KFA115 / Novartis - LARVOL DELTA

KFA115: A first-in-class selective IKZF2 (Helios) and IKZF4 (Eos) molecular glue degrader for immuno-oncology (ACS-Fall 2026) - "We recently disclosed DKY709, a first-generation IKZF2/4 degrader that operates via a Cereblon E3 ligase-mediated degradation mechanism, and this compound has been explored in human clinical trials for its immunomodulatory potential. Interestingly, some cardiac effects observed with early Helios degraders were not solely attributable to hERG inhibition, which led to the implementation of an in vitro screening flowchart to identify and mitigate cardiac liabilities earlier in the drug discovery process. Through SAR optimization, we identified KFA115, a more potent and selective IKZF2 and IKZF4 degrader with improved cardiac safety profile, which has been evaluated in human clinical trials as an immunomodulatory drug."

Immuno-oncology • Targeted Protein Degradation • CRBN • IKZF1 • IKZF2

A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers (clinicaltrials.gov) - P1 | N=126 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=180 ➔ 126

Enrollment change • Enrollment closed • Anal Carcinoma • Breast Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Cutaneous Melanoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thymic Carcinoma • Thymus Cancer • Triple Negative Breast Cancer • BRAF • BRCA • MSI

A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Feb 2026 ➔ Sep 2027 | Trial primary completion date: Feb 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Anal Carcinoma • Breast Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Cutaneous Melanoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thymic Carcinoma • Thymus Cancer • Triple Negative Breast Cancer • MSI

A Study of Safety and Efficacy of KFA115 Alone and KFA115 in Combination With Tislelizumab in Patients With Select Advanced Cancers (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2025 ➔ Feb 2026 | Trial primary completion date: Sep 2025 ➔ Feb 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Anal Carcinoma • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Cutaneous Melanoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thymic Carcinoma • Thymus Cancer • MSI

A Study of Safety and Efficacy of KFA115 Alone and KFA115 in Combination With Tislelizumab in Patients With Select Advanced Cancers (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Anal Carcinoma • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Cutaneous Melanoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thymic Carcinoma • Thymus Cancer • MSI

A Study of Safety and Efficacy of KFA115 Alone and KFA115 in Combination With Tislelizumab in Patients With Select Advanced Cancers (clinicaltrials.gov) - P1 | N=220 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

Combination therapy • New P1 trial • Anal Carcinoma • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Cutaneous Melanoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thymic Carcinoma • Thymus Cancer • MSI