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According to the investigators, BBO-8520 represents a first-in-class approach to treating patients with previously treated KRASG12C-mutated metastatic non-small cell lung cancer (NSCLC).
The FDA granted fast track designation to BBO-8520 (BridgeBio Oncology Therapeutics) for the treatment of patients with previously treated KRASG12C-mutated metastatic non-small cell lung cancer (NSCLC).1 Currently, the treatment is undergoing evaluation in the ONKORAS-101 phase 1 clinical trial (NCT06343402).2
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BBO-8520 is an investigational oral therapy designed to inhibit the “on and off” state to provide optimal target coverage while addressing the amplification of KRASG12C and receptor tyrosine kinase activation, which are the 2 key mechanisms of adaptive resistant to current “off” state inhibitors. In multiple preclinical trials, BBO-8520 drove substantial tumor growth inhibition, even after emergence of resistance to sotorasib (Lumakras; Amgen), an FDA-approved “off” state inhibitor of KRASG12C.1
“NSCLC is among the most prevalent malignancies globally and there is a significant need for new precision oncology medicines to improve outcomes for patients in the metastatic setting. BBO-8520 promises to have a substantial impact in improving outcomes and prognosis for this group of patients,” said Benjamin Solomon, MBBS, PhD, professor and lead of lung medical oncology at the Peter MacCallum Cancer Center, in a news release.3
BBO-8520 is currently undergoing investigation in the first-in-human, open-label, multicenter phase 1a/1b clinical trial, ONKORAS-101 (NCT06343402), to assess its safety, tolerability, and pharmacokinetics as both a single agent therapy and in combination with pembrolizumab (Keytruda; Merck). According to the investigators, this trial consists of a dose escalation phase and dose expansion phase.2
Trial Name: Study of BBO-8520 in Adult Subjects with KRASG12C Non-small Cell Lung and Colorectal Cancer
ClinicalTrials.gov ID: NCT06343402
Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics
Completion Date (Estimated): February 2028
The study enrolled patients with KRASG12C-mutated NSCLC and colorectal cancer. Patients were enrolled if they had histologically documented locally advanced or metastatic, KRASG12C-mutated NSCLC, measurable disease by RECIST v1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1.2
For the dose escalation section of the study, patients were assigned to receive either oral BBO-8520 as a once-daily monotherapy (cohort 1a) or oral BBO once-daily with intravenous (IV) pembrolizumab (cohort 1b), with different dose levels of BBO-8520 being evaluated in both groups. For the dose expansion segment, patients will receive an assigned once-daily oral dose of BBO-8520 alone (cohort 2a) or with IV pembrolizumab (cohort 2b).2 According to the investigators, the first patients dosed with BBO-8520 in June 2024.3
Patients were excluded from the study based if they experienced the following: malignancy within the last 2 years (as specified by protocol); untreated brain metastases; or a known hypersensitivity to BBO-8520 or its excipients. For cohorts 2a and 2b, patients were excluded for the following reasons: known hypersensitivity to pembrolizumab or its excipients; active autoimmune disease or a history in which the disease may recur; and a history or interstitial lung disease or pneumonitis that required either steroids, or a current interstitial lung disease or pneumonitis.2
The primary end points for the study include incidence and severity of treatment-emergent adverse events (AEs) and serious AEs as well as dose-limiting toxicities, both of which will be assessed at about 3 years. Secondary end points include progression-free survival, duration of response, overall survival, and pharmacokinetics (eg, peak plasma drug concentration [Cmax], time to Cmax, and half life) of BBO-8520.2
“BBO-8520 represents a first-in-class approach with potential to address high unmet medical needs and shift the paradigm for cancer treatment,” Yong Ben, MD, chief medical and development officer of BridgeBio Oncology Therapeutics said in a news release. 1
