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748 Phase 1/2 study of the hexavalent OX40 agonist INBRX-106 alone and in combination with pembrolizumab in select solid tumors
  1. Rachel E Sanborn1,
  2. Muhammad Furqan2,
  3. Doug Laux2,
  4. Manish Sharma3,
  5. Daniel Olson4,
  6. David Berz5,
  7. Ralph J Hauke6,
  8. Erminia Massarelli7,
  9. Conor Steuer8,
  10. Elizabeth Davis9,
  11. Wade T Iams9,
  12. Jonathan Thompson10,
  13. John Hamm11,
  14. Vasily Andrianov12,
  15. Brianne O’Neill12,
  16. Yaiza Diaz De Durana12 and
  17. Anthony W Tolcher13
  1. 1Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
  2. 2University of Iowa, Carver College of Medicine, Iowa City, IA, USA
  3. 3START Midwest, Grand Rapids, MI, USA
  4. 4University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
  5. 5Valkyrie Clinical Trials, Los Angeles, CA, USA
  6. 6Nebraska Cancer Specialists, Omaha, NE, USA
  7. 7City of Hope, Duarte, CA, USA
  8. 8Winship Cancer Institute of Emory University, Atlanta, GA, USA
  9. 9Vanderbilt University Medical Center, Nashville, TN, USA
  10. 10Medical College of Wisconsin, Milwaukee, WI, USA
  11. 11Norton Healthcare, Louisville, KY, USA
  12. 12Inhibrx, Inc, La Jolla, CA, USA
  13. 13NEXT Oncology, San Antonio, TX, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background OX40 is a member of the TNF receptor superfamily and a key costimulatory molecule. OX40 signaling can increase T-cell survival, augment clonal expansion of antigen-specific effector and memory T-cell populations, and inhibit regulatory T-cell–induced immunosuppression, making it an attractive therapeutic target. The endogenous trimeric OX40 ligand binds to 3 OX40 molecules to trigger downstream signaling; however, higher-order clustering of OX40 mediates more potent immune stimulation. INBRX-106 is an empirically designed, hexavalent, agonistic, single-domain antibody specific to OX40; the optimized valency of INBRX-106 can enhance OX40 clustering and elicit greater activation of pathways that promote antitumor immunity than bivalent and tetravalent agonists.1 A murine INBRX-106 surrogate showed antitumor activity in mouse tumor models resistant or responsive to checkpoint inhibitors (CPIs). Combination with a PD-1 antagonist increased tumor growth inhibition. We describe a phase 1/2 study evaluating INBRX-106±pembrolizumab in select solid tumors.

Methods This open-label, 4-part, phase 1/2 study (NCT04198766) of INBRX-106±pembrolizumab in patients with locally advanced unresectable or metastatic solid tumors (N≈333) is enrolling in the US (figure 1). Dose escalation (part 1, INBRX-106; part 3, combination) has been completed; the recommended phase 2 dose (RP2D) is being assessed in dose-expansion cohorts (part 2, INBRX-106; part 4, combination). Eligible patients are naive to OX40 agonists with disease that progressed despite all standard therapies or who have no alternative treatment options (except CPI-naive cohorts). Parts 2 and 4 include patients with non-small cell lung cancer (NSCLC), melanoma, head and neck squamous cell carcinoma, gastric or gastroesophageal junction adenocarcinoma, renal cell carcinoma, transitional (urothelial) cell carcinoma, or microsatellite instability (MSI)–/tumor mutation burden (TMB)–high solid tumors. In part 2, any PD-L1 combined positive score (CPS) is permitted in the 3 basket cohorts; patients in a fourth cohort (PD-L1+ NSCLC) require a tumor proportion score (TPS) ≥50% or TMB ≥10 mutations/Mb. Part 4 includes 2 PD-L1+ (CPS ≥1) basket cohorts (1 CPI relapsed/refractory; 1 CPI naive) and 2 CPI-relapsed/refractory PD-L1+ NSCLC cohorts (1 TPS ≥1%; 1 TPS ≥50% or TMB ≥10 mutations/Mb); 3 dosing regimens will be evaluated in the CPI-relapsed/refractory NSCLC cohort requiring TPS ≥50%. Additionally, a basket cohort of mismatch repair–deficient or MSI-high solid tumors and a cohort of uveal melanoma (both CPI relapsed/refractory) will be included.

Primary objectives are safety and determination of the maximum tolerated dose and/or RP2D of INBRX-106±pembrolizumab. Secondary objectives include pharmacokinetics, immunogenicity, and preliminary antitumor activity per RECIST.

Trial Registration identifier, NCT04198766


  1. Rowell E, Kinkead H, Torretti E, et al. INBRX-106: A novel hexavalent anti-OX40 agonist for the treatment of solid tumors. J Immunother Cancer. 2021;9. Abstract 856.

Ethics Approval The study protocol was reviewed and approved by the institutional review board at each participating institution; all patients provided written informed consent.

Abstract 748 Figure 1

Phase 112 study of the hexavalent OX40 agonist INBRX-106 as a single agent and in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors

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