On May 26, 2022 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 the presentation of the design and rationale of a Phase 1 trial-in-progress (KIN-4802, NCT05242822) evaluating the Company’s pan-FGFR inhibitor product candidate, KIN-3248 (Press release, Kinnate Biopharma, MAY 26, 2022, View Source [SID1234615091]). The details will be presented during a poster session on June 6, 2022, at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) taking place in Chicago, IL, June 3-7.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"A major limitation of approved and clinical-stage FGFR treatments is the emergence of secondary, on-target resistance mutations that reduce duration of response, highlighting the urgency to further research and develop more efficacious next-generation therapies for these patients," said the trial’s co-investigator and presenter Lipika Goyal, MD, a faculty member in Gastrointestinal Medical Oncology at Mass General Cancer Center. "We are pleased to share additional details of this two-part Phase 1 trial-in-progress evaluating KIN-3248 at this year’s ASCO (Free ASCO Whitepaper) conference."

KIN-3248 is an irreversible, small molecule pan-FGFR inhibitor designed to address primary FGFR2 and FGFR3 oncogenic alterations, and those predicted to drive acquired resistance to current FGFR-targeted therapies, including gatekeeper, molecular brake, and activation loop mutations observed in cancers such as intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC). In preclinical studies, KIN-3248 demonstrated inhibitory activity across a wide range of clinically relevant mutations that drive primary disease and acquired resistance to other FGFR inhibitors.

The KN-4802 clinical trial (NCT05242822) is a multi-center, open-label, two-part study of approximately 120 patients to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-3248 in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. The dose escalation portion (Part A) of the trial will determine the recommended dose and schedule of KIN-3248 for further evaluation in patients with FGFR2 and/or FGFR3 gene alteration-driven cancers. The dose expansion phase (Part B) of the trial will assess the safety and efficacy of KIN-3248 at the recommended dose and schedule in FGFR inhibitor naïve and FGFR inhibitor pretreated patients with cancers driven by FGFR2 and/or FGFR3 gene alterations, including ICC, UC, and other selected adult solid tumors. This trial is currently enrolling across multiple sites in the United States.

"Unfortunately, acquired resistance to FGFR inhibitors frequently emerges during therapy for patients with FGFR-driven cancers, creating an urgent need to develop more effective and durable targeted therapies for these patients," said Richard Williams, MBBS, Ph.D., Chief Medical Officer of Kinnate. "We are pleased with the recent initiation of this first-in-human trial of KIN-3248, in collaboration with Mass General Cancer Center and other participating sites, and are grateful to the patients and physicians involved, without whom this research would not be possible."

In addition, in an abstract published in the ASCO (Free ASCO Whitepaper) meeting proceedings, the Company also shared updates from its preclinical in vitro and in vivo preclinical studies evaluating KIN-2787 in combination with binimetinib. In these studies, KIN-2787 demonstrated significant combination benefit in NRAS-mutant melanoma models. Taken together with its unique selectively, these data support the use of KIN-2787 in combination therapy in this patient segment. Melanoma tumor cell lines bearing NRAS Q61 alterations demonstrated synergistic benefit with KIN-2787 combined with binimetinib. Daily KIN-2787 plus binimetinib treatment in NRAS-altered melanoma xenograft models resulted in significant tumor growth inhibition benefit relative to either agent alone and was associated with added MAPK pathway biomarker suppression. A Phase 1/1b dose escalation and expansion clinical trial evaluating the safety and efficacy of KIN-2787 is ongoing (NCT04913285).

Abstracts accepted for the ASCO (Free ASCO Whitepaper) Annual Meeting include:

For additional information, visit the ASCO (Free ASCO Whitepaper) Annual Meeting webpage: View Source

Kinnate will also host an exhibit at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting at booth number 3047.