Phase I Study of Taminadenant (PBF509/NIR178), an Adenosine 2A Receptor Antagonist, with or without Spartalizumab (PDR001), in Patients with Advanced Non-Small Cell Lung Cancer

  • Clin Cancer Res. 2022 Jun 1;28(11):2313-2320. doi: 10.1158/1078-0432.CCR-21-2742.
Alberto A Chiappori  1 ,  Ben Creelan  1 ,  Tawee Tanvetyanon  1 ,  Jhanelle E Gray  1 ,  Eric B Haura  1 ,  Ram Thapa  2 ,  Margaret L Barlow  3 ,  Zhihua Chen  2 ,  Dung Tsa Chen  2 ,  Amer A Beg  1  3 ,  Theresa A Boyle  4 ,  Julio Castro  5 ,  Liza Morgan  6 ,  Erick Morris  7 ,  Mehreteab Aregay  6 ,  Felipe K Hurtado  6 ,  Luigi Manenti  7 ,  Scott Antonia  8
Affiliations
  • 1. Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
  • 2. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
  • 3. Department of Immunology, Moffitt Cancer Center, Tampa, Florida.
  • 4. Department of Pathology, Moffitt Cancer Center, Tampa, Florida.
  • 5. Palobiofarma S.L., Navarra, Spain.
  • 6. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
  • 7. Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • 8. Duke Cancer Institute, Durham, North Carolina.
PMID: 35254415 DOI: 10.1158/1078-0432.CCR-21-2742
Abstract

Purpose: The adenosine 2A receptor (A2AR) mediates the immunosuppressive effects of adenosine in the tumor microenvironment and is highly expressed in non-small cell lung Cancer (NSCLC). Taminadenant (PBF509/NIR178) is an A2AR antagonist able to reactivate the antitumor immune response.

Patients and methods: In this phase I/Ib, dose-escalation/expansion study, patients with advanced/metastatic NSCLC and ≥1 prior therapy received taminadenant (80-640 mg, orally, twice a day) with or without spartalizumab (anti-programmed cell death-1, 400 mg, i.v., every 4 weeks). Primary endpoints were safety, tolerability, and feasibility of the combination.

Results: During dose escalation, 25 patients each received taminadenant alone or with spartalizumab; 19 (76.0%) and 9 (36.0%) had received prior immunotherapy, respectively. Dose-limiting toxicities (all Grade 3) with taminadenant alone were alanine/aspartate aminotransferase increase and nausea [n = 1 (4.0%) each; 640 mg], and in the combination group were pneumonitis [n = 2 (8.0%); 160 and 240 mg] and fatigue and alanine/aspartate aminotransferase increase [n = 1 (4.0%) each; 320 mg]; pneumonitis cases responded to Steroids rapidly and successfully. Complete and partial responses were observed in one patient each in the single-agent and combination groups; both were immunotherapy naïve. In the single-agent and combination groups, 7 and 14 patients experienced stable disease; 7 and 6 patients were immunotherapy pretreated, respectively.

Conclusions: Taminadenant, with and without spartalizumab, was well tolerated in patients with advanced NSCLC. The maximum tolerated dose of taminadenant alone was 480 mg twice a day, and 240 mg twice a day plus spartalizumab. Efficacy was neither a primary or secondary endpoint; however, some clinical benefit was noted regardless of prior immunotherapy or programmed cell death ligand-1 status.

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