FDA Grants 2 Orphan Drug Designations to THIO for HCC and SCLC

The FDA has granted 2 orphan drug designations to the anti-cancer agent, THIO, based on preclinical efficacy of the agent for hepatocellular carcinoma (HCC) and small cell lung cancer (SCLC), according to MAIA Biotechnology.¹

In the upcoming THIO-102 trial, investigators will examine the safety and efficacy of THIO administered in sequence with the immunotherapies pembrolizumab (Keytruda) or atezolizumab (Tecentriq) across multiple tumor types, including SCLC, liver cancer, and colorectal cancer.

A third immunotherapy checkpoint inhibitor, including nivolumab (Opdivo), durvalumab (Imfinzi), or dostarlimab (Jemperli), could be added to the sequence in the future.

“The THIO-102 trial is operationally on track to begin enrolling patients later this year,” said Mihail Obrocea, MD, chief medical officer of MAIA, in the press release. “Based on the data generated on these indications, we are targeting accelerated approvals in these tumor types; in addition, we have now added a fourth arm which includes solid tumors of all types, that will serve as a signal generation arm; we will include telomerase positive breast, prostate, gastric, pancreatic, ovarian, along with potentially other tumor types.”

THIO is a telomere-targeting agent that is in clinical development for patients with non–small cell lung cancer (NSCLC). Telomeres play a fundamental role in the survival of cancer cells as well as their resistance to current therapies. Treatment with THIO is being developed in the second-line of treatment and higher for patients with NSCLC that have progressed beyond the standard-of-care regimen of currently available checkpoint inhibitors.

In preclinical models, treatment with THIO followed by pembrolizumab led to highly potent anticancer effects compared with pembrolizumab alone in patients with SCLC. THIO converts SCLC tumors that are immunologically cold and non-responsive into those deemed hot and responsive to pembrolizumab.

Then in combination with atezolizumab, THIO was highly synergistic and effective and resulted in a complete regression of aggressive HCC tumors. In HCC, the combination of ionizing radiation and atezolizumab was just partially efficacious, according to a cell-based model. Additionally, THIO was highly synergistic and curative with atezolizumab in a preclinical model of colorectal cancer.

Now, a multicenter, open-label, phase 2 trial will evaluate THIO administered in sequence with anti-PD-1 or anti-PD-L1. The trial will use an innovative basket/umbrella design and is made up of 4 baskets, including SCLC, liver cancer, colorectal cancer, and solid tumors.

In the first basket of patients with SCLC, THIO will be added to the current standard of care, EP plus atezolizumab. In the other 3 arms, THIO will be given in combination with atezolizumab or pembrolizumab.

The main goal of part A of study is to select the best combination by tumor type to expand into part B. Then, part B will include multiple phase 2 pivotal arms seeking accelerated approvals.

As of now, the THIO-102 trial is on track to begin enrolling patients later this year.

“These are patients that are facing very limited treatment options, usually chemotherapy with minimal efficacy and high toxicity,” said Vlad Vitoc, MD, chairman and chief executive officer of MAIA, in the press release. “THIO sequenced with an immune checkpoint inhibitor has demonstrated complete tumor regression in several cancer preclinical models. We are very confident THIO can substantially improve on the limited clinical efficacy shown so far by atezolizumab, pembrolizumab and others. This go-to-market trial-THIO 102-may provide THIO with more than 9 additional indications. Our existing trial with non–small cell lung cancer is another indication, potentially giving THIO more than 10 indications in total. Most oncology compounds at this stage of development have only one. We have 10 shots on goal.”

REFERENCE:

MAIA biotechnology’s telomere-targeting agent THIO, in combination with checkpoint inhibitor immune therapies atezolizumab (anti-PD-L1) or pembrolizumab (anti-PD-1), demonstrated significantly greater tumor inhibition. News release. February 13, 2023. Accessed February 14, 2023. https://bwnews.pr/3IqeUfz