Immunotherapies for GI and lung cancers evaluated in new studies

November 2023 issue

This month we’re featuring three clinical trials open at multiple Providence Cancer Institute of Oregon sites. The first study is for people with locally advanced or metastatic gastric, gastroesophageal junction (GEJ) and esophageal adenocarcinoma. The two studies that follow are for people with non-small cell lung cancer (NSCLC) – locally advanced, unresectable or metastatic NSCLC and stage I NSCLC, respectively. All three studies are currently enrolling trial participants.  

Phase III clinical trial for people with gastric and esophageal cancers 

Globally, gastric and esophageal cancers are the fifth and seventh most frequently diagnosed cancers, respectively. Although the incidence of these cancers is lower in the United States than in other parts of the world, survival rates for people with locally advanced cancer that cancer that has spread outside the area where it started to other parts of the body (metastatic) or cannot be removed by surgery (unresectable) is approximately 5%, regardless of where they live.   

ARCUS STAR-221 is designed to offer a more hopeful treatment option with higher survival rates for people with these cancers. The trial is currently enrolling people with locally advanced or metastatic gastric, GEJ and esophageal adenocarcinoma that can’t be surgically removed. The principal investigator is Gina Vaccaro, M.D., medical director of Gastrointestinal Cancer Research at Providence Cancer Institute.  

Previous studies show improved treatment options   

In recent studies, adding programmed cell death protein 1 (PD-1) inhibitors to standard chemotherapy have resulted in a higher survival rate for people with locally advanced unresectable and/or metastatic cancer over chemotherapy alone. Additionally, other studies suggest that anti-T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) agents work in combination with anti-PD-1/PD-L1 inhibitors in a variety of advanced solid malignancies, with and without chemotherapy. As a result, several clinical trials, including ARCUS STAR-221, are currently combining anti-TIGIT and anti-PD-1/PD-L1 therapies to treat a variety of cancers, including esophageal, GEJ and gastric cancers.  

ARCUS STAR-221 compares the efficacy of these first-line treatments:  

  • The anti-TIGIT monoclonal antibody domvanalimab, the anti-PD-1 monoclonal antibody zimberelimab, and chemotherapy (FOLFOX: oxaliplatin, leucovorin, fluorouracil) or (CAPOX: capecitabine and oxaliplatin), based on investigator decision   
  • The anti-PD-1 monoclonal antibody nivolumab and chemotherapy (FOLFOX or CAPOX) 

Domvanalimab works by binding to TIGIT, which may activate the immune system to attack and destroy cancer cells.  As anti-PD-1 monoclonal antibodies, zimberelimab and nivolumab block the protein PD-1, which can act as a brake on the immune system. Nivolumab is used alone or in combination to treat multiple tumor types. Zimberelimab is considered an investigational medication, although in 2023 it was approved for use in China as a treatment for cervical cancer.  

This trial is open to approximately 970 people who will be randomly assigned to either: 

 Arm A (Experimental Arm) 

  • Domvanalimab + zimberelimab once every four weeks in addition to chemotherapy with FOLFOX once every two weeks or 
  • Domvanalimab + zimberelimab once every three weeks in addition to chemotherapy with CAPOX once every three weeks 

Arm B (Comparator Arm) 

• Nivolumab once every two weeks + FOLFOX once every two weeks or 

• Nivolumab once every three weeks + CAPOX once every three weeks 

ARCUS STAR-221 is offered by Earle A. Chiles Research Institute, a division of Providence Cancer Institute.  The trial is currently enrolling patients at two locations in the Portland area.  

Learn more about this study: 

ARCUS STAR-221: Randomized phase III trial of domvanalimab + zimberelimab + chemotherapy vs. nivolumab + chemotherapy in adults with advanced upper gastrointestinal tract adenocarcinoma

Study will evaluate investigational medications for people with NSCLC  

With over two million new diagnoses each year, and nearly two million deaths worldwide, lung cancer is one of the most common malignancies in adults, according to the World Health Organization. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80-85% of all cases.  

The prognosis for people with lung cancer generally depends on the stage at which cancer is detected. When found early, a cure is possible through surgery, radiation and/or chemotherapy and immunotherapy. However, over half of all people with newly diagnosed NSCLC have stage IV cancer (cancer that has spread outside the lung where it started to other areas in the body). This condition may be able to be treated, but generally not cured. Treatment depends on several factors, including the presence of actionable mutations – DNA alterations that can affect a cancer’s response to treatment – in which case, a targeted therapy may be the best option. For people with NSCLC without mutations, however, there is an urgent need to find therapies that can improve responses and clinical benefit. 

BGB-LC-201 is a phase II clinical trial designed to address this need. The randomized study will evaluate the antitumor activity, safety and tolerability of multiple new investigational medications in patients with stage IV NSCLC without actionable mutations. Trial participants will receive tislelizumab, a humanized monoclonal antibody that targets programmed cell death protein-1 (PD-1), plus one of two investigational agents (BGB-A445 or LBL-007) with or without chemotherapy.  

Cancer cells can use the PD-1 pathway to hide from T cells, which detect and fight infections and diseases like cancer. By hiding in PD-1 pathways, cancer cells can evade T cells and then grow and spread. 

Although targeting PD-1 has shown some benefit, not all patients who receive the therapy have prolonged survival. Also, the addition of chemotherapy to medications such as tislelizumab has improved overall survival in patients with NSCLC, but it is associated with chemotherapy-induced side effects.  

Adding the investigational immunotherapy agents, such as the two used in this trial, may be able to cooperate with and improve the efficacy of immune checkpoint inhibitors and may be beneficial to patients with NSCLC.   

This randomized study is designed with two separate sub-studies: 

  • Sub-study 1 includes participants with NSCLC with a PD-L1 expression greater than or equal to 50%.  
  • Arm 1A: Tislelizumab + BGB-A445 
  • Arm 2A: Tislelizumab + LBL-007 
  • Reference arm: Tislelizumab alone 
  • Sub-study 2 includes participants with NSCLC with PD-L1 expression of less than 50%. 
  • Arm 1A: Tislelizumab + chemotherapy + BGB-A445 
  • Arm 1B: Tislelizumab + chemotherapy + LBL-007 
  • Reference arm: Tislelizumab + chemotherapy 

Rachel E. Sanborn, M.D., medical director of the Providence Thoracic Oncology Program and of the Phase I Clinical Trials Program at Providence Cancer Institute, is the principal investigator. Providence Cancer Institute offers two sites in Oregon for patients enrolling in this trial.  

Learn more about this trial:  

BGB-LC-201: Phase II, open-label, multi-arm study of tislelizumab in combination with investigational agents with or without chemotherapy 

Addressing gap in treatment options for people with stage I NSCLC 

A new clinical trial offered by Earle A. Chiles Research Institute is enrolling patients with stage I NSCLC to evaluate the efficacy of pembrolizumab following surgical resection of the tumor, versus observation following surgical resection. Pembrolizumab is an immunotherapy that works by blocking the PD-1 pathway, which in turn helps prevent cancer cells from hiding. 

Standard of care treatment for patients with stage I NSCLC and tumors less than 4 cm (about 1.57 in) is surgery. However, the rate of relapse is between 20-30%, mostly due to the cancer metastasizing. Chemotherapy after surgery has not been effective in reducing the risk of relapse in these patients.  

But PD-1 inhibitors have proven effective in the treatment of patients with advanced NSCLC, and small studies suggest they may be effective in treating early-stage cancer. 

Although immunotherapies like PD-1/PD-L1 inhibitors are being assessed in ongoing trials of patients with early-stage NSCLC, most of these studies exclude patients with tumors less than 4 cm, despite high rates of relapse. This randomized, two-arm study is designed to address the unique gap in treatment options for these patients.  

Rachel E. Sanborn, M.D., medical director of the Providence Thoracic Oncology Program and of the Phase I Clinical Trials Program at Providence Cancer Institute, is the principal investigator. Providence Cancer Institute offers two sites in Oregon for patients enrolling in this trial. 

Learn more about this trial: 

BTCRC-LUN18-153: Randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I NSCLC with primary tumors between 1-4 cm 

For more information about any of these studies or to refer a patient, please contact our staff in Clinical Research:  

See current and past studies at Providence Cancer Institute:   

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