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Clinical Trial
. 2022 Apr 20;40(12):1291-1300.
doi: 10.1200/JCO.20.03452. Epub 2021 Jul 14.

Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1

Sant P Chawla  1 , Brian A Van Tine  2 , Seth M Pollack  3   4 , Kristen N Ganjoo  5 , Anthony D Elias  6 , Richard F Riedel  7 , Steven Attia  8 , Edwin Choy  9 , Scott H Okuno  10 , Mark Agulnik  11   12 , Margaret von Mehren  13 , Michael B Livingston  14 , Vicki L Keedy  15 , Claire F Verschraegen  16 , Tony Philip  17 , G Chet Bohac  18   19 , Sergey Yurasov  18   20 , Adam Yakovich  18   21 , Hailing Lu  18   22 , Michael Chen  18   23 , Robert G Maki  24
Affiliations
Clinical Trial

Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1

Sant P Chawla et al. J Clin Oncol. .

Abstract

Purpose: CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti-programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma.

Patients and methods: Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed.

Results: A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1-specific T cells (P = .01) and NY-ESO-1-specific antibody responses (P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02).

Conclusion: Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti-programmed death ligand-1 therapies merits further evaluation in other clinical contexts.

Trial registration: ClinicalTrials.gov NCT02609984.

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Conflict of interest statement

Sant P. ChawlaStock and Other Ownership Interests: AADi, Cellestia Biotech, Immix BioPharmaHonoraria: Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research through Collaboration, Janssen, Advenchen Laboratories, Bayer, InhibRx, NKMax, TymeConsulting or Advisory Role: Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research through Collaboration, Janssen, Advenchen Laboratories, Bayer, NKMax, InhibRxSpeakers' Bureau: Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research through Collaboration, JanssenResearch Funding: Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research through Collaboration, Janssen, Advenchen Laboratories, Bayer, InhibRx, NKMax Brian A. Van TineLeadership: PolarisConsulting or Advisory Role: EMD Serono, Novartis, Epizyme, Daiihi Sankyo, Pfizer, Adaptimmune, Bayer, GlaxoSmithKline, Lilly, Cytokinetics, Apexigen, Deciphera Pharmaceuticals, Immune Design, ADRxSpeakers' Bureau: Novartis, Lilly, Adaptimmune, GlaxoSmithKlineResearch Funding: Pfizer, Merck, TRACON Pharma, GlaxoSmithKlinePatents, Royalties, Other Intellectual Property: Patent on the use of ME1 as a biomarker, Patent on ALEXT3102, Accuronix Therapeutics—Licensing agreement. Sigma-2 Receptor Ligands and Therapeutic Uses Therefor (006766), Modular Platform for Targeted Therapeutic Delivery (006755), Sigma-2 Receptor Ligand Drug Conjugates as Antitumor Compounds, Methods of synthesis and Uses Thereof (014229)Expert Testimony: Health AdvancesTravel, Accommodations, Expenses: Adaptimmune, Advenchen Laboratories, GlaxoSmithKline, Lilly Seth M. PollackConsulting or Advisory Role: GlaxoSmithKline, Daichii Sankyo, Apexigen, T-KnifeResearch Funding: Merck, EMD Serono, Incyte Kristen N. GanjooConsulting or Advisory Role: Daiichi Sankyo, Foundation Medicine, Deciphera Anthony D. EliasStock and Other Ownership Interests: AbbVie, Merck, Gilead Sciences, Allergan, Pfizer, Abbott Laboratories, Amgen, Bristol Myers Squibb, United Health Group, Align Oncology, Illumina, Exact Sciences, Lilly, Agilent, Cigna, Alexion Pharmaceuticals, BiogenerixConsulting or Advisory Role: Ayala PharmaceuticalsResearch Funding: Medivation, Astellas Pharma, Genentech, Deciphera, Xencor, Infinity Pharmaceuticals, Karyopharm Therapeutics, TopAlliance BioSciences Inc, Fosun Orinove, BioAtlaUncompensated Relationships: Seiyax Richard F. RiedelEmployment: LimbguardLeadership: LimbguardStock and Other Ownership Interests: LimbguardConsulting or Advisory Role: Daiichi Sankyo, Loxo, Ignyta, Bayer, NanoCarrier, Deciphera, SpringWorks Therapeutics, Blueprint MedicinesResearch Funding: TRACON Pharma, Bayer, Karyopharm Therapeutics, Immune Design, AADi, Plexxikon, Arog, Lilly, Daiichi Sankyo, Ignyta, Roche/Genentech, NanoCarrier, GlaxoSmithKline, SpringWorks Therapeutics, Blueprint Medicines, Epizyme, PhilogenPatents, Royalties, Other Intellectual Property: PandoNet—LimbguardTravel, Accommodations, Expenses: Daiichi Sankyo, Ignyta, NanoCarrier Steven AttiaResearch Funding: AB Science, TRACON Pharma, Bayer, Novartis, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Desmoid Tumor Research Foundation, Merck, Philogen, Gradalis, Deciphera, Takeda, Incyte, SpringWorks Therapeutics, Adaptimmune, Advenchen Laboratories, Bavarian Nordic, BTG, PTC Therapeutics, GlaxoSmithKline, FORMA Therapeutics Edwin ChoyResearch Funding: Novartis, Amgen, AstraZeneca, Mirati Therapeutics, Exelixis, Iterion Therapeutics, Immune Design, Lilly, AdaptimmuneOpen Payments Link: https://openpaymentsdata.cms.gov/physician/584027 Mark AgulnikConsulting or Advisory Role: Lilly, Adaptimmune, Regeneron, AstraZenecaSpeakers' Bureau: Bristol Myers Squibb, Bayer, DecipheraResearch Funding: Exelixis Margaret von MehrenConsulting or Advisory Role: Deciphera, ExelixisResearch Funding: ArQule, Novartis, Blueprint Medicines, Deciphera, Gradalis, Springworks Therapeutics, Lilly, Arog, Genmab, ASCOTravel, Accommodations, Expenses: Deciphera Pharmaceuticals, NCCNOther Relationship: NCCN Vicki L. KeedyConsulting or Advisory Role: Karyopharm Therapeutics, Daiichi Sankyo/LillyResearch Funding: MedPacto, Plexxikon, Daiichi Sankyo, Lilly, Immune Design, GlaxoSmithKline, TRACON Pharma, Advenchen Laboratories, Adaptimmune, Deciphera, SpringWorks Therapeutics Tony PhilipConsulting or Advisory Role: Foundation Medicine, Daiichi Sankyo/Astra Zeneca, Deciphera G. Chet BohacEmployment: MacrogenicsStock and Other Ownership Interests: Amgen, Macrogenics Sergey YurasovEmployment: Immune Design, Nuvation BioLeadership: Immune DesignStock and Other Ownership Interests: Nuvation Bio Adam YakovichStock and Other Ownership Interests: Replimune, Karyopharm TherapeuticsConsulting or Advisory Role: Merck Hailing LuEmployment: SeagenStock and Other Ownership Interests: Seagen Michael ChenEmployment: Sanamo Therapeutics, Immune DesignStock and Other Ownership Interests: Sangmo Robert G. MakiConsulting or Advisory Role: Bayer, Karyopharm Therapeutics, Deciphera, TRACON PharmaResearch Funding: Regeneron, Daiichi, Bayer, SpringWorks TherapeuticsPatents, Royalties, Other Intellectual Property: UpToDate: I write and edit chapters for their online textbookTravel, Accommodations, Expenses: TRACON Pharma, SpringWorks TherapeuticsOpen Payments Link: https://openpaymentsdata.cms.gov/physician/205679/summaryNo other potential conflicts of interest were reported.

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