Royal Marsden Hospital/Institute of Cancer Research, London, United Kingdom
Kevin J. Harrington , Martin David Forster , Christophe Le Tourneau , Jose Ariza , Shuquan Chen , Jonathan Greenberg , Kenji Hirotani , Eva Remenar
Background: P, a fully human monoclonal antibody can block HER3 activation. HER3 activation is a resistance mechanism to C, induced by the ligand heregulin (HRG). This randomized phase 2 study in Europe evaluated first-line C + CIS or CAR + P or PBO for R/M SCCHN. Methods: Patients (pts) age ≥18 y with confirmed R/M SCCHN, stratified by HRG high vs low expression (via RT-PCR from tumor RNA) and human papilloma virus (HPV)+ vs HPV-, received IV P (18 mg/kg loading dose [LD]; 9 mg/kg maintenance dose [MD] every 3 weeks [q3w]) or PBO, and C (400 mg/m2 LD; 250 mg/m2 MD weekly) + ≤6 cycles of CIS (100 mg/m2 q3w) or CAR (AUC of 5). Co-primary endpoints were progression-free survival (PFS) in the intent-to-treat (ITT) and HRG high arms. Results: In all, 87 pts (44 P, 43 PBO; median age 59 y; 83% male) were treated; a median 6 (1-20) P cycles were completed. Pts received CAR (70%) or CIS (34%) (median 5 [2-6] CAR and 5 [1-6] CIS cycles) in the P arm and CAR (7%) or CIS (20%) (median 5 [1–6] cycles each) in the PBO arm. Discontinuations due to adverse events (AEs) were higher with P (16%) vs PBO (5%). Treatment-emergent AEs grade ≥3 were more frequent with P (84%) vs PBO (58%) (most frequent: acneiform dermatitis [14% vs 7%] and rash [14% vs 0%]). Serious AEs occurred in 43% (41% grade ≥3) (P) and 37% (33% grade ≥3) (PBO) of pts. In P and PBO arms, PFS and objective response rates (ORR; complete + partial response) in ITT, HRG-high (Table), HRG low (difference in PFS: HR 1.2, 95% CI 0.6–2.6, and ORR: 11.1%, 95% CI -15.8–36.0) and HPV- (difference in PFS: HR 1.5, 95% CI 0.9–2.7, and ORR: 4.7%, 95% CI -16.6–25.3) arms were similar (HPV+ arm was too small [n = 16] to draw meaningful results). Conclusions: P + C + CIS or CAR was not more effective than C + CIS or CAR. Clinical trial information: NCT02633800
PFS, mo, median (95% CI) P | PFS, mo, median (95% CI) PBO | PFS difference, HR (95% CI) P vs PBO | ORR, % (95% CI) P | ORR, % (95% CI) PBO | ORR difference, % (95% CI) P vs PBO | |
---|---|---|---|---|---|---|
ITT (N = 87) | n = 44 5.6 (4.1–6.5) | n = 43 5.5 (4.2–6.5) | 1.11 (0.7–1.9) P= 0.70 | n = 16/44 36.4 (22.8–52.3) | n = 12/43 27.9 (15.8–43.9) | 8.5 (-10.9–26.8) |
HRG high (n = 51) | n = 26 5.6 (4.1–7.1) | n = 25 5.6 (3.1–8.3) | 1.12 (0.6–2.3) P= 0.75 | n = 11/26 42.3 (24.0–62.8) | n = 9/25 36.0 (18.7–57.4) | 6.3 (-19.1–30.4) |
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