61MO - IMscin001 (Part 2: Randomized Phase III): Pharmacokinetics (PK), efficacy and safety of atezolizumab (atezo) subcutaneous (SC) vs intravenous (IV) in previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC)

Background

Atezo (anti–PD-L1) IV is approved in NSCLC, SCLC, triple-negative breast cancer, hepatocellular carcinoma, urothelial carcinoma and unresectable/metastatic melanoma. To reduce treatment burden and improve convenience and efficiencies in healthcare, a novel fixed-dose atezo SC co-formulated with recombinant human hyaluronidase is being developed. We report Part 2 (Phase III) of the open-label, randomized, multicentre IMscin001 study (NCT03735121) to investigate non-inferiority of drug exposure at Cycle 1 after atezo SC vs IV administration in NSCLC.

Methods

Adults with previously treated locally advanced/metastatic NSCLC (no prior cancer immunotherapy) and ECOG PS 0 or 1 were randomised 2:1 to receive 2L atezo SC (1875 mg) or IV (1200 mg) every 3 weeks. Primary endpoints: non-inferiority for Cycle 1 observed serum C_trough and model-predicted AUC_{0-21 days}; secondary endpoints: steady-state PK, safety, efficacy (PFS, ORR), patient-reported outcomes, immunogenicity.

Results

There were 247 and 124 patients in the atezo SC and IV arms, respectively (median follow-up: 4.6 mo; data cut-off: 26 Apr 2022). Median age was 64.0 years (range 27–85), 69% were male and 74% had ECOG PS 1. The lower bounds of the 90% CI of the geometric mean ratios (GMRs) for C_trough (GMR 1.05 [90% CI: 0.88, 1.24]) and AUC (GMR 0.87 [90% CI: 0.83, 0.92]) were above the predefined non-inferiority margin of 0.8. Efficacy, immunogenicity and safety were similar between arms (Table). Table: 61MO

^aOS and DoR showed similar trends (immature at primary analysis). ^bProportion of patients with CR/PR per investigator-assessed RECIST 1.1. MP, model-predicted; ss, steady-state.

Conclusions

Atezo SC demonstrated non-inferior exposure vs IV for both co-primary PK endpoints. Efficacy and safety were similar between arms and consistent with the known atezo IV profile; atezo immunogenicity was comparable between arms and within the historical range for atezo IV across indications. These results support atezo SC as an alternative to IV.

Clinical trial identification

NCT03735121.

Editorial acknowledgement

Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Disclosure

M. Burotto: Financial Interests, Personal, Advisory Board, Speaking at industry symposiums and consulting roles: F. Hoffmann-La Roche Ltd, MSD, BMS, AstraZeneca, Novartis; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. Z. Zvirbule: Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. A. Mochalova: Financial Interests, Personal, Stocks/Shares: Medsi Hospital Group; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. Y. Runglodvatana: Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. L.A. Herraez Baranda: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffman-La Roche Ltd. S. Liu: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. P. Chan: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. E. Shearer-Kang: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. M. Shivhare: Financial Interests, Personal, Full or part-time Employment: Roche Products Ltd; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. N. Tosti: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffman-La Roche Ltd. J. Zanghi: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. B. Leutgeb: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. E. Felip: Financial Interests, Personal, Advisory Role, Consultancy/Honoraria: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Ipsen, Janssen, Medical Trends, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Peervoice, Peptomyc, Pfizer, Sanofi, Springer, Takeda, Touchtime; Financial Interests, Institutional, Research Grant: *Fundación Merck Salud, Grant For Oncology Innovation and Merck, Healthcare KGaA; Non-Financial Interests, Personal, Other, Independent Member of the Board: Grifols; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd.