On October 7, 2021 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported that it will be presenting design and rationale details of a Phase 1 trial (KN-8701: NCT04913285) evaluating KIN-2787 during the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Kinnate Biopharma, OCT 7, 2021, View Source [SID1234590929]).
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KIN-2787, Kinnate’s most advanced product candidate, is an orally available small molecule pan-RAF inhibitor being developed for the treatment of patients with lung cancer, melanoma, and other solid tumors. KIN-2787 has been designed to target both monomeric and dimeric forms of the mutant BRAF kinase and minimize paradoxical activation, a liability often observed with other RAF inhibitors that can adversely impact tolerability and require addition of a MEK inhibitor to suppress pathway activation. Unlike currently available treatments that target only Class I BRAF kinase mutations, KIN-2787 targets Class II and Class III BRAF alterations, where it has the potential to be a first-line targeted therapy, in addition to covering Class I BRAF mutations. In pre-clinical studies, KIN-2787 has shown favorable pharmaceutical properties, achieves substantial systemic exposures in toxicology studies and induces regressions in human cancer xenograft models driven by BRAF Class I, II or III alterations.
"Approved BRAF inhibitors have limited clinical activity in diverse solid tumors driven by BRAF Class II or III alterations, highlighting the urgency to develop effective next-generation targeted therapies for these patients who currently have limited options," said the trial’s co-investigator and presenter Meredith McKean, MD, MPH, Associate Director, Melanoma and Skin Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology. "We are pleased to share additional details of this two-part trial with this year’s conference attendees."
KN-8701 (NCT04913285) is a first-in-human, multicenter, non-randomized, open-label, Phase 1 trial of KIN-2787 in adult patients with BRAF mutant advanced and metastatic solid tumors (AMST). KIN-2787 is given orally bid continuously in 28-day cycles until drug intolerance or disease progression. Planned sample size is approximately 115 patients in two parts: Part A is a trial of dose-escalation to maximum tolerated dose open to patients with AMST driven by BRAF Class I, Class II or Class III genomic alterations. Part B will evaluate a selected dose of KIN-2787 in three cohorts of patients with melanoma, NSCLC, or other AMST, each driven by BRAF Class II or Class III alterations. Standard Phase 1 enrollment criteria are required, and key exclusion criteria include known clinically active brain metastases from non-brain tumors, and prior receipt of BRAF-, MEK-, or MAPK-directed inhibitor therapy (except for cases in which these inhibitors were used in FDA-approved indications).
"We are pleased with the progress of this first-in-human trial of KIN-2787 and grateful to all the trial participants. With poorer prognosis observed in NSCLC and melanoma patients harboring tumors driven by BRAF Class II or III alterations, there is a dire need for more effective and better tolerated therapies," said Richard Williams, MBBS, Ph.D., Chief Medical Officer of Kinnate. "We are proud to collaborate with the Sarah Cannon Research Institute and all the other sites participating in this important trial."
The KN-8701 trial is currently recruiting across three centers in the United States. For more information, please visit www.kinnate.com/patients.
The poster (#P226), titled "Design and rationale of a first in human (FIH) Phase 1/1b study evaluating KIN-2787, a potent and highly selective pan-RAF inhibitor, in adult patients with BRAF mutation positive solid tumors," was presented by Dr. McKean and can be accessed online at: View Source