STK-012 / Synthekine - LARVOL DELTA

STK-012-101: Study of STK-012 Alone and With Other Treatments in Patients With Advanced Lung Cancer and Other Cancers (clinicaltrials.gov) - P1/2 | N=364 | Recruiting | Sponsor: Synthekine | Phase classification: P1 ➔ P1/2 | N=202 ➔ 364 | Trial completion date: Oct 2027 ➔ Jan 2029 | Trial primary completion date: Oct 2027 ➔ Jan 2029

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First Patient Dosed in SYNERGY-101, a Global, Randomized Phase 2 Clinical Trial of STK-012 in First-Line, PD-L1 Negative Nonsquamous Non-Small Cell Lung Cancer (Businesswire) - "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)."

Trial status • Lung Non-Squamous Non-Small Cell Cancer

Synthekine Presents Positive Initial Results from Phase 1a/1b Clinical Trial of STK-012 Plus Pembrolizumab and Chemotherapy in First-Line, PD-L1 Negative Nonsquamous Non-Small Cell Lung Cancer (Businesswire) - "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."

Late-breaking abstract • P1 data • Lung Non-Squamous Non-Small Cell Cancer

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 (SITC 2025) - P1 | "Memorial Sloan Kettering Cancer Center, New York, NY University of California, Los Angeles, Los Angeles, CA Yale Cancer Center, New Haven, CT The James Cancer Center, Ohio State University, Columbus, OH Dana Farber Cancer Institute, Boston, MA, Columbia University Irving Medical Center, New York, NY, Georgetown Lombardi Cancer Center, Washington, DC Northwell Health Center for Advanced Medicine NEXT Oncology Virginia, Fairfax, VA, HealthPartners, St. Paul, Minnesota Massachusetts General Hospital, Boston, MA NYU Grossman School of Medicine, New York, NY Duke Cancer Institute, Durham, NC Emory University, Atlanta, GA Baptist Cancer Center, Bartlett, Tennessee Northwest Medical Specialists, Tacoma, WA Hoag Family Cancer Institute, Newport Beach, CA Beverly Hills Cancer Center, Los Angeles, CA Providence Crosson Cancer Center, Fullerton, CA The University of Arizona Cancer Center, Tuscon, AZ Renovatio Clinical, Houston, TX Oncology Consultants, Houston, TX"

IO biomarker • Late-breaking abstract • P1 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL2 • IL2RA • ISG20 • KEAP1 • PD-L1 • SMARCA4 • STK11

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 (SITC 2025) - P1 | "Memorial Sloan Kettering Cancer Center, New York, NY University of California, Los Angeles, Los Angeles, CA Yale Cancer Center, New Haven, CT The James Cancer Center, Ohio State University, Columbus, OH Dana Farber Cancer Institute, Boston, MA, Columbia University Irving Medical Center, New York, NY, Georgetown Lombardi Cancer Center, Washington, DC Northwell Health Center for Advanced Medicine NEXT Oncology Virginia, Fairfax, VA, HealthPartners, St. Paul, Minnesota Massachusetts General Hospital, Boston, MA NYU Grossman School of Medicine, New York, NY Duke Cancer Institute, Durham, NC Emory University, Atlanta, GA Baptist Cancer Center, Bartlett, Tennessee Northwest Medical Specialists, Tacoma, WA Hoag Family Cancer Institute, Newport Beach, CA Beverly Hills Cancer Center, Los Angeles, CA Providence Crosson Cancer Center, Fullerton, CA The University of Arizona Cancer Center, Tuscon, AZ Renovatio Clinical, Houston, TX Oncology Consultants, Houston, TX"

IO biomarker • Late-breaking abstract • P1 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL2 • IL2RA • ISG20 • KEAP1 • PD-L1 • SMARCA4 • STK11

STK-012, a First-in-Class α/β IL-2 Receptor Biased Partial Agonist Enhances the Anti-Tumor Efficacy of Bispecific Antibodies (SITC 2025) - P1 | "Also, combination treatment of mSTK-012 with either PD1/VEGF BsAbs or BiTEs did not result in acute vascular toxicities.Conclusions Currently, STK-012 is in Phase I trials for first line Non-small cell lung cancer (NSCLC) patients (NCT05098132) in combination with pembrolizumab and chemotherapy. These findings highlight the potential of STK-012 to overcome key limitations of the next wave immunotherapies by selectively expanding and activating antigen-specific T cells while avoiding typical IL-2 systemic toxicities."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • FCGR2A • FCGR2B • IL2 • IL2RG

STK-012: A first-in-class alpha/beta IL-2 receptor biased partial agonist, in untreated metastatic non-small cell lung cancer (NSCLC) (ESMO 2025) - P1 | "In Parts E (phase Ia dose escalation, n= up to 10 per dose level) and F1 (phase Ib, PD-L1 negative [Tumor Proportion Score [TPS] <1%], dose expansion, n= up to 40) subjects with stage IV non-squamous (NSQ) NSCLC without actionable driver aberrations with approved therapies receive STK-012 subcutaneously Q3W in combination with first-line standard-of-care (SOC) pembrolizumab, carboplatin, and pemetrexed. Legal entity responsible for the study Synthekine. Funding Synthekine."

IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL2 • IL2RA • PD-L1

Synthekine Announces Late-Breaking Oral Presentation of Initial Clinical Data of STK-012 Plus Pembrolizumab and Chemotherapy in First-Line, PD-L1 Negative Nonsquamous NSCLC at SITC 2025 Annual Meeting (Businesswire) - "Results from an ongoing Phase 1a/1b to be presented at SITC. Company will also present new preclinical data on combinations of STK-012 with T cell engagers."

Late-breaking abstract • P1 data • Preclinical • Non Small Cell Lung Cancer

STK-012: “In the ongoing STK-012-101 study, monotherapy STK-012 showed a favorable safety profile and no DLTs at high, durable exposures, long T1/2, and PD profiles significantly improved from aldesleukin and non-α IL-2 analogues”; Solid tumors (Synthekine) - ICIS 2024: “Preliminary efficacy with monotherapy STK-012 (3 partial responses in Phase 1a) was observed in subjects who progressed on/after prior immunotherapy.”

P1 data • Oncology • Solid Tumor

T cell and immune activation from a phase 1 study of STK-012, a first-in-class IL-2R α/β selective partial agonist in advanced solid tumors (SITC 2024) - "These endpoints correlated with improved outcomes on study. STK-012 demonstrated a PK/PD profile which supports selectivity for antigen-activated T-cells and is distinct from that of aldesleukin and non-α-IL-2 analogues."

IO biomarker • Metastases • P1 data • Kidney Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD38 • CD8 • CXCL10 • IL2RA • IL5 • IL6 • ISG20

STK-012 Monotherapy and in Combination Therapy in Patients with Solid Tumors (clinicaltrials.gov) - P1 | N=202 | Recruiting | Sponsor: Synthekine | Trial completion date: Oct 2025 ➔ Oct 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2027

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Synthekine Announces Presentation of New Translational Data from Phase 1a/1b Clinical Trial of α/β Biased IL-2, STK-012, at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting (Businesswire) - P1a/1b | N=202 | NCT05098132 | Sponsor: Synthekine | "Synthekine Inc...presented positive translational results from the Phase 1a dose escalation portion of a Phase 1a/1b clinical trial...The Phase 1b dose expansion portion of the study in adults with advanced solid tumors remains ongoing (NCT05098132) and will include treating patients with STK-012 in combination with standard of care therapy in first line PD-L1 negative non-small cell lung cancer (NSCLC)....Results presented in the STK-012 poster at SITC include an analysis of key biomarkers, such as cytokine induction and memory CD8 T cell activation and expansion, both of which were found to correlate with best overall response (BOR). The poster also includes analysis of the TCR clonal expansion observed upon treatment with STK-012 monotherapy, which led to an 80-fold median increase in expanding TCR clones. TCR clonal expansion was found to correlate with both progression-free survival (PFS) and BOR in these patients."

P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

STK-012, a First-in-Class α/β IL-2 Receptor Biased Partial Agonist in Advanced Solid Tumors (KCRS 2024) - No abstract available

Metastases • Oncology • Solid Tumor • IL2

AACR: Synthekine hopes new IL-2 will be the high-alpha in a beta class (FierceBiotech) - "'The promise of IL-2 in the treatment of solid tumors has yet to be realized as IL-2 analogues developed to date have had limited efficacy and an unacceptable toxicity profile,' said Naiyer Rizvi...in a Tuesday statement."

Media quote

STK-012-101: STK-012 in advanced solid tumors (YouTube) - "Alexander Spira, MD...discusses findings from the Phase Ia/b STK-012-101 trial (NCT05098132) of STK-012, a novel α/β-IL-2R biased partial agonist, in advanced solid tumors. Manageable adverse events with no dose-limiting toxicities were observed and notable efficacy signals include partial responses in anti-PD-1 refractory non-small cell lung cancer (NSCLC), with ongoing dose expansion studies. STK-012 demonstrates distinct pharmacokinetic and pharmacodynamic profiles, supporting its selectivity for IL-2R α/β and warranting further investigation. This interview took place at American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, CA."

Interview • Video

Initial results from a phase 1a/1b study of STK-012, a first-in-class α/β IL-2 receptor biased partial agonist in advanced solid tumors (NCT05098132) (AACR 2024) - P1 | "During Phase 1a, subjects are enrolled in a 3+3 dose escalation to STK-012 as monotherapy (QW or Q3W) or STK-012 + pembrolizumab (Q3W) followed by Phase 1b expansions. Phase 1a and preliminary Phase 1b data are being presented for STK-012 monotherapy. In our ongoing Phase 1a/b trial, STK-012 demonstrated a favorable safety, PK, and PD profile which is distinct from that of aldesleukin and non-α IL-2 analogues. Peripheral PD and PK data support selectivity for IL-2R α/β. Preliminary monotherapy efficacy in subjects who are r/r to prior immunotherapy warrants further development."

Metastases • P1 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD8 • IFNG • IL2 • IL2RA • STAT5

Synthekine Presents Positive Initial Results from Phase 1a/1b Clinical Trial of α/β Biased IL-2, STK-012, for Treatment of Advanced Solid Tumors (Businesswire) - P1a/1b | N=202 | NCT05098132 | Sponsor: Synthekine | "Synthekine Inc...today announced positive initial results from a Phase 1a/1b clinical trial of its α/β biased IL-2 partial agonist, STK-012, for the treatment of advanced solid tumors....STK-012 is a first-in-class α/β-IL-2R biased partial agonist engineered to selectively stimulate CD25+ 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. In the results presented, which included 47 patients treated in Phase 1a dose escalation, STK-012 monotherapy demonstrated a favorable safety, efficacy, pharmacokinetic and pharmacodynamic profile....Enrollment to expansion cohorts in non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) are ongoing."

P1 data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Synthekine Announces Presentation of Initial Results from Phase 1a/1b Clinical Trial of STK-012 at AACR 2024 Annual Meeting (Businesswire) - "Synthekine Inc., an engineered cytokine therapeutics company, today announced that data from a Phase 1a/1b clinical trial of its α/β biased IL-2 partial agonist, STK-012, will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024...The company will also present new preclinical data for its orthogonal IL-2 (orthoIL-2) technology for cytokine-inducible cell therapies, currently being investigated in a Phase 1 study with the STK-009 + SYNCAR-001 combination therapy."

P1 data • Preclinical • Solid Tumor

Phase 1a/1b Study of STK-012 Monotherapy and in Combination With Pembrolizumab in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=202 | Recruiting | Sponsor: Synthekine | Phase classification: P1a/1b ➔ P1

Phase classification • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

First Patient Dosed in Phase 1b Clinical Trial of Synthekine’s α/β Biased IL-2, STK-012, for Treatment of Solid Tumors (Businesswire) - P1a/1b | N=202 | NCT05098132 | Sponsor: Synthekine | "Synthekine Inc...today announced that the company has completed phase 1a dose escalation and dosed the first patient in the Phase 1b portion of a clinical trial evaluating its α/β biased IL-2, STK-012, for the treatment of solid tumors....Synthekine recently completed the Phase 1a dose-escalation portion of the study in patients with various advanced solid tumors, with results suggesting a differentiated safety profile and monotherapy efficacy. The Phase 1b portion of the study will include dose expansion cohorts to evaluate STK-012 as monotherapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types, including renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC)."

P1 data • Trial status • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thoracic Cancer

First Patient Dosed in Phase 1b Clinical Trial of Synthekine’s α/β Biased IL-2, STK-012, for Treatment of Solid Tumors (Businesswire) - "'IL-2 is critical for T cell activation and promoting antitumor immunity,' said Naiyer Rizvi...'However, to date, no one has been able to unravel the pleiotropic nature of IL-2 and develop a drug that truly expands therapeutic index. STK-012 is built from unique insights into IL-2 biology and is the first α/β biased IL-2 with clinical results...'High-dose (HD) IL-2 has brought durable benefits to patients, even remissions for patients with metastatic melanoma and kidney cancer. But its significant toxicity and limited efficacy have prevented HD IL-2 from fulfilling its transformative potential in devastating cancers like non-small cell lung cancer,' said David McDermott..."

Media quote

First Patient Dosed in Phase 1b Clinical Trial of Synthekine’s α/β Biased IL-2, STK-012, for Treatment of Solid Tumors (Businesswire) - "Synthekine...announced that the company has completed phase 1a dose escalation and dosed the first patient in the Phase 1b portion of a clinical trial evaluating its α/β biased IL-2, STK-012, for the treatment of solid tumors....The Phase 1b portion of the study will include dose expansion cohorts to evaluate STK-012 as monotherapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types, including renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC)....The Phase 1b dose expansion portion of the clinical trial is an open-label, nonrandomized multi-center study currently enrolling patients....Results from the Phase 1a portion of the study will be presented at a future medical meeting."

Trial status • Non Small Cell Lung Cancer • Renal Cell Carcinoma

STK-012: An Engineered Selective IL2 Mutein That Promotes Anti-Tumor Responses without Related Toxicities (PEGS 2023) - "We have developed STK-012, an IL-2-agonist mutein selective for cells expressing the high affinity, trimeric IL-2 receptor (IL-2Ra/b/g) such as activated T cells. STK-012 preferentially stimulates tumor-specific T cells without significantly activating NK cells thus facilitating prolonged treatment without acute toxicity."

Oncology • IL2 • IL2RA

STK-012, an a/b-selective IL-2 activates tumor antigen specific CD25+ CD8 T cells to reject tumors without acute vascular toxicity (AACR 2023) - "Clinical trials with STK-012, a human α/β-IL-2 agonist, are in progress.1 Atkins, et al.; JCO 1999, 2 Dutcher, et al.; JITC 2014, 3 Liao, et al.; Immunity 2013, 4 Levin, et al.; Nature 2012, 5 Janku, et al.; Cancer Research 2021; 6 Diab, et al.; Cancer Disc. 2020"

Oncology • CD8 • FCGR2A • FCGR2B • IL2 • IL2RA • ISG20

Synthekine Secures $100 Million Series C Financing to Advance Pipeline of Engineered Cytokine Therapeutics (Businesswire) - "Synthekine Inc....announced the closing of a $100 million Series C financing led by The Column Group, with participation from both new and existing investors....Proceeds of the financing will be used to advance Synthekine’s differentiated therapeutic pipeline, led by its alpha/beta-biased IL-2 partial agonist, STK-012, which is currently in a Phase 1 clinical trial. In addition, it will support upcoming clinical studies of its orthogonal IL-2 and CD19 CAR-T combination therapy, STK-009 + SYNCAR-001, which the company anticipates to begin early this year. Funds will also be used to progress the company’s IL-12 partial agonist program, which is currently in IND-enabling studies."

Financing • New trial • Oncology • Solid Tumor