Abstract 1270P
Background
Atezolizumab (atezo, anti–PD-L1) is indicated for intravenous (IV) use in NSCLC, SCLC, TNBC, and UC. A novel, subcutaneous (SC) formulation of atezo with recombinant human hyaluronidase (rHuPH20), a permeation enhancer for SC dispersion and absorption, is being developed to reduce treatment burden and improve health care efficiency.
Methods
In this phase Ib dose-finding study (Part 1 of IMscin001), patients (pts) with advanced/metastatic NSCLC previously treated with chemotherapy (no prior cancer immunotherapy) were enrolled in 3 cohorts to receive atezo SC: 1) 1800 mg (thigh) single dose × 1 cycle; 2) 1200 mg (thigh) every 2 weeks (q2w) × 3 cycles; 3) 1800 mg (abdomen × 1, and then thigh × 2) every 3 weeks (q3w); then all cohorts received atezo IV 1200 mg q3w for each subsequent cycle until disease progression. Main objectives were to evaluate pharmacokinetics (PK) and safety of atezo SC.
Results
A total of 67 pts were enrolled. Baseline demographics were balanced, and safety was comparable across cohorts. Mean age was 64.2 years (range: 31-83), 61.2% were male, 65.7% were ECOG PS1. Atezo SC (1800 mg q3w, 1200 mg q2w) provided similar Cycle 1 Ctrough and AUC values as atezo IV (ref, 1200 mg and 840 mg, respectively; Table). Overall, 57 pts (85.1%) had ≥ 1 AE (14 [20.9%] Grade (Gr) 3-4; 4 [6.0%] Gr 5); 44 (65.7%) had ≥1 treatment-related AE (8 [11.9%] Gr 3-4; 0 Gr 5). Most common total AEs > 15% of total were anaemia, asthenia, cough, fatigue, and nausea. One AE (1.5%) in Cohort 3 led to atezo SC discontinuation. Eleven pts had SC local injection site reactions (mostly Gr 1 [11/12 (90.9%)]). The most common were injection site reaction, pain, and erythema.
Conclusions
In this phase Ib study, atezo SC was well tolerated and provided similar exposure to that of atezo IV. These results support further development of atezo SC in IMscin001 Part 2, a confirmatory phase III study. Table: 1270P
| Atezo | Cohorts (N = 67)a (n) | |||
| 1 (13) | 2 (15) | 3 (39) | ||
| SC mean (SD) treatment duration (d) | SC | 22 (0.0) | 45.1 (15.3) | 56.1 (22.1) |
| Cycle (C) 1 Ctrough (μg/mL) geometric mean GM (%CV) | n SCb | 13 121 (42.8) | 14 83.2 (43.1) | 30 97.3 (43.0) |
| N Ref, IV c,d | 596 74.6 (43.3) c | 426 85.1 (23.1) d | 596 74.6 (43.3) c | |
| C1 AUC(0-Xd) (μg•d/mL) GM (%CV) | n SCb | 13 3870(0-21d) (38.6) | 14 1410(0-14d) (41.8) | 30 2820(0-21d) (38.6) |
| N Ref, IV c,d | 596 2978 (26.1) c | 444 1914 (16.2) d | 596 2978 (26.1) c |
a SC cohorts, site × cycles: 1) thigh × 1; 2) thigh × 3; 3) abdomen × 1, followed by thigh × 2. b Observed C1 Ctrough; AUC. c Model-predicted (MP) C1 Ctrough; AUC(0-21d), OAK (NCT2008227): IV 1200 mg q3w. d MP C1 Ctrough; AUC(0-14d), IMpassion130 (NCT02425891): IV 840 mg q2w.
Clinical trial identification
NCT03735121.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Evelyn Rose, PharmD of Health Interactions, was provided by F Hoffmann–La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche.
Funding
F. Hoffmann-La Roche.
Disclosure
M. Burotto: Honoraria (self), Outside the submitted work: F. Hoffmann-La Roche; Honoraria (self), Outside the submitted work: MSD; Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Bristol-Myers Squibb. E. Felip: Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Janssen; Speaker Bureau/Expert testimony: Medscape; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: prIME Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: F. Hoffmann-La Roche; Advisory/Consultancy: Samsung; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Touchime; Advisory/Consultancy: GSK; Advisory/Consultancy: Bayer; Research grant/Funding (self): Grant for Oncology Innovation (GOI); Research grant/Funding (self): Fundación Merck Salud; Officer/Board of Directors, Independent member of the board: GRÍFOLS. L.A. Herraez Baranda: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. P. Chanu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech/Roche. S. Kshirsagar: Advisory/Consultancy: Genentech, Inc. V. Maiya: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. E. Pozzi, E. Restuccia: Full/Part-time employment: F. Hoffmann-La Roche. All other authors have declared no conflicts of interest.