76% of pts. Conclusions: These results suggest enhanced activity of DAN + D compared to CX2i + D or PD-L1 monotherapy in PD-L1 naive pts with RM-HNSCC and warrant further investigation. 1Cohen E, et al. Ann Oncol. 2017;28 (suppl 5):1135O. Clinical trial identification: NCT02499328. Editorial acknowledgement: Medical writing assistance was provided by Ann Yeung, CMPP, PhD, of Scientific Pathways, Inc. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: E.E.W. Cohen: Consultancy: Eisai, Pfizer, Merck, AstraZeneca, Bristol-Myers Squibb. K.J. Harrington: Consultancy, honoraria, speakers bureau, scientific advisory board memberships: Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, MSD, Pfizer; Research funding: AstraZeneca, MSD. D.S. Hong: Consultancy: Baxter, Bayer, Guidepoint Global, Janssen; Research funding: Adapitmmune, AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sanko, Eisai, Genentech, Genmab, Ignyta, Infinity, Kite Kyowa, Lilly, Loxo, Mirati, Merck, MedImmune, Molecular Template, Novartis, Pfizer, Takeda; Honoraria: Loxo, MiRNA; Ownership interest: Molecular Match (Advisor), Oncoresponse (Founder). R. Mesia: Speakers bureau: Merck, Bristol-Myers Squibb; Membership on any entity's board of directors or advisory committees: Merck, Bristol-Myers Squibb, MSD, Roche, AstraZeneca. M.L. Scott, P.D. Mitchell, G.M. Mugundu, P. McCoon, C.E. Cook, M. Mehta: Employment: AstraZeneca. U. Keilholz: Consultancy: AstraZeneca, Bayer, Bristol-Myers Squibb, Glycotope, MSD, Merck Serono, Novartis, Pfizer; Research funding: AstraZeneca, Bayer, Glycotope, Pfizer; Honoraria: AstraZeneca, Bayer, Bristol-Myers Squibb, Glycotope, MSD, Merck Serono, Novartis, Pfizer; Speakers bureau: AstraZeneca, Bayer, Bristol-Myers Squibb, Glycotope, MSD, Merck Serono, Novartis, Pfizer. All other authors have declared no conflicts of interest.