Merck KGaA announced an update on the Phase III INTR@PID Lung 037 study and the extensive INTR@PID clinical trial program for the potential first-in-class investigational bifunctional immunotherapy bintrafusp alfa, in difficult-to-treat cancers, including biliary tract cancer and cervical cancer. The comprehensive INTR@PID program is designed to assess the impact of bintrafusp alfa across distinct cancers and settings where TGF-ß is thought to play a driving role. TGF-ß is a cytokine that is known to be associated with tumor propagation and metastatic potential such as local immunosuppression, fibrosis, growth of tumor blood vessels and chemo- or radiotherapy resistance through several mechanisms. Trapping TGF-ß in the tumor microenvironment on top of PD-L1 blockade is thought to be transformative in different clinical settings. While reviewing the totality of data from the ongoing clinical trial INTR@PID Lung 037 in the first-line treatment of patients with stage IV non-small cell lung cancer that have high expression of PD-L1, the Independent Data Monitoring Committee recommended on January 19, 2021 to discontinue the clinical trial. Based on this recommendation, Merck KGaA, Darmstadt, Germany has made the decision to discontinue the clinical trial, as the study is unlikely to meet the co-primary endpoint, specifically progression-free survival. The recommendation by the Independent Data Monitoring Committee and the Company's decision is related only to this clinical trial. BTC: Topline results for the INTR@PID BTC 047 study are planned for Q1. Additionally,Phase II/III study of bintrafusp alfa in combination with chemotherapy as a first-line treatment for BTC (INTR@PID BTC 055), which is assessing a different hypothesis than the second-line monotherapy study, has completed enrollment in the Phase II portion and is on track for the Phase III portion. In 2020, the Japan Ministry of Health, Labour and Welfare granted SAKIGAKE 'fast-track' designation for bintrafusp alfa in BTC, a regulatory designation that enables an expedited review and is connected to indications with limited standards of care; Cervical Cancer: The Phase II cervical cancer study (INTR@PID CERVICAL 017) initiated in 2020 is currently ongoing with enrollment nearing completion. The study is evaluating bintrafusp alfa for the treatment of patients with advanced, unresectable cervical cancer that progressed during or after platinum-containing chemotherapy. Human papillomavirus (HPV) infection has been closely associated with increased TGF-ß expression in a variety of solid tumors, including cervical cancer.1 Encouraging efficacy of bintrafusp alfa in HPV-associated malignancies was reported from a pooled analysis of the Phase I (INTR@PID SOLID TUMOR 001) and a Phase II NCI-led trial.2 A new Phase I study in locally advanced/advanced cervical cancer as a combination therapy (INTR@PID CERVICAL 046) was also initiated in 2020; NSCLC: The bintrafusp alfa lung program is designed to assess the patient population that may benefit from the dual mechanism of action focusing on combination studies (INTR@PID LUNG 005, INTR@PID LUNG 024). In addition to studying combinations with standards of care, the INTR@PID LUNG 024 study will expand to include new combinations, including combining with VEGF inhibitors, CTLA-4 targeted immunotherapies, and PARP inhibitors; New Studies: Recently initiated monotherapy studies include a Phase II monotherapy study in patients with triple-negative breast cancer expressing high mobility group AT-hook 2 (HMGA2) (INTR@PID BREAST 020) and a Phase I monotherapy study in locally advanced/metastatic urothelial cancer (INTR@PID UROTHELIAL 152). A new Phase I multi-arm platform study combining bintrafusp alfa with GSK's iCOS (feladilimab) is initiating.