On November 7, 2025 Synthekine Inc., an engineered cytokine therapeutics company, reported positive initial results from a Phase 1a/1b clinical trial of STK-012 in first-line, PD-L1 negative nonsquamous (NSQ) non-small cell lung cancer (NSCLC) in combination with standard of care (SoC) pembrolizumab and chemotherapy (PCT). The data will be presented by Adam J. Schoenfeld, M.D., Memorial Sloan Kettering Cancer Center, New York, as a late-breaking oral presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2025 in National Harbor, MD, on Saturday, November 8.

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STK-012 is a first-in-class α/β-IL-2 receptor biased partial agonist engineered to selectively stimulate antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid broad stimulation of other lymphocytes, such as natural killer (NK) cells, which are associated with IL-2 toxicity.

STK-012 combined with SoC PCT demonstrated favorable safety and efficacy. The efficacy evaluable dataset (N = 21) included a highly immune resistant population with 17 subjects that were PD-L1<1% and 4 that were PD-L1 1% or greater; 15/21 subjects also had loss-of-function (LoF) tumor suppressor gene (TSG) mutations (STK11, KEAP1, and/or SMARCA4) or mucinous histology, features known to further limit response to SoC PCT.

"We set a high bar by enrolling first-line PD-L1 negative non-squamous NSCLC—a population marked by intrinsic immune resistance where standard-of-care therapies have consistently underperformed," said Naiyer Rizvi, M.D., Chief Medical Officer of Synthekine. "The high response rate observed with STK-012 in this setting is particularly encouraging and supports its potential to convert immune desert tumors into responders when added to SoC. STK-012’s unique selectivity for antigen-activated T cells, while sparing bystander lymphocytes, enables delivery of the critical IL-2 signal without the associated toxicity. These compelling data position STK-012 for advancement into a randomized Phase 2 trial."

The late-breaking oral presentation (Abstract Number: 1345), titled "Initial Phase 1a/1b Results of STK-012, an α/β IL-2 Receptor Biased Partial Agonist, with Pembrolizumab, Pemetrexed, and Carboplatin in 1L PD-L1 Negative Non-Squamous NSCLC" will be presented on November 8 at SITC (Free SITC Whitepaper) at 2:00 pm ET. The presentation will take place in the Potomac Ballroom at the Gaylord National Resort and Convention Center during the Clinical Oral Abstract session.

"Despite advances that have improved outcomes for newly diagnosed lung cancer patients, a significant unmet need persists — most notably among PD-L1 negative nonsquamous NSCLC and tumors with immune resistance mutations," said Dr. Schoenfeld. "Early STK-012 + SoC PCT data in these hard to treat populations are encouraging; if replicated in larger cohorts, they could reshape the treatment landscape."

Following the meeting, the presentation will be available on Synthekine’s website. For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT05098132.

STK-012 Initial Phase 1a/1b Data in Combination with Pembrolizumab + Chemotherapy

25 subjects were treated with STK-012 2.25 mg SC Q3W in combination with SoC pembrolizumab, pemetrexed, and carboplatin.

In 21 efficacy evaluable subjects (N=17 PD-L1<1%, N=3 PD-L1 1%, and N=1 PD-L1 5%), the ORR was 57% with STK-012 + SoC PCT.

In 17 PD-L1<1% subjects, the ORR was 53%, comparing favorably to 23 – 32% ORR expected with SoC PCT
In 10 subjects with at least 1 immune resistance mutation (STK11, KEAP1, SMARCA4), the ORR was 60%, comparing favorably to historical ORR of 7 – 33% with SoC PCT
In 5 subjects with mucinous histology, the ORR was 80%, comparing favorably to historical ORR of 21% with SoC PCT
In 25 safety evaluable subjects, the most frequent TRAEs were manageable and reversible nausea, fatigue, and rash/dermatitis. No subjects discontinued treatment with STK-012 due to TRAEs. No treatment-related hypotension, capillary leak syndrome, or cytokine release syndrome was observed.

(Press release, Synthekine, NOV 7, 2025, View Source [SID1234659660])