The Duke Cancer Institute (DCI) Thoracic Oncology Program is currently leading seven active Wake County clinical trials exploring various leading-edge immune-modulating therapies to treat non-small cell lung cancer (NSCLC). Many of these trials are led by medical oncologist and researcher Joel R. Rivera Concepcion, MD, JD.

“S2302 Pragmatica is one of our most exciting and potentially promising trials,” says Rivera. 

S2302 Pragmatica is a phase 3 trial testing a chemo-free combination of pembrolizumab (a PD-1 inhibitor) and ramucirumab (a VEGFR2 inhibitor) against the standard of care chemotherapy for recurrent NSCLC. The combination of pembrolizumab and ramucirumab has shown encouraging results in previous phase trials, and patients could benefit from treatments with fewer systemic side effects compared to chemotherapy.

The Pragmatica clinical trial design is novel and inclusive. “It’s a patient-centered design with a wider qualification criterion. More patients in our community can benefit from it,” says Rivera. “This could be a good option for patients who have relapsed cancer and are seeking novel treatment options close to home.”

Two studies in the team’s portfolio are site-specific phase 2 trials: TOP 2101 and TOP 2201.

“The TOP 2101 and TOP2201 trials are only available at Duke, and they are testing a very promising treatment using a class of drugs called PCSK9 inhibitors,” says Rivera. “It could be a game-changer in cancer treatment because previous studies show they may generate an anticancer effect and clinical responses in NSCLC.” 

Scott J. Antonia, MD, PhD, director of DCI Center for Cancer Immunotherapy and medical oncologist with the thoracic oncology group, is leading the TOP 2101 and TOP 2202 studies. PCSK9 inhibitors are currently FDA-approved for lowering low-density lipoprotein (LDL) in cholesterol management, but evidence suggests they may have additional applications in cancer treatment. Studies have shown that PCSK9 inhibitors ignite the immune system and initiate a greater immunotherapy response.

“TOP 2201 is a phase 2 trial, so all enrolled patients get the experimental agents. It’s a trial for patients who have refractory or relapsed NSCLC. We’re studying if giving the PCSK9 inhibitor alirocumab in combination with the PD-1inhibitor cemiplimab is effective,” says Rivera. 

TOP 2101 also studies a PCSK9 inhibitor (evolocumab) given with PD-1 inhibitors (ipilimumab and nivolumab), but as a first-line treatment for stage IV, PD-L1 negative NSCLC.  

A strength of the DCI thoracic cancer clinical trial portfolio is the connection to additional clinical trial options. “Some patients enrolled in a TOP study can flow into Pragmatica or another study,” says Rivera. Patients with refractory or advanced cancer have more treatment options. 

The team is expanding open trials in Wake County and contributes to trials at the Duke campus in Durham. “Many of us split our time between Wake County and Durham, so we’re very involved in trials happening at both sites. We can offer more to patients and maintain continuity of care if we find a trial better suited for a patient at either location,” says Rivera. 

Many of the team’s trials support the overall movement in cancer treatment to reduce chemotherapy with targeted therapy aimed at dismantling the cancer genetic aberrancies, as well as immunotherapy. Trial A082002 tests if stereotactic body radiation therapy (SBRT) with the standard of care treatment enhances the immune system response, making the standard treatment more effective. 

“This is the future of oncology, and we’re a premier academic institution committed to leading the field of immunotherapy and targeted therapy in thoracic malignancies,” says Rivera.