Abstract 845P
Background
Corticosteroid replacement therapy (CRT) in patients (pts) with adrenal insufficiency (AI) could reduce the efficacy of immunotherapy. Vidutolimod (vidu) is an immunostimulatory virus-like particle containing a CpG-A Toll like receptor 9 (TLR9) agonist. In a phase 1b study in pts with anti–PD-1–refractory melanoma, vidu + pembrolizumab (pembro) showed promising clinical activity with an objective response rate (ORR) of 23.5% (95% CI, 15.5-33.1). This post hoc analysis assessed the safety and clinical activity in the subgroup of pts with AI on CRT.
Methods
This study (NCT02680184) enrolled adults with etastatic or unresectable cutaneous melanoma with progressive disease or stable disease after ≥12 weeks of anti−PD-1 treatment (tx), measurable disease per RECIST v1.1, ECOG PS 0/1, and ≥1 lesion accessible for intratumoral (IT) injection. This post hoc analysis included all pts who received IT vidu + IV pembro. Pts with AI were to receive CRT (prednisone-equivalent 5-10 mg daily) and prophylactic stress-dose steroids (50-100 mg hydrocortisone or equivalent orally every 8 hours) before and for 24-48 hours after vidu dosing. The primary objective was safety, and the key secondary objective was ORR.
Results
159 pts received vidu + pembro. All pts had prior anti–PD-1 tx, and 74 pts (46.5%) had prior ipilimumab (ipi) tx. 148 pts (93.1%) had progressive disease on last anti–PD-1 tx. 20 pts (12.6%) had a medical history of AI; 19 of these pts (95.0%) had prior ipi tx. 5 additional pts (3.1%; 4 with prior ipi tx) were diagnosed with AI on study. Grade 3/4 tx-emergent adverse events were reported in 11 pts (55.0%) with prior AI and in 3 pts (60.0%) diagnosed with AI on study. No tx-related deaths occurred. The ORR was 28.0% (7/25; 95% CI, 12.1-49.4) in pts with AI.
Conclusions
The safety and ORR of vidu + pembro in pts with AI were consistent with the overall study population, suggesting that simultaneous corticosteroids for AI do not reduce the biologic activity of this combination. A phase 2 study to confirm the efficacy of vidu + anti–PD-1 in pts with PD-1 blockade–refractory melanoma is ongoing (NCT04698187).
Clinical trial identification
NCT02680184.
Editorial acknowledgement
This work was supported by Checkmate Pharmaceuticals. Medical writing assistance was provided by Steffen Biechele, PhD (ApotheCom, San Francisco, CA, USA), and funded by Checkmate Pharmaceuticals.
Legal entity responsible for the study
Checkmate Pharmaceuticals, Inc.
Funding
Checkmate Pharmaceuticals, Inc.
Disclosure
J.M. Kirkwood: Financial Interests, Institutional, Research Grant: Amgen, Bristol Myers Squibb, Castle Biosciences, Inc., Checkmate Pharmaceuticals, Inc., Harbour BioMed, Immvira Pharma Co., Immunocore LLC, Iovance Biotherapeutics, Novartis Pharmaceuticals, Schering-Plough, Takeda, Verastem, Inc.; Financial Interests, Institutional, Funding: Amgen, Bristol Myers Squibb, Castle Biosciences, Inc., Checkmate Pharmaceuticals, Inc., Harbour BioMed, Immvira Pharma Co., Immunocore LLC, Iovance Biotherapeutics, Novartis Pharmaceuticals, Schering-Plough, Takeda, Verastem, Inc.; Financial Interests, Personal, Advisory Role: Applied Clinical Intelligence, LLC, Amgen, Inc., Ankyra Therapeutics, Axio Research/Instil Bio, Becker Pharmaceutical Consulting, Bristol Myers Squibb, Checkmate Pharmaceuticals, Inc., DermTech, Fenix Group International, Harbour BioMed, Immunocore LLC, Intellisphere LLC/Cancer Network, Iovance Biotherapeutics, IQVIA, Istari Oncology, Merck, Millenium Pharmaceuticals/Takeda Pharmaceuticals, Novartis, OncoCyte Corporation, OncoSec Medical Inc., Pfizer, Replimune, Scopus BioPharma, SR One Capital Management. Y. Zakharia: Financial Interests, Personal, Advisory Role: Amgen, Array BioPharma, Castle Bioscience, Clovis Oncology, Eisai, EMD Serono, Exelixis, Janssen, Novartis, Pfizer, Roche Diagnostics; Financial Interests, Institutional, Research Grant: Eisai, Exelixis, Lumos Pharma, Pfizer; Financial Interests, Institutional, Funding: Eisai, Exelixis, Lumos Pharma, Pfizer; Financial Interests, Personal, Other, Member of data safety and monitoring committee: Janssen, TTC Oncology. D. Davar: Financial Interests, Personal, Advisory Role: Array BioPharma, Bristol Myers Squibb, Instil Bio, Immunocore, Merck, Tesaro, Verdanta Biosciences; Financial Interests, Institutional, Research Grant: Arcus, BMS, Checkmate, Cellsight, GSK/Tesaro, Immunocore, Merck; Financial Interests, Institutional, Funding: Arcus, BMS, Checkmate, Cellsight, GSK/Tesaro, Immunocore, Merck. E. Buchbinder: Financial Interests, Institutional, Research Grant: Lilly, Novartis, Partners Therapeutics, Genentech, BVD; Financial Interests, Institutional, Funding: Lilly, Novartis, Partners Therapeutics, Genentech, BVD; Financial Interests, Personal, Advisory Role: Nektar, Novartis, Apexigen, Shionogi, BMS. T. Medina: Financial Interests, Personal, Advisory Role: Array BioPharma, Bristol Myers Squibb, Checkmate Pharmaceuticals, Iovance Biotherapeutics; Financial Interests, Institutional, Research Grant: Pfizer, Bristol Myers Squibb, Checkmate Pharmaceuticals, Iovance Biotherapeutics, Merck, Day One Biopharmaceuticals, NeraCare GmbH, Replimune, BioAtla, Exicure, Taiga Biotechnologies; Financial Interests, Institutional, Funding: Pfizer, Bristol Myers Squibb, Checkmate Pharmaceuticals, Iovance Biotherapeutics, Merck, Day One Biopharmaceuticals, NeraCare GmbH, Replimune, BioAtla, Exicure, Taiga Biotechnologies. A. Daud: Financial Interests, Personal, Other, Honoraria: Array BioPharma, F. Hoffman-LaRoche AG; Financial Interests, Personal, Advisory Role: Novartis, Merck Sharp & Dohme, ER Squibb & Sons LLC; Financial Interests, Institutional, Research Grant: Merck, Novartis, Incyte Corp, Array Biopharma, ER Squibb & Sons LLC; Financial Interests, Institutional, Funding: Merck, Novartis, Incyte Corp, Array Biopharma, ER Squibb & Sons LLC; Financial Interests, Personal, Other, Travel expenses: Novartis, ER Squibb & Sons LLC, Merck Sharp & Dohme, Array BioPharma, F. Hoffman-La Roche AG, EMD Serono; Non-Financial Interests, Personal, Other: EMD Serono. A. Ribas: Financial Interests, Personal, Advisory Role: Amgen, Bristol Myers Squibb, Chugai Pharmaceutical, Genentech, Merck, Novartis, Roche, Sanofi; Financial Interests, Personal, Stocks/Shares: Advaxis, Arcus Biosciences, Biontech Therapeutics, Compugen, CytomX, Five Prime Therapeutics, RAPT Therapeutics (formerly FLX Bio), ImaginAb, IsoPlexis, Kite-Gilead, Lutris Pharma, Merus, PACT Pharma, Rgenix, Tango Therapeutics; Financial Interests, Personal, Officer: Advaxis, Arcus Biosciences, Bioncotech Therapeutics, Compugen, CytomX, Five Prime Therapeutics, RAPT Therapeutics (formerly FLX Bio), ImaginAb, IsoPlexis, Kite-Gilead, Lutris Pharma, Merus, PACT Pharma, Rgenix, Tango Therapeutics. B. Chmielowski: Financial Interests, Personal, Advisory Role: Iovance, IDEAYA, Sanofi, OncoSec, Genentech, Nektar, Novartis, Delcath, InstilBio; Financial Interests, Institutional, Research Grant: BMS, Macrogenics, Array Biopharma, Daiichi Sankyo, Merck, Karyopharm, Infinity, Rgenix, Biothera, Advenchen, Idera, Neon Therapeutics, Xencor, Compugen, PACT, Immunocore, Lilly, IDEAYA, Tolero, Ascentage, Novartis, Atrecam Replimune, Instil Bio, Adagene; Financial Interests, Personal, Other, Travel expenses: Instil Bio. J.J. Niu: Financial Interests, Personal, Advisory Role: AstraZeneca, BeiGene, Blueprint Medicines, Bristol Myers Squibb, Exact Sciences, Immvira, Johnson & Johnson, Merck, Mirati Therapeutics, Takeda; Financial Interests, Personal, Speaker’s Bureau: Naveris, Onclive. G.T. Gibney: Financial Interests, Personal, Advisory Role: Merck, Novartis, Bristol Myers Squibb, Eisai, Exicure, Genentech, Regeneron, Sapience Therapeutics; Financial Interests, Institutional, Research Grant: Exelixis, Lucerno Dynamics. K.A. Margolin: Financial Interests, Personal, Advisory Role: Werewolf, Xilio, Instil, Checkmate Pharmaceuticals, ImaginAb; Financial Interests, Institutional, Research Grant: BMS, Regeneron, IO Biotech, Agenus, Merck, Ultimovacs, BioNTech, Roche, Moderna. A.J. Olszanski: Financial Interests, Personal, Advisory Role: BMS, Merck, Eisai, Takeda, Novartis, Nektar, InstilBio; Financial Interests, Institutional, Research Grant: Alkermes, Astellas, BMS, Checkmate Pharmaceuticals, Gan & Lee, GlycoNex, Intensity Therapeutics, InstilBio, Kadmon, Kartos, Neoimmune, OncoSec, SoundBiologics, SpringBank, Sumitomo Dainipopon Pharma, Takeda, Targovax, GSK, Regeneron. T. Sato: Financial Interests, Personal, Advisory Role: Immunocorep, Castle Biosciences. L. Zhao: Financial Interests, Personal, Full or part-time Employment: Checkmate Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Checkmate Pharmaceuticals; Financial Interests, Invited Speaker: Codiak Biosciences. D. Bobilev: Financial Interests, Personal, Full or part-time Employment: Checkmate Pharmaceuticals. A.M. Krieg: Financial Interests, Personal, Stocks/Shares: Checkmate Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment: Checkmate Pharmaceuticals; Financial Interests, Personal, Licensing Fees: Checkmate Pharmaceuticals; Financial Interests, Personal, Royalties: Checkmate Pharmaceuticals. J. Wooldridge: Financial Interests, Personal, Full or part-time Employment: Checkmate Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Checkmate Pharmaceuticals. M. Milhem: Financial Interests, Personal, Officer: Exicure; Financial Interests, Personal, Advisory Role: Amgen, Array BioPharma, BioNTech, Blueprints Medicine, Immunocore, Novartis, Trieza Therapeutics. All other authors have declared no conflicts of interest.