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Clinical Trial
. 2022 Sep;23(9):1156-1166.
doi: 10.1016/S1470-2045(22)00392-8. Epub 2022 Aug 4.

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial

Neeta Somaiah  1 , Anthony P Conley  2 , Edwin Roger Parra  3 , Heather Lin  4 , Behrang Amini  5 , Luisa Solis Soto  3 , Ruth Salazar  3 , Carmelia Barreto  3 , Honglei Chen  3 , Swati Gite  3 , Cara Haymaker  3 , Elise F Nassif  6 , Chantale Bernatchez  7 , Akash Mitra  8 , John Andrew Livingston  2 , Vinod Ravi  2 , Dejka M Araujo  2 , Robert Benjamin  2 , Shreyaskumar Patel  2 , Maria A Zarzour  2 , Sharjeel Sabir  9 , Alexander J Lazar  10 , Wei-Lien Wang  10 , Najat C Daw  11 , Xiao Zhou  2 , Christina L Roland  6 , Zachary A Cooper  12 , Jaime Rodriguez-Canales  12 , Andrew Futreal  8 , Jean-Charles Soria  13 , Ignacio I Wistuba  3 , Patrick Hwu  14
Affiliations
Clinical Trial

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial

Neeta Somaiah et al. Lancet Oncol. 2022 Sep.

Abstract

Background: Few standard treatment options are available for patients with metastatic sarcomas. We did this trial to evaluate the efficacy, safety, and changes in the tumour microenvironment for durvalumab, an anti-PD-L1 drug, and tremelimumab, an anti-CTLA-4 drug, across multiple sarcoma subtypes.

Methods: In this single-centre phase 2 trial, done at The University of Texas MD Anderson Cancer Center (Houston, TX USA), patients aged 18 years or older with advanced or metastatic sarcoma with an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least one previous line of systemic therapy were enrolled in disease subtype-specific groups (liposarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, alveolar soft-part sarcoma, chordoma, and other sarcomas). Patients received 1500 mg intravenous durvalumab and 75 mg intravenous tremelimumab for four cycles, followed by durvalumab alone every 4 weeks for up to 12 months. The primary endpoint was progression-free survival at 12 weeks in the intention-to-treat population (all patients who received at least one dose of treatment). Safety was also analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02815995, and is completed.

Findings: Between Aug 17, 2016, and April 9, 2018, 62 patients were enrolled, of whom 57 (92%) received treatment and were included in the intention-to-treat population. With a median follow-up of 37·2 months (IQR 1·8-10·1), progression-free survival at 12 weeks was 49% (95% CI 36-61). 21 grade 3-4 treatment-related adverse events were reported, the most common of which were increased lipase (four [7%] of 57 patients), colitis (three [5%] patients), and pneumonitis (three [5%] patients). Nine (16%) patients had a treatment related serious adverse event. One patient had grade 5 pneumonitis and colitis.

Interpretation: The combination of durvalumab and tremelimumab is an active treatment regimen for advanced or metastatic sarcoma and merits evaluation in specific subsets in future trials.

Funding: AstraZeneca.

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Conflict of interest statement

Declaration of interests NS participated in the advisory board of Boehringer Ingelheim. APC reports consulting fees from Deciphera, Inhibrx, Bayer, and Genentech; and participated in the advisory board of Applied Clinical Intelligence. CH reports research funding from Dragonfly and Lovance; salary supported in part by National Institute for Health (NIH) grants (P30CA016672, P50CA221703, U24CA224285, and R01CA236905); consulting fees from Nanobiotix; honoraria from Society for Immunotherapy of Cancer; and stock options from Briacell. SS reports support for attending meetings and travel from Medtronic, and stocks from Inari. AJL reports research funding and consulting fees from, and advisory board membership for AstraZeneca. CLR reports research funding from Bristol Myers Squibb. AF reports research funding paid to institution from NIH (U01 CA224044-02). J-CS reports a leadership role as a fulltime employee at AstraZeneca from September, 2017, to December, 2019; a leadership role as a fulltime employee at Amgen since August, 2021; and is a stock owner from Relay Therapeutics and Gritstone Bio. IIW reports research funding to their institution from Genentech, HTG Molecular, Merck, Bristol Myers Squibb, MedImmune, Adaptive, Adaptimmune, EMD Serono, Pfizer, Takeda, Amgen, Karus, Johnson & Johnson, Bayer, Iovance, 4D, Novartis, and Akoya; scientific and financial support for the institutional Cancer Immune Monitoring and Analysis Center-Cancer Immunologic Data Commons Network through the National Cancer Institute of the NIH Cooperative Agreement U24CA224285); consulting fees from Roche, Bayer, Bristol Myers Squibb, AstraZeneca, Pfizer, HTG Molecular, Merck, GlaxoSmithKline, Guardant Health, Novartis, Flame, Sanofi, Janssen, Daiichi Sankyo, Oncocyte, Amgen, and MSD; and honoraria from Medscape, Roche, Pfizer, AstraZeneca, Platform Health, and Merck. PH reports advisory board membership for Dragonfly Scientific Advisory Board (SAB) and Immatics SAB. All other authors declare no competing interests.

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