BRAF V600E x BTK

It was an extraordinarily busy week for clinical trial news and updates due to several prominent international conferences. Here’s a look at some of the highlights. Moderna announced that its Omicron-containing COVID-19 booster candidate, mRNA-1273.214 demonstrated superior antibody response against Omicron in its Phase II/III study. The vaccine contains the original COVID-19 vaccine, Spikevax, as well as a vaccine targeting the Omicron variant. In the study, the 50-microgram booster dose of the bivalent vaccine hit all pre-specified endpoints, including superior neutralizing antibody against the Omicron variant one month after dosing compared to the original Spikevax vaccine. The dose of the bivalent vaccine was generally well-tolerated, with side effects similar to what was seen with the original Spikevax shots. The company also announced it had dosed the first patients in a Phase III trial of its seasonal influenza vaccine candidate, mRNA-1010. It is expected to enroll about 6,000 adults in the Southern Hemisphere. It is designed to evaluate the safety and immunological non-inferiority of the mRNA flu shot compared to a licensed seasonal flu vaccine in adults 18 years and older. BioNTech presented preliminary Phase I data of its BNT122 it is evaluating with Genentech in pancreatic cancer. The Phase I trial is studying the mRNA-based individualized neoantigen specific immunotherapy (iNeST) autogene cevumeran (BNT122) in combination with Genentech’s Tecentriq (atezolizumab), an anti-PD-L1 immune checkpoint inhibitor, and chemotherapy. The patients in the study have resected pancreatic ductal adenocarcinoma (PDAC). The early data demonstrated a favorable safety pro encouraging indications of clinical activity. BNT122 is being developed in multiple solid tumor indications. Eli Lilly and Boehringer Ingelheim presented data at the American Diabetes Association Scientific Sessions 2022 in New Orleans, suggesting their Jardiance (empagliflozin) demonstrated a decreased risk of hospitalization for heart failure by 50%. The two companies presented data from two analyses of the final U.S. data from the EMPagliflozin Comparative Effectiveness and Safety (EMPRISE) real-world study. The results demonstrated Jardiance reduced the risk of hospitalization for heart failure compared to two other classes of glucose-lowering drugs in adults with type 2 diabetes. It showed relative risk decreases of 50% compared to DPP-4 inhibitors and 30% compared to GLP-1 receptor agonists. Novartis announced that Tafinlar (dabrafenib) + Mekinist (trametinib) significantly improved efficacy in patients ages 1 to 17 years old with BRAF V600 pediatric low-grade glioma (pLCC) requiring first systemic treatment compared to chemotherapy. The combination are BRAF/MEK inhibitors. Enterome announced proof-of-concept immune response data and first clinical data from its Phase I/II trial of EO2401 in combination with BMS’s Opdivo in non-resectable adrenocortical carcinomas (ACC), treated with at least one line, but not more than two previous lines of systemic therapy, or without prior systemic therapy for advanced/metastatic disease. EO2401 is a first-in-class off-the-shelf OncoMimics immunotherapy combining three OncoMimics peptides closely mimicking IL13Ra2, BIRC5 and FOXM1. Gilead Sciences presented data from the Phase III TROPiCS-02 trial of Trodelvy (Sacituzumab govitecan-hziy) in heavily pre-treated HER+/HER2- metastatic breast cancer patients. It hit the primary endpoint of progression-free survival, showing a 34% reduction in the risk of disease progression or death. Janssen presented Phase III data of Imbruvica (ibrutinib) in lymphoma. The drug is a Bruton tyrosine kinase inhibitor. It reduced the risk of disease progression by 25% when combined with bendamustine-rituximab and rituximab in patients with newly diagnosed mantle cell lymphoma. ImmunityBio announced new positive results from the pivotal Phase II/III study for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (QUILT 3032) and Phase II trial in advanced pancreatic cancer (QUILT 88). The data supported the company’s approach to activating NK cells and T cells for difficult-to-treat cancers. Jazz Pharmaceuticals announced positive data from a Phase II/III study developed with the Children’s Oncology Group (COG). They evaluated the intramuscular administration of Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) in adult and pediatric patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) who developed hypersensitivity to an E. coli-derived asparaginase. The data confirmed the interim analysis presented in December 2021. It demonstrated that greater than 90% of patients in Cohort 1c receiving the IM dose three days per week hit nadir serum asparaginase activity (NSAA) levels greater than or equal to 0.1 IU/mL at 48 and 72 hours. Moderna dosed the first participants in a Phase III trial of its seasonal influenza vaccine candidate, mRNA-1010. It is expected to enroll about 6,000 adults in countries in the Southern Hemisphere. Biohaven Pharmaceutical presented 31 abstracts, including three late-breakers and three oral presentations at the AHS meeting. The showcase was full Phase III data for zavegepant nasal spray as an acute treatment for migraine. It also presented data from a 52-week open-label extension study of Nurtec (ODT) (rimegepant) of every other day preventive treatment of migraine and as an as-needed acute treatment. Zavegepant is a third-generation, high affinity, selective and structurally unique, small molecule CGRP receptor antagonist. In a Phase II/III trial with more than 1000 patients receiving the drug, it demonstrated statistical superiority to placebo on the co-primary endpoints of 2-hour freedom from pain and freedom from a patient’s most troublesome symptoms, either nausea, photophobia or phonophobia. The Nurtec study demonstrated that the drug was safe and effective and helped almost half of the patients achieve a 100% reduction in monthly migraine days.