Dose-escalation studies aspire to fill gaps in cancer treatment options

February 2024

This month we’re introducing two early phase trials that are evaluating escalating doses of different potential cancer treatments in patients with advanced solid tumors. These trials are enrolling patients at Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, the only site on the West Coast participating in the studies. Rachel Sanborn, M.D., is the principal investigator in both trials.  

First in-human dosing with HST-1011  

This phase I/II study is evaluating HST-1011, which is being developed for the treatment of patients with advanced solid tumors that have relapsed or are resistant to approved anti-PD(L)1 therapies or other standard of care.  

HST-1011 is an oral CBL-B (Casitas B-lineage lymphoma proto-oncogene B) inhibitor. CBL-B functions as a master regulator of T cell and natural killer cell immunity. Inhibiting its regulatory function may enhance anti-tumor immunity. 

Why this study is important 

Although patients have benefited from many immunotherapies, there remain challenges. For most patients, the benefits are short-lived and appear to be characterized by:  

  • Few or poorly responding immune cells 
  • An inadequate pro-inflammatory response to the tumor  
  • Suppression of inflammation within the tumor microenvironment (Sharma et al, 2017; Lei et al, 2021

New treatment options that help minimize the impact of these forms of resistance are needed to address the challenges. This study is important because published literature and the data from preclinical studies suggest that a CBL-B inhibitor may enhance a person’s immune system.  

Multipart study description 

Phase I of this study has multiple parts: 

  • Patients will receive HST-1011 as either monotherapy (Parts A1 and A2) or in combination with the anti-PD-1 antibody, cemiplimab (Part B).  
  • Part A1 is a first in-human monotherapy dose escalation where cohorts of patients will receive increasing doses of HST-1011.  
  • Part B is a dose escalation of HST-1011 given in combination with the standard dose/regimen of cemiplimab.  

Learn more about the study: 

Open Label, Phase I/II Trial of HST-1011 (SOLAR1) 

Early study of CDX-585 evaluates dose expansion in humans 

CDX-585 is a bispecific antibody that combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. CDX-585 will initially be developed for the treatment of solid tumors either as monotherapy or in combination with other oncologic therapies. Preclinical data presented at the American Association of Cancer Research (AACR) Annual Meeting 2023 demonstrated that CDX-585 is a potent antagonist of both PD-1 and ILT4, and more potent than the combination of separate anti-PD-1 and anti-ILT-4 monoclonal antibodies in several models.  

This study will determine the maximum tolerated dose of CDX-585 while also evaluating its safety, tolerability and efficacy in people with different types of advanced cancers. 

Evaluating tolerated dose in patients 

About 130 patients will be enrolled in this study and closely monitored for a response to the treatment and side effects. 

Participants eligible for the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-585. The dose-escalation part of the study will test the safety of CDX-585 while also determining the dose to be evaluated in the expansion portions of the study. This part of the study will further evaluate the safety of CDX-585 in selected tumor types at the dose level chosen during the escalation part of the study. 

Learn more about this study: 

A study of CDX-585 in patients with advanced malignancies 

Refer a patient   

To refer a patient to one of these clinical trials, contact our clinical research office:     

  • Call 503-215-2614   
  • Submit a referral form    
  • Send an email        

New research studies are added frequently. To see more clinical studies, visit:    

Providence Center of Excellence for precision immuno-oncology and cellular therapy  

Since 1993, cancer research has been the primary focus of the Earle A. Chiles Research Institute, the research arm of Providence Cancer Institute of Oregon. Under the leadership of Walter J. Urba, M.D., Ph.D., our team of physicians and scientists work together to improve cancer treatment methods – seamlessly joining lab research and clinical trials with medical practice.  

Our main area of research is cancer immunotherapy, and with the advancements in genomic sequencing, we are bringing together the power of immunotherapy and personalized medicine to accelerate leading-edge research and groundbreaking discoveries for patients with cancer.  

Learn more about the latest research and clinical trials at the Earle A. Chiles Research Institute.  

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