In short
STK-012 is an investigational immunotherapy being studied in a Phase 2 clinical trial for people with advanced non-small cell lung cancer (NSCLC). The trial, NCT05098132, is testing STK-012 alone and in combination with other cancer treatments in 134 participants. STK-012 is a first-in-class α/β IL-2 receptor biased partial agonist designed to stimulate the immune system against tumours while avoiding the toxicities typically seen with IL-2 therapies.
Key points
- STK-012 is an investigational α/β IL-2 receptor biased partial agonist, a new type of immunotherapy.
- The main trial is a Phase 2 study in advanced non-small cell lung cancer (NSCLC).
- The trial plans to enrol 134 participants and is currently authorised.
- STK-012 is given as a subcutaneous injection and is being tested alone and with pembrolizumab, pemetrexed, and carboplatin.
- The primary measure is the objective response rate (ORR), which looks at how many people's tumours shrink or disappear.
- Early Phase 1 results reported no capillary leak syndrome or cytokine release syndrome, with nausea, fatigue, and rash as the most common side effects.
What is STK-012?
STK-012 is an investigational immunotherapy, meaning it is not yet approved as a medicine. It is described as a first-in-class α/β IL-2 receptor biased partial agonist. This means it is the first drug of its kind designed to stimulate a specific part of the immune system — the interleukin-2 (IL-2) receptor — in a selective way. The substance is being developed for the treatment of advanced non-small cell lung cancer (NSCLC), a type of lung cancer.
How does STK-012 work?
STK-012 works by selectively stimulating CD25-positive antigen-activated T-cells, which are immune cells that have been triggered to recognise and attack cancer cells. By targeting the α/β form of the IL-2 receptor, STK-012 aims to drive antitumor activity while sparing the broad activation of other immune cells such as natural killer (NK) cells. This selective approach is intended to avoid the hallmark toxicities associated with traditional IL-2 therapies, such as capillary leak syndrome (CLS) and cytokine release syndrome (CRS).
Which conditions is it studied for?
- Non-small cell lung cancer (NSCLC) — the main condition studied in the Phase 2 trial, specifically advanced or metastatic NSCLC.
The Phase 2 trial focuses on people with non-squamous NSCLC who have not received prior treatment and whose tumours show low PD-L1 expression (less than 1%) or carry an STK11 mutation. These patients typically derive modest benefit from standard chemo-immunotherapy, which is why STK-012 is being tested in this group.
How is STK-012 given?
STK-012 is given as a subcutaneous injection, meaning it is injected under the skin. In the Phase 2 trial, the dose being tested is 2.25 mg given subcutaneously. In the earlier Phase 1a/1b study, STK-012 was administered subcutaneously every three weeks (Q3W) in combination with standard of care pembrolizumab, pemetrexed, and carboplatin.
What do the clinical trials show?
One clinical trial is registered for STK-012 in the EU Clinical Trials Information System. The Phase 2 trial (NCT05098132) is authorised and plans to enrol 134 participants with advanced non-small cell lung cancer. The trial is interventional and compares the objective response rate (ORR) in people with first-line non-squamous NSCLC (PD-L1 less than 1% or STK11 mutation) treated with STK-012 2.25 mg plus pembrolizumab, pemetrexed, and carboplatin (PCT) versus PCT alone.
The primary outcome measure is the objective response rate (ORR), which is the proportion of participants with a confirmed complete response (CR) or confirmed partial response (PR) as assessed by blinded independent central review (BICR). In other words, ORR measures how many people experience significant tumour shrinkage or disappearance of their cancer.
Who can take part in the phase 2 trial?
The Phase 2 trial enrols people with treatment-naïve, stage IV non-squamous NSCLC without actionable genetic alterations (AGAs). Specifically, the trial focuses on participants whose tumours have PD-L1 expression below 1% or carry an STK11 mutation. These are people who have not yet received treatment for their advanced disease.
What side effects are known?
In the Phase 1a/1b study, the most frequent treatment-related adverse events (TRAEs) were nausea (44% all grades, 0% grade 3), fatigue (40% all grades, 4% grade 3), and rash or dermatitis (40% all grades, 16% grade 3). One grade 4 TRAE was reported, a decrease in absolute neutrophil count (ANC), a type of white blood cell important for fighting infections. No grade 5 adverse events (deaths), dose-limiting toxicities (DLTs), or discontinuations due to treatment-related adverse events were reported. Importantly, no cases of capillary leak syndrome or cytokine release syndrome were observed, which are serious side effects commonly associated with traditional IL-2 therapies.