SAKK 35/15: a phase 1 trial of obinutuzumab in combination with venetoclax in patients with previously untreated follicular lymphoma.


Journal

Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425

Informations de publication

Date de publication:
12 07 2022
Historique:
received: 02 11 2021
accepted: 29 04 2022
pubmed: 11 5 2022
medline: 14 7 2022
entrez: 10 5 2022
Statut: ppublish

Résumé

This phase 1 study evaluated safety, tolerability, and preliminary efficacy of obinutuzumab in combination with venetoclax in patients with previously untreated grade 1-3a follicular lymphoma in need of systemic therapy. Two DLs of venetoclax were evaluated with an expansion cohort at the recommended phase 2 dose. Twenty-five patients were enrolled. The recommended phase 2 dose was venetoclax 800 mg OD continuously for 6 cycles starting on day 2 of cycle 1, with obinutuzumab 1000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 to 6, followed by obinutuzumab maintenance every 2 months for 2 years. Only 1 patient had a DLT consisting of grade 4 thrombocytopenia after the first obinutuzumab infusion. Neutropenia was the most common adverse event of grade ≥3 at least possibly attributed to study treatment. Twenty-four patients were evaluable for response after cycle 6 by computed tomography (CT) and 19 by positron emission tomography/CT (PET/CT): overall and complete response rates were 87.5% (95% CI, 67.6% to 97.3%) and 25% (95% CI, 9.8% to 46.7%) in the CT-evaluated patients and 84.2% (95% CI, 60.4% to 96.6%) and 68.4% (95% CI, 43.4% to 87.4%), respectively, in the PET/CT-evaluated patients. One-year progression-free survival was 77.8% (95% CI, 54.6% to 90.1%) and 79% (95% CI, 47.9% to 92.7%) for CT and PET/CT-evaluable patients, respectively, whereas progression-free survival at 30 months was 73.2% (95% CI, 49.8%, 87.0%) as assessed by CT and 79.0% (95% CI, 47.9%, 92.7%) by PET/CT. Despite the activity observed, our results do not support further development of the combination in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02877550.

Identifiants

pubmed: 35537101
pii: 485207
doi: 10.1182/bloodadvances.2021006520
pmc: PMC9278307
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Bridged Bicyclo Compounds, Heterocyclic 0
Sulfonamides 0
venetoclax N54AIC43PW
obinutuzumab O43472U9X8

Banques de données

ClinicalTrials.gov
['NCT02877550']

Types de publication

Clinical Trial, Phase I Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3911-3920

Informations de copyright

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

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Auteurs

Anastasios Stathis (A)

Medical Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.

Ulrich Mey (U)

Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.

Sämi Schär (S)

SAKK Coordinating Center, Bern, Switzerland.

Felicitas Hitz (F)

Oncology/Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Christiane Pott (C)

Medizinischen Klinik II Hämatologie und Internistische Onkologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Nicolas Mach (N)

Service d'Oncologie, Département d'Oncologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland.

Fatime Krasniqi (F)

Medical Oncology, University Hospital of Basel, Basel, Switzerland.

Urban Novak (U)

Department of Medical Oncology, Inselspital/Bern University Hospital, Bern, Switzerland.

Christian Schmidt (C)

Department of Medicine III, University of Munich, Munich, Germany.

Karin Hohloch (K)

Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.

Dirk Lars Kienle (DL)

Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.

Dagmar Hess (D)

Oncology/Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Alden A Moccia (AA)

Medical Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.

Michael Unterhalt (M)

Department of Medicine III, University of Munich, Munich, Germany.

Katrin Eckhardt (K)

SAKK Coordinating Center, Bern, Switzerland.

Stefanie Hayoz (S)

SAKK Coordinating Center, Bern, Switzerland.

Gabriela Forestieri (G)

Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, Switzerland.

Davide Rossi (D)

Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, Switzerland.

Stefan Dirnhofer (S)

Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.

Luca Ceriani (L)

Nuclear Medicine and PET-CT Center, Imaging Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Giulio Sartori (G)

Lymphoma Genomics, Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Francesco Bertoni (F)

Medical Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.
Lymphoma Genomics, Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Christian Buske (C)

Institute of Experimental Cancer Research, CCC Ulm, University Hospital Ulm, Ulm, Germany; and.

Emanuele Zucca (E)

Medical Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.
Department of Medical Oncology, Inselspital/Bern University Hospital, Bern, Switzerland.
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Wolfgang Hiddemann (W)

Department of Medicine III, University of Munich, Munich, Germany.

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