Dosing of KIN-3248 Begins in Advanced Solid Tumors With FGFR2 and/or FGFR3 Alterations

Partners | <b>Tennessee Oncology</b>

The first patient has been dosed in the phase 1 KN-4802 trial examining the safety, tolerability, and preliminary efficacy of KIN-3248 in adult patients with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations.

The first patient has been dosed in the phase 1 KN-4802 trial (NCT05242822) examining the safety, tolerability, and preliminary efficacy of KIN-3248, a next-generation pan-FGFR inhibitor, in adult patients with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations, according to a press release from Kinnate Biopharma Inc.1

KIN-3248 is an irreversible, small molecule pan-FGFR inhibitor developed for the treatment of intrahepatic cholangiocarcinoma (ICC), urothelial carcinoma (UC), and other solid tumors. The goal of the agent is to address FGFR2 and FGFR3 oncogenic alterations in these patients as well as drive resistance to current FGFR-targeted therapies, including gatekeeper, molecular brake, and activation loop mutation.

According to data from preclinical studies, KIN-3248 has demonstrated activity across a range of mutations which drive primary disease and acquired resistance to other FGFR inhibitors.

“Successfully treating intrahepatic cholangiocarcinoma and urothelial cancer patients with FGFR2 and/or FGFR3gene alteration–driven cancers remains a significant unmet need in cancer care,” added Benjamin Garmezy, MD, assistant director of Genitourinary Research at Sarah Cannon Research Institute, Tennessee Oncology, in the press release. “KIN-3248 brings a unique approach to potentially address the shortcomings of existing therapies in specific patient populations with primary FGFR2 and/or FGFR3 oncogenic alterations, including those patients with gatekeeper, molecular brake, and activation loop mutations.”

KN-4802 is a multicenter, open-label, 2-part, phase 1 trial which aims to enroll approximately 120 patients with advanced-stage solid tumors and known FGFR2 and/or FGFR3 alterations.2

The study will consist of 2 parts, dose-escalation and dose-expansion. Within part A, the dose-escalation portion of the trial, investigators will identify the recommended dose and schedule of KIN-3248 for this patient population. Part B, the dose-expansion phase of the trial, aims to examine the safety and efficacy of the agent. This part will investigate KIN-3248 at the recommended dose and schedule within patients with cancers driven by FGFR2 and/or FGFR3 alterations who were naïve to, or pretreated with, FGFR inhibitors.

Part B, the dose expansion phase, will assess these outcomes in inhibitor naïve and FGFR inhibitor pretreated patients with cancers driven by FGFR2 and/or FGFR3 gene alterations, including ICC, UC, and other specified adult solid tumors.

Primary end points within part A include incidence of dose limiting toxicities and incidence of adverse events with secondary end points including pharmacokinetics.

Part B of the trial includes the primary end points of objective response rate, disease control rate, duration of response, and progression-free survival in regard to maximum plasma concentration, time to reach maximum plasma concentration, and area under the plasma concentration.

Eligibility for enrollment is open to patients aged 18 and older with measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function. The study is actively recruiting patients who meet these requirement at study sites in Florida, Michigan, and Tennessee.

“With the dosing of the first patient in our phase 1 trial of KIN-3248, we are excited to further advance the development of this next-generation therapy, which we believe is unique among FGFR inhibitors and has the potential to offer a new targeted therapy option for cancer patients with FGFR-altered tumors,” Richard Williams, MBBS, PhD, chief medical officer of Kinnate Biopharma, Inc., stated in a press release.

References
  1. Kinnate Biopharma Inc. announces first patient dosed in phase 1 clinical trial of its FGFR inhibitor product candidate, KIN-3248. News release. Kinnate Biopharma, Inc. April 18, 2022. Accessed April 28, 2022. https://yhoo.it/38xReferences
  2. A study to evaluate KIN-3248 in participants with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. ClinicalTrials.gov. Updated April 5, 2022. Accessed April 28, 2022. https://bit.ly/3OITlYA