Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers.

BACKGROUND

The programmed death-ligand 1 inhibitor atezolizumab had shown clinical activity against several advanced malignancies.

PATIENTS AND METHODS

This phase II, open-label basket study (NCT02458638) was conducted in 16 main cohorts of patients aged ≥18 years with stage III or IV solid tumors. In stage I, 12 patients were enrolled into each cohort. Treatment was atezolizumab 1200 mg intravenously every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary efficacy endpoint was the non-progression rate (NPR) at 18 weeks in treated, assessable patients. NPR ≤20% was not of interest for development as monotherapy, and NPR ≥40% was defined as the threshold of benefit/success. If ≥3 patients had non-progressive disease in stage I (interim analysis), 13 additional patients could be enrolled into stage II (final analysis). Secondary efficacy and safety endpoints were also evaluated.

RESULTS

Overall, 474 patients were enrolled and treated; 433 were included in the efficacy set. Due partly to slow recruitment because of competing trials and limited efficacy at interim analyses, enrollment was stopped early, including in cohorts that passed stage I boundaries of success. NPR was >20% in five cohorts: cervical cancer {n = 27; NPR 44.4% [95% confidence interval (CI) 25.5% to 64.7%]}; follicular/papillary thyroid cancer [n = 11; 54.5% (95% CI 23.4% to 83.3%)]; thymoma [n = 13; 76.9% (95% CI: 46.2% to 95.0%)]; gastroenteropancreatic (GEP) and lung neuroendocrine tumors [NETs; n = 24; 41.7% (95% CI 22.1% to 63.4%)], and low/intermediate grade carcinoid GEP and lung NETs [n = 12; 58.3% (95% CI 27.7% to 84.8%)]. Treatment-related adverse events occurred in 55.3% of patients overall, and at grade 3, 4, and 5 in 10.3%, 1.7%, and 0.4%, respectively.

CONCLUSIONS

Atezolizumab monotherapy was effective in the cervical cancer cohort. The interim benefit threshold was crossed in patients with follicular/papillary thyroid cancer, thymoma, and GEP and lung NETs, but recruitment was stopped before these signals could be confirmed in stage II. Safety was consistent with previous findings.

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure JT has received consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, Merck Sharp & Dohme (MSD), Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, and TheraMyc; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from F. Hoffmann-La Roche, Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource (PER); and institutional financial support for clinical trials from Amgen Inc., Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA , MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, PharmaMar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc., Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK. FA has received institutional research grants from Novartis, Pfizer, AstraZeneca, Eli Lilly, Daiichi, and F. Hoffmann-La Roche. J-YB has received research grants, consulting fees, lecture fees, and support for attending meetings from F. Hoffmann-La Roche. AB is an employee of F. Hoffmann-La Roche. SF is an employee of F. Hoffmann-La Roche. SG is an employee of F. Hoffmann-La Roche. DJ has received consulting fees from and participated in advisory boards for CureVAC AG, Definiens, F. Hoffmann-La Roche, VAXIMM AG, Oncolytics Biotech Inc., Genmab A-S, Lifescience Inkubator GmbH, and OnkoOne Research and Development GmbH; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from SLK-Kliniken Heilbronn GmbH, Terrapinn, Touch Medical Media, Georg Thieme Verlag, BMS GmbH & Co KGaA, and MSD; payments for expert testimony from Wilhelm-Sander Stiftung, NordForsk, Else-Kröner-Fresenius-Stiftung, and Schering Stiftung; support for attending meetings from Amgen Inc., Oryx GmbH, Roche Glycart AG, Parexel, IKTZ HD GmbH, and BMS; and has a leadership role in BMS Stiftung Immunonkologie. MM has received consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, and support for attending meetings from, and is on advisory boards for, GlaxoSmithKline, BMS, AstraZeneca, F. Hoffmann-La Roche, MSD, Merck, Pierre Fabre, Alfasigma, Eli Lilly, Sanofi, Amgen, SciClone, and Incyte, and holds stock options in Epigen Therapeutics and Theravance. IM received grants from Alligator, AstraZeneca, F. Hoffmann-La Roche, PharmaMar, BMS, and Genmab; consulting fees from F-star, Bioncotech, AstraZeneca, Numab, BMS, PharmaMar, Roche, and Genmab; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, GlaxoSmithKline; and support for attending meetings from F. Hoffmann-La Roche and BMS. LM previously participated in steering committee meetings for the trial but received no remuneration for this. All authors received medical writing assistance with preparation of the manuscript provided by Samantha Santangelo, PhD, of Health Interactions, funded by F. Hoffmann-La Roche. Data sharing Qualified researchers may request access to individual patient-level data through the clinical study data request platform (https://vivli.org/). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).