6000 Background: KEYNOTE-048 is a phase 3 study of P or P + chemo (C) vs EXTREME (E) as 1L therapy for R/M HNSCC (NCT02358031). At the second interim analysis (IA2), P significantly improved OS in the PD-L1 combined positive score (CPS) ≥20 and ≥1 populations and had noninferior OS in the total population with favorable safety; P+C significantly improved OS in the total population with comparable safety. We present the protocol-specified final results. Methods: 882 pts with locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting who provided a tumor sample for PD-L1 testing were randomized to P 200 mg Q3W for 24 mo (n = 301), P for 24 mo + 6 cycles of C (cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/d for 4 d Q3W) (n = 281), or E (cetuximab 400 mg/m2 loading/250 mg/m2 QW + 6 cycles of chemo) (n = 300). OS superiority was tested sequentially for P+C vs E in the CPS ≥20 population, then the CPS ≥1 population, and for P vs E in the total population (superiority thresholds: one-sided P = .0023, .0026, and .0059, respectively). Data cutoff was 25 Feb 2019 (~25 mo after last pt randomized). Results: P+C significantly improved OS vs E in the CPS ≥20 (HR 0.60, 95% CI 0.45-0.82, P = .0004; median 14.7 vs 11.0 mo) and CPS ≥1 (HR 0.65, 95% CI 0.53-0.80, P < .0001; median 13.6 vs 10.4 mo) populations. HR (95% CI) for PFS was 0.76 (0.58-1.01) for CPS ≥20 and 0.84 (0.69-1.02) for CPS ≥1. ORR (P+C vs E) was 42.9% vs 38.2% for CPS ≥20 and 36.4% vs 35.7% for CPS ≥1; median DOR was 7.1 vs 4.2 mo and 6.7 vs 4.3 mo, respectively. P did not significantly improve OS vs E in the total population (HR 0.83, 95% CI 0.70-0.99, P = .0199; median 11.5 vs 10.7 mo). HR (95% CI) for PFS was 1.29 (1.09-1.53). ORR (P vs E) was 16.9% vs 36.0%; median DOR was 22.6 vs 4.5 mo. All-cause gr 3-5 AE rates were 54.7% for P, 85.1% for P+C, and 83.3% for E. Conclusion: Overall, KEYNOTE-048 showed that compared with E, P+C had superior OS in the PD-L1 CPS ≥20, CPS ≥1, and total populations with comparable safety and P had superior OS in the CPS ≥20 and ≥1 populations, noninferior OS in the total population, and favorable safety. These results support pembrolizumab and pembrolizumab + platinum + 5-FU as new 1L standards of care for R/M HNSCC. Clinical trial information: NCT02358031.

9008 Background: ALK tyrosine kinase inhibitors (TKIs) are standard of care for patients (pts) with advanced ALK+ NSCLC, and preclinical data suggest potential synergistic activity with checkpoint inhibitors in NSCLC irrespective of ALK status. Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody approved in various countries for treatment of metastatic Merkel cell carcinoma, and in the US for advanced urothelial carcinoma that has progressed following platinum therapy. We report initial results from JAVELIN Lung 101 (NCT02584634), a phase 1b/2 dose-finding trial of avelumab + crizotinib (A+C) or the next-generation ALK TKI lorlatinib (A+L) in pts with advanced/metastatic ALK-negative/wildtype (ALK−) or ALK+ NSCLC, respectively. Methods: In phase 1b, pts with previously treated ALK− NSCLC received A (10 mg/kg Q2W) + C (250 mg BID) while pts with ALK+ NSCLC received A (10 mg/kg Q2W) + L (100 mg QD) (starting dose levels in each group). The primary endpoint was dose-limiting toxicities (DLTs); secondary endpoints included adverse events (AEs) and objective responses. Results: At data cutoff on Oct 27, 2017, 12 ALK− pts had received A+C and 28 ALK+ pts had received A+L. All ALK− pts had received prior anticancer therapy; ALK+ pts had received a median 2 prior ALK TKIs (range 1-3; data not reported for 1 ALK+ pt). DLTs occurred with A+C in 5 ALK− pts (41.7%): ALT and AST increase (2 pts each), febrile neutropenia, hepatitis, QT prolongation, and rash (1 pt each). No DLTs occurred with A+L in ALK+ pts. Grade ≥3 AEs of any causality occurred with A+C in 7 ALK− pts (58.3%; most common [≥10%] was ALT increase [16.7%, n = 2]), and with A+L in 15 ALK+ pts (53.6%; most common were hypertriglyceridemia [14.3%, n = 4] and GGT increase [10.7%, n = 3]). The confirmed objective response rate with A+C in ALK− pts was 16.7% (95% CI, 2.1-48.4; partial response [PR] in 2 pts), and with A+L in ALK+ pts was 46.4% (95% CI, 27.5-66.1; PR in 12 pts; complete response in 1 pt). Conclusions: A+L showed an acceptable safety profile, distinct from A+C, and promising antitumor activity in pts with ALK+ NSCLC, and will be evaluated in treatment-naive pts in phase 2. Clinical trial information: NCT02584634.

10018 Background: Cemiplimab monotherapy achieves clinically meaningful activity in pts with advanced CSCC (metastatic [mCSCC] or locally advanced [laCSCC] not amenable to curative surgery or curative radiation) and has a safety profile consistent with other anti–PD-1 agents. Based on initial data (median follow-up of 9.4 months in the pivotal study, NCT02760498), cemiplimab (cemiplimab-rwlc in the US) was approved for the treatment of pts with advanced CSCC. Historical data shows median overall survival (OS) of approximately 15 months with conventional chemotherapy or EGFR inhibitors (ASCO 2019, e21033). We present ~1-year additional follow-up from the largest prospective data set in advanced CSCC. Methods: Pts received cemiplimab 3 mg/kg Q2W (Group [Gp] 1; mCSCC; Gp 2, laCSCC) or cemiplimab 350 mg Q3W (Gp 3, mCSCC). The primary endpoint was objective response rate (ORR; complete response + partial response) per independent central review (ICR). Data presented here are per investigator review (INV); ICR data will be available at the meeting. Results: 193 pts were enrolled (Gp 1, n = 59; Gp 2, n = 78; Gp 3, n = 56). 128 pts had received no prior anti-cancer systemic therapy, 65 pts were previously treated. As of Oct 11, 2019 (data cut-off), median duration of follow-up was 15.7 months (range: 0.6–36.1) among all pts; 18.5 months (range: 1.1–36.1) for Gp 1, 15.5 months (range: 0.8–35.0) for Gp 2, and 17.3 months (range: 0.6–26.3) for Gp 3. ORR per INV was 54.4% (95% CI: 47.1–61.6) for all pts; 50.8% (95% CI: 37.5–64.1) for Gp 1, 56.4% (95% CI: 44.7–67.6) for Gp 2, and 55.4% (95% CI: 41.5–68.7) for Gp 3. ORR per INV was 57.8% (95% CI: 48.8–66.5) among treatment-naïve pts and 47.7% (95% CI: 35.1–60.5) among previously treated pts. Median duration of response (DOR) has not been reached (observed DOR range: 1.8–34.2 months). In responding pts, estimated proportion of pts with ongoing response at 24 months was 76.0% (95% CI: 64.1–84.4). Median OS has not been reached. Estimated OS at 24 months was 73.3% (95% CI: 66.1–79.2). The most common treatment-emergent adverse events (TEAEs) by any grade were fatigue (34.7%), diarrhea (27.5%), and nausea (23.8%). The most common grade ≥3 TEAEs were hypertension (4.7%) and anemia and cellulitis (each 4.1%). Conclusions: For pts with advanced CSCC, cemiplimab achieves ORRs, DOR and survival superior to what has been reported with other agents. Clinical trial information: NCT02760498.