Calithera Biosciences, Inc. announced that updates related to the ongoing clinical programs for sapanisertib (CB-228) and mivavotinib (CB-659) will be presented at the upcoming International Association for Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC) and the 2022 Pan Pacific Lymphoma Conference, respectively. During the Pan Pacific Lymphoma Conference taking place July 18-22 in Koloa, Hawaii, Reem Karmali, MD, MS, associate professor of Medicine at Northwestern University, will present a poster detailing the trial design of Calithera's phase 2 study of mivavotinib, a spleen tyrosine kinase (SYK) inhibitor. The phase 2 trial (NCT05319028), which enrolled its first patient in June, is an open-label study of mivavotinib monotherapy in patients with relapsed/refractory non-GCB (ABC) diffuse large B-cell lymphoma (DLBCL).

The main objectives of the study are to confirm previously seen single-agent activity in non-GCB DLBCL patients, evaluate activity according to MYD88/CD79b mutational status, and refine dose/schedule in this patient population. Approximately 50 non-GCB DLBCL patients, with or without MYD88/CD79b mutations, will be randomized 1:1 to one of two oral dose/schedule cohorts: a continuous dosing schedule (100 mg QD) or an induction dosing schedule (120 mg QD x 14 days, then 80 mg QD starting Day 15). Data from this trial could position Calithera to initiate a study with registrational intent in biomarker-specific DLBCL populations.

During an August 9 mini oral session at IASLC/2022 WCLC, Jonathan W. Riess, MD, MS, director of Thoracic Oncology and associate professor at UC Davis Comprehensive Cancer Center, will present dose-escalation findings from a multi-center phase 1/2 investigator-initiated study evaluating sapanisertib, a potent and selective dual mTORC 1/2 inhibitor, in combination with telaglenastat (CB-839), a novel, investigational glutaminase inhibitor, in biomarker-defined cohorts of patients with advanced non-small cell lung cancer (NSCLC). Sapanisertib targets a key survival mechanism in tumors harboring NRF2 mutations, which are found in a considerable sub-population of patients across multiple solid tumor types and are generally associated with a poorer prognosis. In pre-clinical studies, combining sapanisertib and telaglenastat showed synergistic anti-tumor activity.

After evaluating five combination dosing levels in 13 patients, researchers determined that the sapanisertib/telaglenastat combination is safe and tolerable at the recommended expansion dose (2 mg sapanisertib once daily, 800 mg telaglenastat twice daily). Researchers also observed tumor shrinkage among the majority of evaluable patients (5/8), including patients with lung cancers harboring KEAP1 or NRF2 mutations. As a next step, study investigators plan to enroll patients into one of four expansion cohorts evaluating sapanisertib plus telaglenastat in squamous NSCLC with and without NRF2 or KEAP1 mutations, and adenocarcinoma NSCLC with KRAS and KEAP1 or NRF2 mutations.