On November 13, 2025 Synthekine Inc., an engineered cytokine therapeutics company, reported that the company has dosed the first patient in the SYNERGY-101 study. SYNERGY-101 is a global, randomized Phase 2 clinical trial evaluating STK-012 combined with pembrolizumab and chemotherapy (PCT) vs. PCT in first-line, PD-L1 negative nonsquamous non-small cell lung cancer (NSCLC).

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"This marks a key milestone for Synthekine as we advance STK-012 into a randomized Phase 2 trial," said Debanjan Ray, Chief Executive Officer of Synthekine. "Our promising Phase 1b data suggest that STK-012 may lead to a meaningful improvement in outcomes in PD-L1 negative NSCLC, a population with limited benefit from current therapies."

Positive Phase 1b results presented at SITC (Free SITC Whitepaper) 2025 showed a 50% response rate in PD-L1 negative nonsquamous NSCLC patients treated with STK-012 in combination with PCT, substantially higher than the 23–32% response typically seen with standard of care alone. Notably, similarly high response rates were observed in patients with immune-resistant tumor profiles, such as those patients with STK11 or KEAP1 mutations, which have a high prevalence in PD-L1 negative NSCLC.

"PD-L1 negative patients represent 30-40% of new nonsquamous NSCLC diagnoses and typically face poor prognosis on standard-of-care therapy, highlighting the need for new treatment options in this setting," said Naiyer Rizvi, M.D., Chief Medical Officer of Synthekine. "SYNERGY-101 will help determine whether STK-012 can offer a new standard of care for this underserved population."

For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT05098132.

About SYNERGY-101

SYNERGY-101 is a global, randomized Phase 2 study designed to evaluate the safety and efficacy of STK-012 in combination with PCT in first line, PD-L1 negative nonsquamous NSCLC patients. This trial aims to enroll approximately 105 patients, with a primary endpoint of overall response rate based on RECIST v1.1. Secondary endpoints include progression-free survival and safety.

About PD-L1 Negative Nonsquamous Non-Small Cell Lung Cancer

Lung cancer is the third-most common cancer in the United States and is a serious and life-threatening disease, which is expected to account for 20% of cancer deaths in 2025.1 Nonsquamous NSCLC is the most common form of lung cancer and PD-L1 negative patients account for 30 – 40% of these patients, who have a poor prognosis despite currently available standard-of-care therapies.

1Cancer Facts & Figures 2025, American Cancer Society (ACS), Atlanta, Georgia, 2025

About STK-012

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, while minimizing activation of other lymphocytes, such as natural killer (NK) cells or naïve T cells, which are associated with IL-2 related toxicity.

(Press release, Synthekine, NOV 13, 2025, View Source [SID1234659944])