Background: In 78 BRAF V600E mut NSCLC pts, single agent D induced an overall response rate (ORR) of 32%. The combination of D and T (DT) has demonstrated significant improvements in efficacy compared with BRAFi monotherapy in BRAFV600 mut metastatic melanoma. Here, we report interim safety (33 pts) and efficacy (24 pts) data for NSCLC pts enrolled in this phase II DT study. Methods: This single-arm, 2-stage, phase II study was in advanced BRAFV600E mut NSCLC pts who failed at least 1 line of chemotherapy. D was dosed at 150 mg orally twice daily and T at 2 mg once daily. The primary endpoint was investigator-assessed ORR per RECIST 1.1 criteria. A minimum response rate ( ≥ 6 out of first 20 pts) was required to continue into the second stage. Results: Median age of 33 pts was 66 yrs (range 49–88 yrs). Most pts were female (64%), White (82%), former smokers (73%), and had adenocarcinoma (88%). Twenty-seven pts (82%) remain on therapy, and 6 have stopped (4 with disease progression, 2 due to adverse events [AEs]). Twenty-four pts were evaluable for efficacy (confirmed response). ORR was 63% (n = 15, partial responses; 95%CI 40.6%–81.2%), with responses being observed by the first scan (6 weeks) and disease control rate (DCR) for > 12 weeks was 88% (95% CI 67.6%–97.3%). Independent review response rates were consistent with investigator-assessed response. Most common ( > 20%) AEs were pyrexia, diarrhea, nausea, vomiting, decreased appetite, asthenia, cough, peripheral edema, and rash, mostly grade 1 or 2. Grade 3 AEs occurred in 39% of pts; most frequent were hyponatremia (6%), neutropenia (6%), and dehydration (6%). One pt (3%) had a grade 4 AE (hyponatremia) and 1 pt (3%) had a fatal serious AE of pleural effusion. AEs leading to a dose reduction were reported in 9 pts (27%). Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 2 pts (6%). Conclusions: DT in BRAF V600E mut advanced NSCLC pts shows early antitumor activity with an ORR of 63% and a manageable safety profile. The study met the criteria for progression to the second stage. Clinical trial information: NCT01336634