Synthekine's STK-012 Shows Major Promise in Hard-to-Treat Lung Cancer

MENLO PARK, CA – April 21, 2026 – Biotechnology firm Synthekine has unveiled striking new data for its investigational cancer drug, STK-012, suggesting a potential breakthrough for some of the most challenging forms of lung cancer. In a presentation at the American Association for Cancer Research (AACR) Annual Meeting 2026, the company reported that its precision cytokine therapeutic, when added to standard chemoimmunotherapy, produced robust responses in patients whose tumors are typically resistant to treatment.

The updated results from a Phase 1 study focus on patients with first-line non-squamous non-small cell lung cancer (NSCLC), a population that often faces a grim prognosis. The data, presented by Dr. Salman Punekar of NYU Langone Health, showed significant anti-tumor activity, particularly in patient subgroups known for their resistance to current therapies, offering a new glimmer of hope in a difficult-to-treat setting.

A New Approach for 'Immune-Cold' Tumors

For years, the standard of care for patients with advanced NSCLC without specific genetic mutations has been a combination of chemotherapy and immune checkpoint inhibitors, such as Merck's Keytruda (pembrolizumab). While this chemoimmunotherapy approach has transformed outcomes for many, a substantial number of patients derive limited benefit. This is especially true for those with tumors that do not express the PD-L1 protein, a key biomarker for immunotherapy response.

These so-called "immune-cold" tumors are notoriously difficult to treat because they lack the pre-existing immune activity that checkpoint inhibitors are designed to unleash. This group includes tumors with loss-of-function mutations in genes like STK11 and KEAP1, which are found in a significant subset of NSCLC patients and are associated with an aggressive disease course and poor response to standard treatments. Historical data from pivotal trials like KEYNOTE-189 show that while chemoimmunotherapy is beneficial, the objective response rates (ORR) for PD-L1-negative patients hover around 32%. For patients with STK11/KEAP1 mutations, the outlook is even more dire, with response rates often falling between 7% and 15% and median survival under seven months.

This is the critical unmet need Synthekine aims to address with STK-012.

Impressive Results in a Resistant Population

The data presented at AACR 2026 provides a compelling case for STK-012's potential. In an efficacy-evaluable group of 36 patients, nearly all of whom were PD-L1-negative, the combination of STK-012 with pembrolizumab and chemotherapy achieved an impressive 50% objective response rate and a 97% disease control rate. This figure significantly surpasses the historical benchmarks for standard care in this population.

The results were even more pronounced in the most resistant subgroups. Among 18 patients with STK11, KEAP1, and/or SMARCA4 mutations, the therapy delivered a 61% ORR and a 100% disease control rate. For the notoriously difficult-to-treat subgroup with STK11/KEAP1 co-mutations (8 patients), the combination achieved a 50% ORR. Furthermore, median progression-free survival in this co-mutated group was 5.5 months, with a median overall survival that has not yet been reached after nearly seven months of follow-up—a stark contrast to the 5-7 month median survival typically seen with standard therapy.

“These data underscore the potential for STK-012 to improve outcomes for some of the hardest-to-treat patients with lung cancer,” said Naiyer A. Rizvi, M.D., Chief Medical Officer of Synthekine, in a statement. “The response rates and early durability signals we are seeing, together with compelling translational evidence of targeted T‑cell activation, establish a strong case that STK-012 can overcome the immune resistance that has historically limited outcomes in this population.”

Importantly, the addition of STK-012 was generally well-tolerated. Across 39 safety-evaluable patients, there were no dose-limiting toxicities and no patients had to discontinue the drug due to side effects. The most common adverse events, such as rash, nausea, and fatigue, were manageable and reversible.

Precision Engineering to Redefine Cytokine Therapy

STK-012 represents a new generation of cytokine therapies. It is a first-in-class, engineered version of Interleukin-2 (IL-2), a powerful immune-signaling protein. While high-dose IL-2 was one of the earliest forms of immunotherapy, its use has been limited by severe, life-threatening toxicities caused by its broad activation of the immune system.

Synthekine's drug is designed for precision. As an α/β IL-2 receptor-biased partial agonist, it selectively stimulates the antigen-activated T cells responsible for killing cancer cells, while avoiding the broad activation of other immune cells, like natural killer (NK) cells, that are linked to IL-2's harsh side effects.

Translational data from the study supports this targeted mechanism. STK-012 led to a robust expansion of activated CD8+ T cells and a strong induction of IFN-γ, a key cytokine in anti-tumor immunity. Crucially, this occurred with minimal induction of inflammatory cytokines like IL-6 and TNF-α, which are associated with toxicity. The data also showed that STK-012 could reinvigorate exhausted T cells and drive clonal T cell expansion, even within the suppressive microenvironment of STK11/KEAP1 co-mutated tumors.

“Our translational data suggest that STK-012 can work synergistically with immune checkpoint inhibitors to help re-engage antitumor immunity and enable functional T-cell responses in these tumors,” stated Martin Oft, M.D., Chief Scientific Officer of Synthekine.

The Path Forward: Collaboration and Clinical Trials

With these encouraging Phase 1 results in hand, Synthekine is moving forward with a larger, more definitive study. The company is actively enrolling patients in SYNERGY-101, a global, randomized Phase 2 clinical trial. This study will directly compare STK-012 plus chemoimmunotherapy against the current standard of care—chemoimmunotherapy alone—in first-line, PD-L1-negative non-squamous NSCLC patients.

The trial is being conducted under a collaboration and supply agreement with Merck, which provides Keytruda for use in the study. This partnership between a nimble biotech and a pharmaceutical giant is crucial for accelerating the development of promising new therapies. While Merck provides the Keytruda, Synthekine, a well-funded private company with over $396 million raised to date, retains all commercial rights to STK-012.

The results of the SYNERGY-101 trial will be critical in confirming the early promise of STK-012 and determining if this novel agent can finally change the treatment paradigm for a large population of lung cancer patients who desperately need better options.