First Patient Dosed in a Phase 1/2 Trial for Small Cell Lung Cancer

First patient dosed in trial of iadademstat plus immunotherapy for small cell lung cancer.

The first patient with small cell lung cancer (SCLC) who has extensive disease has been dosed in a phase 1/2 trial of first-line iadademstat (ORY-1001), a potent and selective LSD1 inhibitor, in combination with immune checkpoint inhibitors, according to a news release from Oryzon Genomics.

The company also added that this is the first clinical trial testing the combination of iadademstat with immune checkpoint inhibitors.

“We are very excited to have the first patient dosed in this study. The biology underlying iadademstat’s ability to make SCLC cells visible to the immune system and to boost significantly the number and the activation of cytotoxic CD8+ T cells is fascinating,” Oryzon’s CEO, Dr. Carlos Buesa, stated in the news release.

“Moreover, prior analyses of several phase 3 trials in SCLC indicate that low LSD1 expression is a key factor in determining patients' likelihood of responding and surviving. If this trial confirms the preliminary findings reported by researchers at MSKCC and others, it would reinforce the rationale for this combination as a therapeutic option for this critically underserved patient population. In the event of positive results, the company could also initiate a complementary trial to generate additional data in support of a potential accelerated registration strategy,” he continued.

More on the Ongoing Trial

This investigation is entitled, “A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer”, according to the news release. Investigators will evaluate the safety, tolerability, dose finding and efficacy of iadademstat in combination with an immune checkpoint inhibitor consisting of either Tecentriq (atezolizumab) or Imfinzi (durvalumab) in patients with extensive-stage small cell lung cancer who have initially received standard of care chemotherapy and immunotherapy.

Notably, according to the American Cancer Society, immune checkpoint inhibitors are a type of cancer treatment that helps the body’s immune system find and attack cancer cells more effectively. These medicines do not kill cancer directly but instead work by blocking certain proteins that cancer uses to hide from the immune system. They are given intravenously or, in some cases, as an injection under the skin.

This early-phase clinical trial is a phase 1/2 study that is led and sponsored by the National Cancer Institute, with Dr. Charles Rudin from Memorial Sloan Kettering Cancer Center serving as the lead investigator. The study will take place at several well-known cancer centers across the United States, including Memorial Sloan Kettering and the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. The trial aims to enroll approximately 45 to 50 patients and is being conducted through a research partnership between Oryzon and the National Cancer Institute.

According to the news release, iadademstat is a small oral drug that blocks a specific enzyme which plays a role in how cancer cells grow and develop. It is being studied for its potential to treat both blood cancers and certain solid tumors. Early clinical trials in patients with relapsed or refractory acute myeloid leukemia have shown that the drug is well-tolerated and has strong clinical activity. Similar results were also seen when iadademstat was used in combination for newly diagnosed, older patients with the disease. 

Moreover, ongoing studies are exploring its use with other treatments, and these studies are supported through partnerships with institutions like the National Cancer Institute and Oregon Health & Science University. Beyond blood cancers, iadademstat is being tested in solid tumors such as small cell lung cancer and neuroendocrine tumors, where it has shown initial signs of activity and safety. Additional trials are underway. 

Iadademstat has also received orphan drug designation for acute myeloid leukemia in both the United States and Europe, and for small cell lung cancer in the United States, the news release concluded.

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